History of 5 Bowen Road Essay

Look at any old photo of pre-1950 Hong Kong and the hillsides above the city were dotted with handsome verandah type homes like this one. From the Mid-levels up to The Peak, every successful European merchant, official, compradore or trader scrambled to put up a mansion befitting their perceived status in colonial society. This home was built in 1914 by the property company, Hongkong Land Investment and Agency Company Ltd. Its Devonian name ’Iddesleigh’ (pronounced ‘Idslee’) derived from the origins of its occupant, A Mr.  Mowbray Stafford Northcote secretary of the Hongkong Land Investment and Agency Company, who was an honorary correspondent to the magazine ‘Devonia’ and was related to the Earl of Iddesleigh. In common with many structures which were built on Hong Kong’s precipitous hillsides, the house stands on a handsome, terraced granite base. When built, the house would have had sweeping views across the harbour and its verandahs would have been open to the elements. Three-storey building built in neo-classical style, Corinthian columns, bow arch, decorated with carved eaves and rich ornate interior decoration, showing the lofty building owner socioeconomic status. The top of the building facade reflects its ornate pediment architectural style influenced by the Baroque. During the Japanese Occupation (1942-1945), this building was requisitioned as the home for the Japanese Imperial Naval commander. After liberation at the end of the Second World War, the house was occupied by the Royal Navy and it would later become the official residence of the senior RN officer in Hong Kong, the Commodore-in-Charge and has been better known as the â€Å"Commodore’s House† since 1952. In 1979, the building was handed over to the Hong Kong Government. In 1990, the building was allocated for charity Mother’s Choice Baby Nursing and residential special child care centers.

Facilitation of Conditioned Fear Extinction

Neuroscience 134 (2005) 247–260 FACILITATION OF CONDITIONED FEAR EXTINCTION BY D-CYCLOSERINE IS MEDIATED BY MITOGEN-ACTIVATED PROTEIN KINASE AND PHOSPHATIDYLINOSITOL 3-KINASE CASCADES AND REQUIRES DE NOVO PROTEIN SYNTHESIS IN BASOLATERAL NUCLEUS OF AMYGDALA Y. L. YANGa AND K. T. LUb* Institute of Biotechnology, Department of Molecular Biology and Biochemistry, National Chia-Yi University, 300 University Road, Chia-Yi, Taiwan b Department of Life Science, National Taiwan Normal University, 88 Ming-Chow Road, Sec 4, Taipei, Taiwan aKey words: extinction, D-cycloserine, MAPK, PI-3 kinase, amygdala. Abstract—Recent results showed that either systemic or intra-amygdala administration of D-cycloserine, a partial agonist at the glycine modulatory site on the glutamate N-methylD-aspartate receptor facilitates the extinction of conditioned fear. Here we evaluated the role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase in the basolateral nucleus of amygdala on the effect of D-cycloserine.The facilitation effect of D-cycloserine on fear extinction and mitogen-activated protein kinase activation was completely blocked by intra-amygdala administration of mitogen-activated protein kinase inhibitor PD98059 (500 ng/side, bilaterally) or U0-126 (20 M/side, bilaterally). Furthermore, phosphatidylinositol 3-kinase inhibitor (wortmannin, 5. 0 g/side, bilaterally) infused into the basolateral nucleus of amygdala signi? cantly reduced both facilitation effect of D-cycloserine and phosphatidylinositol 3-kinase activation.Intra-amygdala administration of a transcription inhibitor (actinomycin D, 10 g dissolved in 1. 6 l vehicle; 0. 8 l per side) and a translation inhibitor (anisomycin, 125 g dissolved in 1. 6 l vehicle; 0. 8 l per side) completely blocked the facilitation effect of D-cycloserine. Control experiments indicated the blockage by actinomycin D or anisomycin were not due to lasting damage to the basolateral nucleus of amygdala or state d ependency. In addition, none of the active drugs used here altered the expression of conditioned fear.These results suggested that phosphatidylinositol 3-kinase and mitogenactivated protein kinase-dependent signaling cascades and new protein synthesis within the basolateral nucleus of amygdala played important roles in the D-cycloserine facilitation of the extinction of conditioned fear.  © 2005 Published by Elsevier Ltd on behalf of IBRO. *Corresponding author. Tel: 886-2-29333149Ãâ€"234; fax: 886-229312904. E-mail address: [email  protected] ntnu. edu. tw (K. -T. Lu).Abbreviations: ACT DCS, actinomycin D D-cycloserine; ACT SAL, actinomycin D saline; ANI DCS, anisomycin D-cycloserine; ANI SAL, anisomycin saline; BLA, basolateral nucleus of the amygdala; CS, conditioned stimulus; DCS, D-cycloserine; EDTA, ethylenediaminetetraacetic acid; ISI, interstimulus interval; MAPK, mitogen-activated protein kinase; NMDA, N-methyl-D-aspartate; PD DCS, PD98059 D-cycloserine; PD SAL, PD9805 9 saline; PI-3K, phosphatidylinositol 3-kinase; US, unconditioned stimulus; U0 DCS, U0-126 D-cycloserine; U0 SAL, U0126 saline; VEH DCS, vehicle D-cycloserine; VEH SAL, vehicle saline; WH DCS, wortmannin D-cycloserine; WH SAL, wortmannin saline. 0306-4522/05$30. 00 0. 00  © 2005 Published by Elsevier Ltd on behalf of IBRO. doi:10. 1016/j. neuroscience. 2005. 04. 003 Fear conditioning occurs when a previously neutral stimulus (conditioned stimulus) is paired with an aversive stimulus (McAllister and McAllister, 1971).Following such pairing the conditioned stimulus is thought to elicit a state of conditioned fear. This is de? ned in animals by their behavior: freezing, autonomic reactivity, and fear-potentiated startle. A large literature indicates that the basolateral nucleus of the amygdala (BLA) is critically involved in both the acquisition and the expression of conditioned fear (Davis, 2000). Neurotoxic lesions or intra-amygdala infusion of glutamate antagonists into the BLA bl ocks the expression of conditioned fear. In addition, local infusion of N-methyl-D-aspartate (NMDA) speci? c antagonists blocks the acquisition of conditioned fear (Miserendino et al. , 1990; Kim et al. , 1991; Maren et al. , 1996; Gewirtz and Davis, 1997).Synaptic plasticity in this area is thought to underlie the learning process when afferent sensory information elicited by the conditioned stimulus is paired with afferent pain information elicited by the unconditioned stimulus (Fanselow and LeDoux, 1999). Extinction is de? ned as a reduction in conditioned fear when the conditioned stimulus (CS) is presented repeatedly in the absence of the unconditioned stimulus (US). Many studies show that extinction is not the result of forgetting or memory erasure but results from formation of new associations that compete with prior fear-conditioned associations (Falls and Davis, 1995; Davis et al. , 2000). Similar to acquisition, extinction is also blocked by glutamate NMDA receptor antagon ists either given systemically (Cox and Westbrook, 1994; Baker and Azorlosa, 1996; Kehoe et al. 1996) or locally infused into the BLA (Falls and Davis, 1992). The glycine modulatory site of the NMDA receptor provides a critical regulatory role. Whereas direct NMDA agonists may be neurotoxic due to unregulated calcium entry, partial agonists can facilitate glutamatergic NMDA activity in a more limited fashion (Lawler and Davis, 1992; Olney, 1994). Recent results showed that partial agonists acting at the glycine modulatory site of the NMDA receptor, such as D-cycloserine (DCS), enhance learning and memory in several animal models (Thompson and Disterhoft, 1997; Pussinen et al. , 1997; Matsuoka and Aigner, 1996; Land and Riccio, 1999; Walker et al. , 2002; 247 248 Y. L. Yang and K. T.Lu / Neuroscience 134 (2005) 247–260 extinction test, an extinction training and a post-extinction test (see Fig. 1A). Acclimation. On each of 3 consecutive days, rats were placed in the test chamb ers for 10 min and then returned to their home cages. Baseline startle test. On each of the next 2 consecutive days, animals were placed in the test chambers and presented with 30 95-dB startle stimuli at a 30-s interstimulus interval (ISI). Animals whose baseline startle response was 1% of the measurable level were not included in later analysis. Fear conditioning. Twenty-four hours later, rats were returned to the test chambers and after 5 min were given the ? rst of 10 light-footshock pairings.The shock (US) was delivered during the last 0. 5 s of the 3. 7 s light (CS). The average intertrial interval was 4 min (range 3–5 min) and the shock intensity was 0. 6 mA. Pre-extinction test. Twenty-four hours after fear conditioning, rats were returned to the test chambers and 5 min later presented with 30 startle-eliciting noise bursts (95 dB, 30 s ISI). These initial startle stimuli were used to habituate the startle response to a stable baseline prior to the light-noise test tr ials that followed. Thirty seconds later a total of 20 startle-eliciting noise bursts were presented, 10 in darkness (noise alone) and 10 3. 2 s after onset of the 3. s light (light-noise) in a balanced, irregular order at a 30-s ISI. Percent fear-potentiated startle was computed as [(startle amplitude on light-noise noise-alone trials)/noisealone trials] 100. Rats were then divided into equal size groups of comparable mean levels of percent fear-potentiated startle. Rats with less than 50% fear-potentiated startle during the pre-extinction test were not used. Extinction training. Extinction training (cue exposure) is de? ned as the repetitive exposure to the CS cue (light) in the absence of the US (shock). Twenty-four hours after the preextinction test, rats were returned to the test chamber. After 5 min, they were presented with 30, 3. s light exposures at a 30-s ISI. Context control groups (context exposure) remained in the test cages for the same amount of time but did not recei ve light presentations. Extinction training was performed for varying numbers of consecutive days (2 days for experiment 1 and 1 day for subsequent experiments). Post-extinction test-1. Twenty-four hours after the last extinction training, rats were returned to the test chamber. After 5 min, they were presented with 30 95-dB leader stimuli for a habituated startle baseline. This was followed by a total of 60 startle-eliciting noise bursts, 30 in darkness (noise alone) and 30 presented 3. 2 s after onset of the 3. s light (light-noise) in a balanced, irregular order at a 30-s ISI. Results were evaluated the same way as pre-extinction test. Post-extinction test-2. Twenty-four hours after the extend extinction training period, rats were returned to the test chamber and process the post-extinction test described above. Fear-potentiated startle test. Twenty-four hours after fear conditioning, rats were returned to the test chamber and testing for fear-potentiated startle using the post-e xtinction test-1 described above. Ledgerwood et al. , 2003; Richardson et al. , 2004). In addition, ( )-HA966, a competitive antagonist at the glycine regulatory site on the NMDA receptor, reversed the DCS effect (Walker et al. , 2002).Clinical studies have shown that DCS can sometimes enhance implicit memory and improve cognition in patients with Alzheimer’s disease (Schwartz et al. , 1996; Tsai et al. , 1998, 1999). It can also counter cognitive de? cits in schizophrenia (Javitt et al. , 1994; Goff et al. , 1999). Furthermore, systemic administration of DCS also proved to facilitate extinction of conditioned fear (Walker et al. , 2002; Ledgerwood et al. , 2003, 2004; Ressler et al. , 2004). Numerous signaling cascades including mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI-3K) and calcineurin, are involved in the extinction of conditioned fear (Lu et al. , 2001; Lin et al. , 2003).Similar mechanisms may also be involved in the facilitation effec t of DCS. This study was designed to clarify the relationship between amygdaloid NMDA receptors, MAPK and PI-3K signal cascades on the extinction of conditioned fear. EXPERIMENTAL PROCEDURES Animals Adult male Sprague–Dawley (SD) rats (obtained from the animal center of National Taiwan University Taipei, Taiwan) weighing between 250 and 350 g were used. Animals were housed in groups of four rats in a temperature (24  °C) -controlled animal colony with continuous access to food and water. Rats were kept on a 12-h light/dark cycle with lights on at 07:00 h. All behavioral procedures took place during the light cycle.All procedures were conducted in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals and the guidelines set forth by the Institutional Animal Care and Use Committee at the National Taiwan Normal University. In all experimental procedures involving animals, all efforts were made to minimize pain and the number of animals u sed. Surgery All surgeries were carried out under sodium pentobarbital (50 mg/ kg, i. p. ) anesthesia. Once anesthetized, the rat was placed in a Kopf stereotaxic instrument, the skull was exposed, and 22 gauge guide cannula (model C313G, Plastic-one Products, Roanoke, VA, USA) were implanted bilaterally into the BLA (AP, 2. ; DV, 9. 0, ML, 5. 0 from bregma (Paxinos and Watson, 1997)). Size 0 insect pins (Carolina Biological Supply, Burlington, NC, USA) were inserted into each cannula to prevent clogging. These extended about 2 mm past the end of the guide cannula. Screws were anchored to the skull and the assembly was cemented in place using dental cement (Plastic-one Products). Rats received an antibiotic (penicillin) once every day for the ? rst 3 days after the surgery to reduce the risk of infection. General behavioral procedures Fear conditioning was measured using the potentiated startle paradigm (Cassella and Davis, 1986; Lu et al. , 2001; Walker et al. , 2002).The rats were trained and tested in a startle chamber (San Diego Instruments, San Diego, CA, USA) in which cage movement resulted in the displacement of an accelerometer. Startle amplitude was de? ned as peak accelerometer voltage within 200 ms after startle stimulus onset. The behavioral procedures common to all experiments consisted of an acclimation phase, a baseline startle test phase, a fear conditioning phase, a pre- Drug injection DCS (Sigma) was freshly dissolved in saline. DCS (15 mg/kg, i. p. ) or saline was injected intraperitoneally 15 min prior to extinction training with a 26 gauge injection needle connected to a 1 ml syringe (Walker et al. , 2002; Ledgerwood et al. , 2003) (experiments 1– 8).MAPK inhibitor PD98059 (500 ng in 1 l of 20% DMSO; Calbiochem) (Lu et al. , 2001) or U0-126 (50 ng/side; Sigma) (Lin et al. , 2003) or 20% DMSO was infused into the BLA Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 249 Fig. 1. Systemic administration of DCS accelerate d extinction of conditioned fear. (A) Timeline of behavioral procedures for experiment 1. (B) Percent fear-potentiated startle measured 24 h before (pre-extinction test) and 24 h after extinction training (post-extinction test). Rats in each group were treated with either DCS or saline prior to a single session of extinction training. (C) To test for toxicity, after 24 h all animals of experiment 1 were retrained.They were tested for fear-potentiated startle response in the absence of drugs 24 h later (fear-potentiated startle test) (values are mean SEM, * P 0. 05 versus control group; # P 0. 05 versus the group with 1 day extinction and saline injection). 250 Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 10 min prior to saline or DCS injection (experiments 2 and 8). PI-3K inhibitor (wortmannin, 5 g/side) (Lin et al. , 2003) or vehicle was administrated to the BLA 10 min prior to saline or DCS injection (experiment 3). Transcription inhibitor actinomycin D (10 g d issolved in 1. 6 l vehicle; 0. 8 l per side) or translation inhibitor (anisomycin, 125 g dissolved in 1. 6 l vehicle; 0. 8 l per side) or vehicle (Lin et al. 2003) was administrated to the BLA 10 min prior to DCS or saline injection (experiment 4) or 25 min prior to fear-potentiated startle test (experiment 6). In the control experiment, PD98059, U0-126, wortmannin, actinomycin D, and anisomycin were injected 25 min prior to the fear-potentiated startle test. Injections were made through 28-gauge injection cannula (model C313I, Plastic-one Products) connected to a Hamilton micro-syringe via polyethylene tubing. Infusion speed was 0. 25 l/ min. The total volume of injection was 0. 8 l per side. Western blot analysis Animals were killed by decapitation 10 min after extinction training. The lateral and basolateral subregions of the amygdala were collected and sonicated brie? y in ice-cold buffer: 50 mM Tris–HCl (pH 7. ), 50 mM NaCl, 10 mM EGTA, 5 mM EDTA, 2 mM sodium pyrophospha te, 4 mM para-nitrophenylphosphate, 1 mM sodium orthovanadate, 1 mM phenylmethylsulfonyl ? uoride (PMSF), 20 ng/ml leupeptin, and 4 ng/ml aprotinin. Following sonication, the soluble extract was obtained after pelleting the crude membrane fraction in a centrifuge at 50,000 g at 4  °C. Protein concentration in the soluble fraction was then measured using a Bradford assay with bovine serum albumin as the standard. Equivalent amounts of protein for each sample were resolved in 10% sodium dodecyl sulfate (SDS)–polyacrylamide gels, blotted electrophoretically to PVDF membranes and blocked overnight in 5% skim milk (Cell Signaling Technology, Inc. , USA).Blots were incubated with antiphospho-ERK antibody (New England Biolabs, USA), anti-ERK antibody (BD Transduction Laboratories, USA), anti-phospho-Akt antibody (New England Biolabs) or anti-pan-Akt (BD Transduction Laboratories). Band detection was performed with an enhanced chemiluminescence Western blotting analysis system (RPN 2108; Amersham International, Amersham, UK). fear-potentiated startle during the pre-extinction test. The ? nal 30 rats were assigned into ? ve groups of six animals based on their level of fear-potentiated startle in the preextinction test. Twenty-four hours after the pre-extinction test, each rat received 1 or 2 consecutive days of extinction training with DCS (15 mg/kg, i. p. ) or saline. Saline or DCS was injected 15 min prior to the extinction training.An additional control group was tested 2 days after the pre-extinction training without intervening exposures to visual CS. Fig. 1B shows that DCS accelerated extinction of conditioned fear. A two way ANOVA for differences in treatment (DCS vs saline) and days (one or two extinction sessions) between-subjects indicated a signi? cant treatment effect (F(1,20) 9. 02) and a signi? cant treatment days interaction (F(2,20) 6. 68). Thus, the reduction of fear-potentiated startle after 1 day of extinction training was greater in the gr oup that received DCS than in the group that received saline (Fig. 1B). Individual comparisons between DCS- and saline-treated groups indicated signi? ant differences after 1 day of extinction sessions (t(10) 3. 86). Previous studies have shown that lesions of the BLA block expression of fear-potentiated startle (Campeau and Davis, 1995). DCS may have toxic effect on BLA, and resulting misinterpretation of its facilitation effects on extinction. To test for toxicity, all animals of experiment 1 were retrained and tested 24 h later. Under these conditions, animals previously injected with DCS or saline showed a signi? cant fear-potentiated startle (Fig. 1C). Thus, the facilitation effect of DCS observed during the post-extinction test 1 appeared to result from the acute drug effect rather than from a more permanent, perhaps toxic, action of DCS.Experiment 2: intra-amygdala infusion of MAPK inhibitors blocked the facilitation of extinction by DCS To test the possible role of MAPK-depe ndent signaling cascade in the DCS-enhanced effect on the extinction of condition fear, 48 rats received fear conditioning, extinction training, and testing for fear-potentiated startle. Initially, 58 rats were used, but 10 of them were excluded. Rats were randomly assigned to six different groups and received one of the following treatments: vehicle saline (VEH SAL), vehicle DCS (VEH DCS), PD98059 DCS (PD DCS), U0-126 DCS (U0 DCS), PD98059 saline (PD SAL) or U0-126 saline (U0 SAL). The MAPK inhibitors, PD98059, and U0-126 (or vehicle) were administrated to the BLA 10 min prior to the injection with DCS or saline. Animals were then returned to their cage.Fifteen minutes after injection, animals were subjected to a single session of extinction training. Previously, we show that a single day of extinction training with cue exposure led to about 35% decrease in fear-potentiated startle, whereas 2–3 days of extinction training led to near complete extinction (Lu et al. , 2001; Wa lker et al. , 2002). We concluded that the acceleration of extinction is best detected after a single session of extinction training. As shown in Fig. 2, DMSO, PD98059 (500 ng/side, bilaterally), or U0-126 (20 nM/per side, bilaterally) was given 10 min prior to saline or DCS injection; rats were returned to their cages for 30 min before a single HistologyRats were overdosed with chloral hydrate and perfused intracardially with 0. 9% saline followed by 10% formalin. The brains were removed and immersed in a 30% sucrose-formalin solution for at least 3 day. Coronal sections (30 M) were cut through the area of interest, stained with Cresyl Violet, and examined under light microscope for cannula placement. Animals with misplaced cannula were not included in later analysis. Statistical analysis The mean startle amplitude across the 30 noise alone and 30 light-noise trials during the pre- and post-extinction tests was calculated for each animal. All results were analyzed using a score of percent fear-potentiated startle, as de? ned in the post-extinction tests above.ANOVA on scores was the primary statistical measure. Between-group comparisons were made using two-tailed t-tests for independent samples. The criterion for signi? cance for all comparisons was P 0. 05. RESULTS Experiment 1: systemic administration of DCS accelerated extinction of conditioned fear This experiment assessed the facilitation effect of DCS on different amounts of extinction training. Initially, 35 rats were used. Five were excluded for showing less than 50% Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 251 Fig. 2. Intra-amygdala infusion of MAPK inhibitors blocked facilitation effect of DCS on extinction. (A) Timeline of behavioral procedures for experiment 2. B) Cannula was placed in the BLA. Percent fear-potentiated startle measured 24 h before (pre-extinction test) and 24 h after extinction training (post-extinction test). Rats in each group underwent VEH SAL, VEH DCS, PD DCS, U0 DCS, PD SAL, or U0 SAL prior to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs (values are mean SEM, * P 0. 05 versus VEH SAL group; # P 0. 05 versus VEH DCS group). (C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). 252 Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 session of extinction training.Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs. Results showed that there was a signi? cant overall difference between treatments (F(5,42) 11. 81). Fig. 2 shows that administration of DCS facilitated extinction of conditioned fear (VEH DCS) compared with the control group (VEH SAL) (t(14) 3. 12, P 0. 05). This effect was blocked by co-administration of MAPK inhibitor PD98059 (PD DCS) or U0-126 (U0 DCS) (t(14) 3. 08, P 0. 05 and t(14) 3. 29, P 0. 05, respectively) compared wit h the control (VEH DCS), treated with PD98059 only (PD SAL) or U0-126 only (U0 SAL) did not affect extinction (t(14) 0. 7 and t(14) 0. 36, respectively). These results indicated that the MAPK dependent signaling cascade most likely mediated the facilitation effect of DCS. Experiment 3: intra-amygdala infusion of the PI-3K inhibitor blocked facilitation of extinction by DCS Previous ? ndings have shown that PI-3K inhibitors retard acquisition in a variety of learning paradigms (Lin et al. , 2003). To evaluate the possible role of PI-3K signaling cascade in the DCS enhancement of extinction of conditioned fear, 32 rats received fear conditioning, extinction training, and testing for fear-potentiated startle. Although 38 rats were used initially, six were excluded.They were then randomly assigned to four different groups and received one of the following treatments: VEH SAL, VEH DCS, wortmannin DCS (WH DCS) and wortmannin saline (WH SAL). The PI-3K inhibitor (wortmannin, 5 g/side, bila terally) was infused to the BLA 10 min prior to the injection of saline or DCS. Then rats were returned to their cages for 15 min before being subjected to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs. Results showed that there was a signi? cant overall difference between treatments (F(4,28) 12. 17). As shown in Fig. 3, the facilitation effect of DCS (VEH DCS) on extinction was blocked by co-administration of PI-3K inhibitor (WH DCS) (t(14) 2. 98, P 0. 05).With the single extinction training session used in this experiment, this dose of wortmannin alone (WH SAL) at this dose had no effect on the extinction of fear-potentiated startle compared with control group (VEH SAL) (t(14) 0. 19). These results suggest that the PI-3K signaling cascade was involved in the DCS facilitation of extinction. Experiment 4: DCS enhanced the extinction training induced MAPK and PI-3K phosphorylation According t o the results of the above experiments, the DCS facilitation effect on extinction was prevented by coadministration of MAPK or PI-3K inhibitor. Previous studies have shown that infusion of these same inhibitors blocks extinction (Lu et al. , 2001; Lin et al. , 2003). Therefore, these treatments in conjunction with DCS must result in no extinction and resulting misinterpretation of its blockage effects on DCS.To show the MAPK and PI-3K signaling pathways are essential for the facilitation effect of DCS, we used Western blot to evaluate the DCS effect on the extinction training induced MAPK and PI-3K phosphorylation. Additional amygdala-cannulated rats received fear conditioning, extinction training, and testing for fear-potentiated startle. Then PD98059 or wortmannin was infused to the BLA 10 min prior to the injection of saline or DCS. Rats were returned to their cages. Fifteen minutes after DCS or saline injection, animals were subjected to a single session of extinction training. Animals were killed by decapitation 10 min after extinction training.The lateral and basolateral sub-regions of the amygdala were tested with Western blot analysis. Compared with control group, MAPK phosphorylation was signi? cantly elevated in BLA after extinction training (Fig. 4A, lane 2). Administration of DCS enhanced the effect of extinction training on MAPK phosphorylation (Fig. 4A, lane 3). The MAPK inhibitor PD98059 blocked the effect of DCS (Fig. 4A, lane 4). In addition, we measured the state of Akt phosphorylation as an index of PI-3K activity (Lin et al. , 2001). Fig. 4B showed that administration of DCS enhanced the effect of extinction training on Akt phosphorylation (Fig. 4B, lane 3). The PI-3K inhibitor, wortmannin, blocked the enhancement effect of DCS (Fig. 4b, lane 4).These results raise the possibility that DCS enhancement effect of extinction of conditioned fear is mediated by the amygdaloid MAPK and PI-3K dependent signaling cascades. Experiment 5: intra-amygd ala infusion of the transcription inhibitor or translation inhibitor blocked DCS facilitation of extinction The MAPK pathway participates in the synthesis of proteins important for the long-term stabilization and storage of fear memories. According to the result of experiment 2, the facilitation effect of DCS on extinction is mediated by the MAPK dependent signaling cascade. We predicted that the facilitation effect of DCS required new protein synthesis in the BLA.To test this hypothesis, 48 rats received fear conditioning, extinction training, and testing for fear-potentiated startle. Initially, 56 rats were used but eight of them were excluded. Rats were then randomly assigned to six different groups and received one of the following treatments: VEH SAL, VEH DCS, actinomycin D DCS (ACT DCS), anisomycin DCS (ANI DCS), actinomycin D saline (ACT SAL), and anisomycin saline (ANI SAL). Transcription inhibitor (actinomycin D, 10 g dissolved in 1. 6 l vehicle; 0. 8 l per side) and transl ation inhibitor (anisomycin, 125 g dissolved in 1. 6 l vehicle; 0. 8 l per side) were administered to the BLA 10 min prior to saline or DCS injection. Then rats were returned to their cages. Fifteen minutes later, nimals were subjected to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs. Results showed that there was a significant overall difference between treatments (F(5,42) 10. 17). As shown in Fig. 5, actinomycin D and anisomycin completely blocked the facilitation effect of DCS (t(14) 3. 11 and t(14) 2. 96, respectively) compared with the VEH DCS group. With a single extinction training session used in this experiment, actinomycin alone (ACT SAL) or anisomycin alone (ANI SAL) did not affect the extinction of fear-potentiated startle compared with control Y. L. Yang and K. T.Lu / Neuroscience 134 (2005) 247–260 253 Fig. 3. Intra-amygdala infusion of the PI-3K inhibitor blocked the fa cilitation effect of DCS on extinction. (A) Timeline of behavioral procedures for experiment 3. (B) Cannula was placed in the BLA. Percent fear-potentiated startle measured 24 h before (pre-extinction test) and 24 h after (post-extinction test) extinction training. Rats in each group were treated with VEH SAL, VEH DCS, WH DCS, or WH SAL prior to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs (values are mean SEM, * P 0. 05 versus VEH SAL group). C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). 254 Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 (VEH SAL) (t(14) 0. 88 and t(14) 0. 48, respectively). These results suggest that new protein synthesis within the BLA played an important role in DCS facilitation of extinction of conditioned fear. Experiment 6: the disruptive effect of intra-amygdala infusion of actinomycin D and anisomy cin was not attributed to lasting damage to the amygdala The active drugs used in the above experiments may have toxic effect within the amygdala. Previous work shows that infusion of PD98095 (Lu et al. , 2001) or wortmannin (Lin et al. 2003) into BLA did not appear to cause permanent impairment of amygdala function. To test for possible toxic effects of actinomycin D and anisomycin on the BLA, all animals of experiment 5 received an additional 2 days of drug free extinction training followed 24 h later by testing. Under these conditions, rats previously treated with actinomycin D (ACT DCS-treated group and ACT SALtreated group) or anisomycin (ANI DCS- and ANI SALtreated group) showed a signi? cant reduction of fearpotentiated startle between post-extinction test 1 and post-extinction test 2 (t(7) 3. 08 and t(7) 3. 32 for the ACT DCS-treated group and ACT SAL-treated group respectively) and (t(7) 2. 96 and t(7) 3. 1 for the ANI DCStreated group and ANI SAL-treated group respectively ) (Fig. 6B). Thus, the blockage of extinction observed during post-extinction test 1 appeared to result from an acute drug effect rather than from a more permanent and perhaps toxic action, of actinomycin D or anisomycin. Previous studies have shown that lesions of the BLA block fear-potentiated startle (Campeau and Davis, 1995), an outcome opposite from that obtained with infusion of actinomycin D or anisomycin. It is also important to note that actinomycin D or anisomycin may have long-term toxicity within the BLA. The extinction of fear would look the same as a gradual loss of ability to express or relearn fear.Experiment 7: the disruptive effect of intra-amygdala infusion of actinomycin D and anisomycin was not attributed to state dependency To evaluate the contribution of state-dependency effects to the results obtained in experiment 6, additional amygdala-cannulated rats were tested for extinction in a drug-free state and after receiving the same compound that they had receive d during extinction training. Results showed that there was a signi? cant overall difference between treatments in post-extinction test 2 (F(2,21) 32. 16). These results are shown in Fig. 7. Rats infused with actinomycin or anisomycin before postextinction test 2 showed a slight, but non-signi? cant, decrease in fear-potentiated startle from post-extinction test 1 to post-extinction test 2. For control rats (n 8), fear-potentiated startle was signi? cantly lower during post-extinction test 2 than post-extinction test 1 (t(7) 2. 455; P 0. 05). The lost of fear-potentiated startle in both groups probably re? cted incidental extinction produced by the 30 non-reinforced CS presentations of post-extinction test 1. The failure of rats infused before Fig. 4. MAPK and PI-3K inhibitors blocked extinction training activation of MAPK and PI-3K. (A) Representative Western blots and densitometric analysis of the activation of MAPK in the BLA under different treatments (values are mean SEM, * P 0 . 05 versus VEH SAL group). (B) Representative Western blots and densitometric analysis Akt phosphorylation as an index of PI-3K activity in the BLA under different treatments (values are mean SEM, * P 0. 05 versus VEH DCS group). Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 255 Fig. 5.Intra-amygdala infusion of the transcription inhibitor or translation inhibitor blocks the facilitation effect of DCS on extinction of conditioned fear. (A) Timeline of behavioral procedures for experiment 5. (B) Cannula was placed in the BLA. Percent fear-potentiated startle measured 24 h before (pre-extinction test) and 24 h after (post-extinction test 1) extinction training. Rats underwent treatment with VEH SAL, VEH DCS, ACT DCS, ANI DCS, ACT SAL, or ANI SAL prior to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs (values are mean SEM, * P 0. 05 comparing with the VEH SAL group; # P 0. 05 compared with the VEH DCS group). C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). 256 Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 Fig. 6. The disruptive effects of intra-amygdala infusion of actinomycin D and anisomycin on extinction were not attributed to lasting damage to the BLA. (A) Timeline of behavioral procedures for experiment 6. The same animals used in experiment 3 were subjected for two more trials of extinction training. (B) Twenty-four hours after the last extinction training, animals were tested for fear-potentiated startle in the absence of drugs (post-extinction test-2) (values are mean SEM, * P 0. 05 versus the corresponding post-extinction test-2). esting with the transcription and translation inhibitors before testing to show a loss of fear-incidental extinction suggested that state dependency was not a major factor in the effects of actinomycin D and anisomycin. Experiment 8: effect of pretest PD98059, U0-126, wortmannin, actinomycin, and anisomycin administration on fear-potentiated startle This experiment was designed to evaluate whether the effect of the active drugs used has had a secondary effect on fear itself or on CS processing. For example, if MAPK inhibitor U0-126 reduced CS-elicited fear, this might attenuate extinction by decreasing the discrepancy between CS predictions and what actually occurred. If actinomycin D or anisomycin interfered with visual processing, this might block extinction produced by non-reinforced exposures to the visual CS.To evaluate these possibilities, 42 amygdala-cannulated rats received acclimation, baseline startle test, and fear conditioning. Initially, 50 rats were used, but eight of them were excluded. After 24 h, rats were infused with PD98059, U0-126, wortmannin, actinomycin, and anisomycin. At 25 min after the infusions, rats were tested for fear-potentiated startle. As shown in Fig. 8, none of the active drugs we used here sig ni? cantly in? uenced fearpotentiated startle (F(6,35) 0. 993). Thus, it is unlikely that these drugs in? uenced extinction by increasing fear or by disrupting CS processing. Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 57 Fig. 7. The disruptive effect of intra-amygdala infusion of actinomycin D and anisomycin were not attributed to state dependency. (A) Timeline of behavioral procedures for experiment 7. (B) Cannula was placed in the BLA. Percent fear-potentiated startle measured 24 h before (pre-extinction test), 24 h after (post-extinction test 1), and 48 h after (post-extinction test 2) extinction training. Rats in each group underwent VEH SAL, ACT DCS, or ANI DCS prior to a single session of extinction training and prior to post-extinction test 2. Animals were tested for fear-potentiated startle in the absence of drugs (values are mean SEM, * P 0. 05). C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). 258 Y. L. Y ang and K. T. Lu / Neuroscience 134 (2005) 247–260 Fig. 8. Effect of pretest PD98059, U0-126, wortmannin, actinomycin, and anisomycin administration on fear-potentiated startle. (A) Timeline of behavioral procedures for experiment 8. (B) Cannula was placed in the BLA. Percent fear-potentiated startle was measured 24 h after fear conditioning. Rats were treated with DMSO, PD98059 (PD), U0-126 (U0), wortmannin (WH), vehicle (VEH), actinomycin (ACT), or anisomycin (ANI) 25 min prior to the fear-potentiated startle test (values are mean SEM). C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). DISCUSSION We build on the previous ? ndings that DCS facilitated extinction of conditioned fear (Walker et al. , 2002; Ledgerwood et al. , 2003, 2004; Ressler et al. , 2004). Here, we show for the ? rst time that the DCS effect was prevented by co-administration of MAPK, PI-3K, transcription, and translation inhibitors. Control experiments indica ted that the blocking effects of actinomycin D and anisomycin on extinction were not due to lasting damage to the BLA or state dependency. In addition, none of active drugs we used in this study altered the expression of conditioned fear.These results suggest that PI-3K and MAPK-dependent signaling cascades and de novo protein synthesis within the BLA were important for DCS facilitation. Early behavioral studies by Pavlov (1927) and Konorski (1948) de? ned extinction as an active process involving formation of new inhibitory associations as opposed to forgetting previously conditioned associations. Numerous studies since have con? rmed and elaborated these early ? ndings (reviewed in Falls and Davis, 1995; Davis et al. , 2000). It is now well accepted that extinction occurs with repeated presentation of a CS in the absence of the pre- Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 259 viously paired US.This reduces the conditioned response elicited by the CS. In co ntrast to forgetting which implies the passive loss of memory, extinction implies active formation of new inhibitory associations competing with and overpowering original excitatory associations. Evidence is growing that extinction may involve circuits and use mechanisms of synaptic plasticity similar to those of conditioned fear learning (Falls and Davis, 1992; Cox and Westbrook, 1994; Baker and Azorlosa, 1996; Davis et al. , 2000). NMDA-dependent synaptic plasticity appears to mediate many forms of active learning (Morris, 1989; Staubli et al. , 1989; Flood et al. , 1990; Collinridge and Bliss, 1995).It is likely that conditioned fear learning depends on CS–US pairing mediated by NMDA receptors within the BLA (Miserendino et al. , 1990; Fanselow and LeDoux, 1999). Extinction also appears to require active, NMDA-dependent learning within the amygdala. This was demonstrated by blockage of extinction by microinjections of APV into the BLA in both fear-potentiated startle (Fall s and Davis, 1992) and freezing paradigms (Lee and Kim, 1998). Furthermore, systemic administration of a different NMDA antagonist, MK801, blocks the extinction process in a range of different learning paradigms (Cox and Westbrook, 1994; Baker and Azorlosa, 1996; Kehoe et al. , 1996).Recently, DCS, a partial agonist acting at the strychnine-insensitive glycine-recognition site of the NMDA receptor complex, has repeatedly been shown to facilitate learning in various cue and context association paradigms (Monahan et al. , 1989; Flood et al. , 1992; Thompson and Disterhoft, 1997). Walker et al. (2002) reported the ? rst evidence that DCS facilitates extinction of learned fear. Since then, further studies con? rmed and elaborated this early ? nding (Ledgerwood et al. , 2003, 2004; Ressler et al. , 2004). These studies reported that DCS is more effective at facilitating extinction when given after extinction training, rather than before. They interpret these ? dings as evidence that DCS facilitates the consolidation of a new memory acquired during extinction. It is important to note that although some studies have shown DCS to be effective in improving memory impairment due to Alzheimer’s disease (Schwartz et al. , 1996; Tsai et al. , 1999) and schizophrenia (Javitt et al. , 1994; Goff et al. , 1999), other studies found little or no improvement (Tsai et al. , 1998; van Berckel et al. , 1999). This may be related to the fact that acute treatment with DCS may have a more pronounced facilitation than chronic treatment (Quartermain et al. , 1994; Ledgerwood et al. , 2003; Richardson et al. , 2004). Ledgerwood et al. (2003, 2004) reported that DCStreated animals fail to exhibit reinstatement effects.That DCS enhances extinction may be through some processes different from extinction induced by repeat representation of CS. Lin et al. (2003) investigated the similarities and differences between consolidation of conditioning and consolidation of extinction. They fo und that both processes depend on activation of NMDA receptors, PI-3K, MAPK, and require synthesis of new proteins within the amygdala. They also found that different characteristics show differential sensitivity to the transcription inhibitor actinomycin D. Our results were consistent with the model that the extinc- tion process involved active learning of new inhibitory associations.Here we showed that DCS facilitation of extinction could be blocked by actinomycin D and anisomycin. These seemingly con? icting results could be attributable to our extinction protocol. Our protocol resembled betweensession extinction, presumably corresponding to long-term extinction memory. In addition, we used DCS to facilitate the extinction process and tested the animals in a drug free condition. Acquisition or consolidation of long-term memory requires activation of protein kinase, transcription of genes, new protein synthesis, and synapse formation (Schafe and LeDoux, 2000). Similar mechanisms w ere involved in the DCS facilitation of extinction. The DCS activated NMDA receptors, resulted in Ca2 in? x into the cell, and led to the PI-3K and MAPK activation. Activated MAPK can translocate to the nucleus, subsequently activating transcription factors to promote gene transcription and new protein synthesis. Thus, combinations of drugs and extinction training may weaken or erase original memory. There is increasing evidence that learning of CS–US associations involves synaptic plasticity within the BLA, leading to differential activation of this circuit by sensory afferents (Davis, 1997; Rogan et al. , 1997; Lee and Kim, 1998; Fanselow and LeDoux, 1999). Our results suggested that the extinction of conditioned fear also involved NMDA-dependent plasticity, but speci? inhibitory circuits may be activated by extinction learning. We hypothesize that this newly activated inhibitory circuit would oppose conditioned excitatory pathways normally leading to activation of the cent ral nucleus of the amygdala, resulting in the elicitation of fear responses. CONCLUSION This may be the ? rst study to show that PI-3K and MAPKdependent signaling cascade and de novo protein synthesis within the BLA were essential to the DCS facilitation of the extinction of conditioned fear. Acknowledgments—The work was supported by grants from the National Science Council (NSC 90-2320-B-003-007, NSC 902320-B-006-038, NSC 93-2320-B-003-003).Our gratitude (also) goes to the Academic Paper Editing Clinic, NTNU. REFERENCES Baker J, Azorlosa J (1996) The NMDA antagonist MK-801 blocks the extinction of Pavlovian fear conditioning. Behav Neurosci 110:618–620. 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Asch Study Research Paper

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Women's Clubs as Vehicles for Reform - Assignment Example Betty Chapman an author, a historian, teacher and librarian, clearly shouts out the above mentioned issues in her easy women’s clubs as vehicles for reforms in Houston (Chapman 1885-1918). Women clubs in Houston have done a great deal in turning things around in Houston no matter the race or religion background. She stipulates how laws in Texas had prevented married women from the use of public property earnings in running their businesses. They were not allowed to sign contracts in their own name. Therefore, the Houston women’s clubs were obligated to fight for their rights and be allowed to earn from public property and conduct their businesses. These women’s grievances led to the Houston law reforms to allow women to have access to own their own businesses despite from being married (Chapman 1885-1918). Women’s clubs have led to tremendous reforms in Houston as Betty Chapman depicts and thus she calls them as vehicles for reforms because they have revolutionized how things are done. They have advocated for leadership as well as alimony payments to mention just a few. In conclusion, I do agree with Betty Chapman’s opinion of women’s clubs as vehicles for reforms because of the commitment they have to promote women in development. Without a doubt, women clubs should be advocated in all major states to help fight for the marginalized women and pave a better life for

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International business - Movie Review Example Among those victims is a senior risk-management executive, who was working on a major analysis just when he was let go. As the person is leaving he hands a USB drive to an analyst who works late in the night. The data on the usb disturbs him and turns out to be first rumbling of the storm. He unlocks information that could prove to be the downfall of the firm and further finds out that both the market and the company are about to crash. On this he calls his seniors and colleagues in and informs them about the companys financial disaster which follows an emergency meeting and a long panicked night until dawn when the owner of the company John Tuld arrives. The owner is informed of the financial crisis which the company was facing over the past 40 months the company have packaged a series Mortgage Backed Securities (Mbs) into one tradable commodity. The idea was quite profitable but it requires a month to layer the products that is, they have to hold the products for a longer time than desired and they are based on mortgages and risk is elevated. The company’s (MBS) have decreased by 25%, and that was the rate at which the losses will exceed even the current value of the company. The company based on historic patterns, had exceeded their levels of volatility that is their historic volatility has exceeded the limits. They were already facing the crisis as the company has broken through for the past 5 days. The owner was told it will take weeks to clear the problem and if they stop buying it will be noticed and they were left with 60 traders only. The owner inquires how bad the situation was and he was told that the company was al ready in a crisis, the young analyst also informs him that him if the assets were to be decrease by just 25%, it will exceed the value of the company. The decision made by the owner was to

Leveraging Data, Information, and Knowledge for Competitive Advantage Essay

Leveraging Data, Information, and Knowledge for Competitive Advantage - Essay Example The solution then came out to be the term which is now known as competitive advantage. The term means that internal factor or product strength or critical success factor or the product itself or any service which one specific organization does best when it comes to the others in the same industry. (Hope, 1997) When that edge is maintained over time, not permanently, but for a significant amount of time, and when a noticeable amount of market share is snatched by that particular company, based on that factor that only this company possesses over its competitors, then that is known as the competitive advantage that one firm has in the industry that it belongs to. Companies are always striving to efficiently and effectively utilize the resources that they have and gain a competitive advantage over the rivals that they have, since having one goes a long way in making the company successful and stand out in the market, increasing the goodwill both in the eyes of customers and all other st akeholders associated with the company. As mentioned above, such a competitive advantage is not permanent, thus a company should not release the pressure of competition once a competitive advantage has been gained. Rather, they should continually try to develop themselves to achieve the zenith when it comes to different factors, so that an edge can be maintained over time and with consistency. Management Information Systems (MIS) are not the regular computer systems, since they specialize in providing the user with analysis of all the other information systems that are synchronized with it and which take care of all the operational activities which take place in the organizations. Usually the daily decision making that a manager has to go through is more or less related with the those activities which have a direct effect on the cash flows and liquidity of the company, that is, the operational activities. (Davenport, 2000) And therefore, the MIS systems make use of

Environmental Laws and Regulations Essay Example | Topics and Well Written Essays - 500 words

Environmental Laws and Regulations - Essay Example nt environmental laws under the UN Conferences on Climate Change (Montreal and Kyoto Protocols), there is strident opposition from the powerful industry lobbies, especially in the developed world, to such efforts. Their arguments are mainly based on the reliability of the predictions of the impending drastic global warming on the one hand, the exorbitant costs of meeting the new emission norms, and the impact of such costs on industry competitiveness and profitability. Competitiveness and profitability are at best comparative measures in a given set of circumstances. It has been proven time and again that compliance to laws is more economical than paying the penalties for an environmental disaster. ‘Polluter pays’ is now an accepted principle. If environmental laws are not fully implemented or are violated, the potential risk of unforeseen liability also has to be counted in the profitability calculations, and this was not being All calculations of competitiveness and profitability are reduced to nothing, and the very survival of a business is threatened, when it has to pay millions or billions of dollars as penalty for non-compliance. The Bhopal Gas Tragedy (dubbed as ‘Hiroshima of the Chemical Industry’), which killed more than 2000 and injured over 300,000 people, cost Union Carbide $500 millions (Pratima, 1998). This is a pittance since it occurred in India and would have run into several billions if it occurred in the USA. Exxon Valdez oil spill was of catastrophic proportions on marine life, with hundreds of thousands of birds killed, fish poisoned, and large-scale death of other marine life like seals, sea otters and whales. Exxon spent $ 2.2 billion in clean up operations, while the total cost was of the order of $ 4 billion (Thinkquest). The adverse publicity of such events through the print and electronic media can threaten the very survival of the concerned businesses. At individual level, consumers are concerned with the quality of their

Genetic Engineering Philosophical Paper Essay Example for Free

Genetic Engineering Philosophical Paper Essay Genetic Engineering Defined We live in a period of science breakthroughs and accomplishments.   For over centuries now, science has been constantly pursuing its ambition to hold nature’s natural course within its grasp.   Perhaps one field that can fit this description is genetic engineering which is a laboratory technique to change the DNA of living organisms (What is Genetic Engineering).   A good view of genetic engineering can perhaps be seen in the film Gattaca where one of the main characters, Vincent (played by Ethan Hawke), is not able to accept his genetic fate.    Basing on his character, the film views how genetic engineering can affect an individual’s self-esteem as well as how far it can push him to practice free will to fill this sense of emptiness. Effects of Genetic Engineering As to its effect on society, the movie shows how it serves as a solution in eliminating if not minimizing the consequences of genetic imperfection such as in-born diseases.   In fact, some also believe that genetic engineering can be beneficial not only with health and medicine but as well as food, agriculture, manufacturing, etc.   Even nowadays genetics have already made its benefits known by aiding in forensic investigations through DNA identification thus lessening the number of violent crimes (Genetic Engineering Benefits Society). However, there can also be possible risks when relying on this field of science particularly with eugenics, or the selection the future makeup of children which could lead to the elimination of some personal traits.   Another risk would be in the usage of biotechnology before exploring other options in terms of reproduction.   One example is implanting an egg from one woman into the uterus of another which might be hazardous if considered as a primary technique (Discovery Education: Genetic Engineering) Perhaps one of the things that the director of the movie Gattaca is trying to present is how genetic engineering can be a remedy or solution in altering human fate by making him somewhat more invincible.   After watching the film, I saw this field of science as something that can affect a person’s religious faith. This issue has been reinforced furthermore by the scene particularly during the birth of Vincent where he said, â€Å"He never understood what possessed his mother to put her faith in God’s hands rather than those of her local geneticists.† secondary to his rejection of the fact that he is too genetically imperfect to achieve his dreams.   As far as the film is concerned, this showed how genetic engineering can have the potential to tolerate such human behaviors which can ultimately lead him to play God once he gets the chance instead of practicing self-acceptance and humility. Ethical Implications of Genetic Engineering It has an ethical implication especially when it comes to religion.   Taking the views of the Church of Scotland for example, it states that although Christians have long regarded scientific research as a way of responding to God’s commands of â€Å"filling the earth and subduing it† from the first chapter of Genesis in the bible, it is but important to draw a line especially in the level of genetics as it is an alteration and manipulation of human genetics which is God’s exclusive rights only. Perhaps there would be exceptions such as issues that call for certain necessities like modifying pig hearts and lungs in case of serious shortage of suitable human donor organs.   However with or without the religious point of view, some practices of genetic manipulation can endanger the life of certain people if these are not properly controlled or monitored especially since we do not hold enough knowledge in harmfully interfering with nature.   Furthermore, this also distorts virtues like humility and creates erroneous perception of what people should be made up of physically in order to be happy (Are We Playing God?). The Swimming Scene   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   This particular scene in the movie gives a certain twist in the view of genetic engineering.   Vincent was born with a 99% probability of heart disorder and so every time they do the swim race when they were kids, he often got tired first and lost to Anton.   But when they did it again when they were already grown ups, Anton lost the race and almost drowned.   When Vincent defeated Anton in the swimming race for the first time, this ultimately showed the strength of human spirit and how it can defeat even the genetically superior.   Apparently, it was as though Vincent was able to unconsciously imbibe self-confidence after all those times he spent with the genetically-engineered individuals. Uma Thurman’s Character   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Irene, Vincent’s love interest whom he met in Gattaca, is another perfect example of an individual who lacks self-confidence and spirit.   Compared to Vincent, her genes are almost perfect if not for a certain heart condition.   Perhaps it is due to the fact that Irene has also been a subject of comparison in Gattaca along with the pressures of being considered for a mission to Titan (one of the moons of the planet Saturn) that she is made to focus on her imperfection although in fact it is â€Å"smaller† as compared with her superior qualities.   If she were living in a community much normal than Gattaca, then there might be a greater chance for her to be happy and see her beautiful qualities.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   With regards to Irene’s character, I think what the director is trying to show is that not even technology can answer for a person’s search for self-fulfillment.   Technology is also capable of deceiving people from seeing reality or from seeing what a person truly is.   Irene fell in love with Vincent in the film but little did she know that he is no more than a mere trespasser in the space agency if not for the help of his friend Jerome, a genetically superior individual who was paralyzed by a car accident and gave his identity to Vincent. The Ending   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   The movie had an amazing ending.   After all the struggles and suspense, Vincent was surprisingly able to pull everything off and made it to the space mission, defeating the majority of his genetically-superior colleagues in Gattaca and taking Jerome’s identity with him.   Jerome on the other hand, committed suicide.   Jerome’s tragic end is the saddest part of the movie.   He has been completely consumed by his misfortune that he literally gave his life away.   He just could not accept what has become of him and the identity that he lost from the accident was the only person he knew how to be, a winner.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   As to Jerome’s suicide, this brought up an ethical issue that perhaps society cannot approve.   Once again it goes against the views of religion about God’s prerogatives of the human life.   Jerome willing his own death cannot be considered a rightful one for even though he had broken a spine or is out of money, his brain was still functioning well, he was speaking very well, and most of all he did not even lose his good looks from the accident so there could have been a chance for him to charm his way to love. According to an article about ethical issues related to life and death, a person only can have a self-imposed death if he has a terminal illness and his physician proclaims certain death in the very near future wherein artificial bodily support is deemed useless considering the very short period of time left (Ethical Issues Related To Life And Death).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   The final scene was both puzzling and funny.   There was the main character about to board the space mission and after successfully making it through several nerve-wracking genetic testing, his urine test finally revealed his true invalid identity.   Yet for some strange reasons, the one in charge of this final step let him through after a brief sentimental conversation about his son being a big fan of Jerome a.k.a. Vincent. I cannot figure out whether to consider human compassion as a part of this scene.   But more importantly, what made the ending very significant is the overwhelming sense of triumph that the main character has brought with him after making to the mission and the great sense of relief that he was not apprehended despite revealing his true identity.   The ending of the story gives out a message that no matter how much we go through or change ourselves, we can never lose the person that we truly are and even the best technology cannot take that away. Reference    What is Genetic Engineering. Mothers for Natural Law.   Retrieved 11 February 2008 at http://www.safe-food.org/-issue/ge.html Are We Playing God? Moral and Ethical Issues in Gene Therapy.   Retrieved 11 February 2008 at http://www.srtp.org.uk/genthpy1.htm#Manip Coates, J., Mahaffie, J., and Hines, A.   2007.   Genetic Engineering Benefits Society.   Retrieved 11 February 2008 at http://encarta.msn.com/sidebar_461576345/Does_Genetic_Engineering_Benefit_Society_.html Genetic Engineering.   Discovery Education.   Retrieved 11 February 2008 at http://school.discoveryeducation.com/lessonplans/programs/geneticengineering/ Ethical Issues Related To Life And Death.   Retrieved 11 February 2008 at http://www.anabaptists.org/tracts/deathtrc.html

Cebu My Hometown Essay Example for Free

Cebu My Hometown Essay Cebu is located in central visayas approximately 1 hour from manila via airplane, Cebu is known for delicious roasted pork and famous in the works of guitars and delicious pastries. Cebu is one of the famous cities around the country as Famous Places in Philippines by ShareRanks three years ago. I will tell you the beautiful sights and relaxing places located in Cebu but not all. First is the Trans-central Highway a 33 kilometer long road from barangay Lahug Cebu city to Balamban(my home town). Some views in Trans-central are breath taking, and it is a 930 ft. above sea level highway. Island in the Sky is one of the best place to visit in Trans-central Highway, they have a small swimming pool and a short hanging bridge, and cottages that you can hang out and eat with your family and friends. Adventure Cafe also located in Trans-central Highway, walking distance from Island in the Sky, and good thing about Adventure Cafe is their adventure base activities such as zip line, wall climbing, rappelling, and stress walk, but honestly haven’t tried their activies, maybe when I go back. There are more place to visit in Trans-central Highway, buy i can only mention two places you can visit. And the last place I want to share is the Whale shark watching, it’s not in Trans-central Highway, there is no whales in 930 ft. above sea level. (haha) It is located in Tan-awan, Oslob, Cebu, 2-3 hours travel or around 177 kilometers south from the Cebu City. There are beaches that offers a tour and rentals for motor banka, but it is very expensive for non-Oslob residents. Whale shark watching is not only available in south side Cebu, but also in north side Cebu. So today I told you the beauty that you can find in my home town, But that’s not all, there are plenty of places you can discover by yourself.

The Laugher Of The Medusa | Analysis

The Laugher Of The Medusa | Analysis Throughout history, women have been excluded from any kind of writing that could allow them the participation in the making of history and culture. Being considered as creatures of lesser rank in mental capacities and intellect, women have been, over centuries, kept in the dark by a patriarchal system that has successfully muted their needs for expression, be it physical, oral or written. In her fundamental essay The Laugh of the Medusa, Hà ©là ¨ne Cixous, French philosopher and feminist critic, openly introduces this idea of womans need for writing as a biological drive which intimately relies on her ceasing back and mastering her own body that has been violently miused by males rhetoric , as Toril Moi asserts that always and everywhere, the rational, active, masculine intellect operates on the passive, objectified, feminized body (189). Its only from the bodily experience that women, according to Cixous, can give birth to an  «Ãƒ ©criture fà ©minine  » which will subvert the phallocentric discourse of masculine writing, along with the logocentric representational system through which it functions. The purpose of this paper is to examine the key insights that the author explores in her essay, mainly the feminine writing  [1]  with the idea of sexual differences. It is, also, necessary to consider, in the following stages, how Cixous makes use of Freuds and Lacans psychoanalysis and Derridas deconstructist theory to disrupt the phallocentric assumptions, hence to break up with all forms of repression against women. A particular focus will be on the critics contribution to French feminism and Anglo-American feminist theory. Le Rire de la Mà ©duse was written by Cixous in 1975, and translated into English as The Laugh of the Medusa in 1976 by Keith Cohen and Paula Cohen. This influential essay, essentially adressing women in order to  « bring them to writing  » (Cixous 875), is expressed in a beautiful and poetic language to convey the idea of the existence of an à ©criture fà ©minine, which is already used by the author. As with many of her writings  [2]  , Cixouss The Laugh of the Medusa revises sexual differences between men and women from past to present, anticipating a future radical change in the perception of this notion which would only take shape if woman takes back a body that is hers, from the masculine repressing language, in order to employ it as a cause and effect of a new genre of writing which Cixous introduces as the feminine writing. The whole premise of the essay is that  « Woman must write her self: must write about women and bring women to writing .  » (Cixous 875). In the light of this idea, the critic goes on to relate womens writing to their bodily experiences that represent a source of desire and urge for creativity. In other words, for a woman to be able to break up with the old traditional doormat in her skin, she must trace her own body with a feminine language. As a result, women will create their own tradition of writing, embarking from the past and its repressive language. Over centuries, masculine discourse has been the dominant and the stronger one. Women had no word to say in a patriarchal universe where, as Cixous states, they were regarded as  « dark  » and  « dangerous  » (878). Women have, accordingly, developed a sense of resentment for other women and themselves under the influence of the masculine ideology. To break up with this complex, Cixous calls woman to manifest through a writing that belongs to her ; but which can neither be defined nor theorized (883) since, as it can be deduced, language is males property, and there is no room to theorize a feminine writing within the masculine dominant discourse. However, the feminine mode of writing can be described as revolutionary against the phallocentric language and thought (888). Cixouss point is to approach this genre of writing in relation to sexual differences and gender in order to demonstrate how these differences have served historico-cultural purposes to hinder womens intellect ual capacities. She goes further to discuss the traditional idea of bisexuality as neutrality- that engenders the fear of lacking  [3]  , contrasted with a bisexuality, that allows one to identify one self as having sexual orientation toward the two sexes. From this equation, Cixous concludes that  « woman is bisexual  » by the nature of her organs and the turning shifts of events; whereas man cannot be so without losing his phallocentric masculine identity (884). In the same way, she believes that writing is bisexual, for women should write to women and men without no exclusion. Throughout the article, Cixous sensibilizes women to the urgent need of a universal revolution against the phallocentric discourse to which they have been the signified subject. By creating their a discourse of their own, women will fly through and, at the same time, steal back that which is already theirs  [4]  , their voices that have been repressed. The author points out to the fact that this subjugation has resulted in creating a female voice consciousness which, aware of the difficulties that women have undergone, reclaims their socio-cultural identity and their natural rights. She also argues for womens freedom to have children or not to have any, without being  « threatened  » or blamed for the choices they make in life (890). The main purpose of this study is to analyze the key insights that Cixous discusses in The Laugh of the Medusa, along with the major influences that affect her writing, namely the Derridian deconstruction and psychoanalytical theory. As its title indicates, the essay includes the  « Medusa  » as a metaphor to portray womans beauty, oppression and intelligence at the same time. By using this Greek mythical figure  [5]  , Cixous hits two birds with one stone : she firstly alludes to women being treated badly by their male counterparts, as Medusa was once ill-treated and raped. On the other hand, the author also hints to womens jealousy of and hatred to other women under the influence of the masculine worldview. Cixous goes on to develop this idea when she argues that men  « have committed the greatest crime against women. Insidiously, violently, they have led them to hate women, to be their own enemies  ». In the same way, the Medusas metaphor is associated with the modern psychoanalytic interpretations of Sigmund Freud who refers to the Medusas head as  « the supreme talisman who provides the image of castration associated in the childs mind with the discovery of maternal sexuality and its denial  » (Freud). Cixous takes on the idea of castration, by which the phallocentric mind is haunted, and relates it to the Medusas image so as to prove that man is unconsciously weak at the sight of the feminine sex, to the point that he is  « consumed, as Freud and his followers note, by a fear of being a woman  » (884). At this level, the critic implicitly alludes to the French psychoanalytist Jacques Lacan, who follows Freud in his concept of Wunsch  [6]  to arrive at a  « desire  » that is associated with a lack. According to Lacans theory of Lack, as explained by Joel Dor in his Introduction to the Re ading of Lacan, womans desire towards the masculine body does not originate from the body itself as the object of desire ; rather, it originates from her lacking a penis ( Dor 236). Ironically, Cixous refutes this  « phallocratic  » analysis arguing that her personal desire of the other is for the other, and that  « a desire originating from a lack  » is much poor and lacking(891). She goes further to criticize women who madly fetishize the masculine sex, treating them of  « the woman of yesterday  » who is either kept in the dark ages, idolizing the traditional way the big penis takes her ; or falsely modernized with naive virtuous thinking as Cixous affirms here :  « They still exist, easy and numerous victims of the oldest of farces: either theyre cast in the original silent version in which, as titanesses lying under the mountains they make with their quivering, they never see erected that theoretic monument to the golden phallus looming, in the old manner, over their bodies. Or, coming today out of their infans period and into the second, enlightened version of their virtuous de-basement, they see themselves suddenly assaulted by the builders of the analytic empire and, as soon as theyve begun to formulate the new desire, naked, nameless, so happy at making an appearance, theyre taken in their bath by the new old men, and then, whoops! Luring them with flashy signifiers, the demon of interpretation  » (892) Following this idea, Cixous is harshly attacking the masculine phallocentric values in the personae of Freud and Lacan, whom she accuses of exploiting the new version of  « modern  » woman to satisfy their sexual needs while theyre reducing them to an inferior and negative position. One cannot understand Cixouss ideas without going back to the Freudian and Lacanian psychoanalytic theories. If we examine Freuds interpretation of sexual differences which place man in a superior position for biological reasons  [7]  , it would then be obvious why he has been criticized by feminists  [8]  , including Cixous. Though she mainly builds her theoretical legacy on psychoanalysis, precisely Freuds, Cixous uses this latters analysis of developmental theory and gender roles -which are based on the biological differences between man and woman- as a counter-argument to assert that, though there is a sexual difference, women should be treated equally, and not in terms of the Lacanian binary oppositions, as she states :  « writing has been run by a libidinal and cultural-hence political, typically masculine-economy; that this is a locus where the repression of women has been perpetuated, over and over, more or less consciously, and in a manner thats frightening since its often hidden or adorned with the mystifying charms of fiction; that this locus has grossly exaggerated all the signs of sexual opposition (and not sexual difference), where woman has never her turn to speak  ». (879) In the same way, Cixous criticizes Lacans theory of phallocentrism which posits the phallus in the centre of the masculine being. Furthermore, the critic employs this primacy of the phallus in the Derridian deconstructist critique of logocentrism to coin the term  « phallogocentrism  », which refers to a (superior) masculine language centered upon the phallus, opposed to a (deficient) feminine language which lacks a phallus. In other words, her writing is a deconstructist one through which she undermines the phallocentric ideology that dominates language (Tidd 98). In addition to the medusas image which is used by the author to overcome Freuds  « castration  » and Lacans  « lack  », is the metaphor of Dora  [9]  that strongly disturbs Freuds legacy in psychoanalysis and therapy. When she directly adresses Dora as  « the true mistress of the Signifier  » (886), Cixous evokes the story of humiliated girl who was manipulated by her father as a pawn in a sexual game between him and his mistresss husband, and later by Freuds therapy that tried to convince her of the necessity to play the game. As a result, the girl was a subject of a double oppression, applied firstly by the father, and secondly by Freud. The case of Dora in the essay, if it alludes to patriarchal ideology and oppression of the females voice, it does not fail to deconstruct the Freudian assumptions of male superiority and the Lacanian theory of  « the Name of the Father  » which prescribes the father as a symbol of law and order. For Cixous, the name of Dora repr esents more than an example of the psychological violence caused by males oppression; she rather employs it as an icon of females revolution and manifest (Showalter 332). The Laugh of the Medusa is the most significant example of Cixouss  « à ©criture feminine  ». Rich of artistic metaphors and innovative ideas, this influential essay is inscribed as a fundamental work of art within literary and critical theory. Influenced by the deconstructist and differentialist thought, Cixouss writing has been effective in undermining the patriarchal dominance over language. By revising the question of sexual differences existing in the psychoanalytical theories of Freud and Lacan, she deconstructs the equation of the binary oppositions applied to the couple man-woman, while intelligently adopting the difference to prove the equality rather than the opposition between the sexes. The idea is recognized through feminist critiques like Shiachs  « Their Symbolic Exists- it Holds Power  » in which she notes :  « Cixous has represented the process of differentiation in more social terms, and has offered the possibility of more hopeful conclusions: the construction of new sorts of identity, which cut across dual hierarchized oppositions  ».( 165) Her poetic language and feminine style is a demonstration of what she calls  « à ©criture fà ©minine  ». Influenced by her reading of James Joyce and Virginia Woolf, Cixous seems to take up their experimentation and modernist mode of writing, herded with a feminine sensual voice and experience, as essential features of a new form, which is the feminine writing. Consequently, introducing this idea, among many others, into the critical theory has undoubtedly made of Cixous one of the most prominent figures of French feminism. When translated into English, Cixouss The Laugh has gained international interest, mainly by Anglo-American feminists. Admittedly, the author has been often criticized  [10]  for considering the sexual differences and making them as a basis for her argument, which, for certain critiques, cannot but reinforce the unequality, hence, repression. To make sense of her ideas, however, one has to contextualize them within a poststructuralist framework. Being a deconstructist par-excellence, Cixous emphasizes the differences in order to deconstruct them. For a deep understanding of her writing, it is crucial to be familiar with psychoanalytical concepts of Freud and his readers, so as to make sense of them in a Cixousian shape. Karen L. Taylor recognizes Cixouss legacy, against Morag Shiachs critique  [11]  , when she states : Furthermore, through her writing, Cixous engages in a psychoanalytical exploration of the feminine. Reading and writing are, for her, the means to grapple with the enigma of male / female relations. She has been criticized for her psychoanalytical style, influenced by Jacques Lacan, and marked by a superabundance of images. Nonetheless, Cixous has been instrumental in establishing a new form of literature that lies somewhere between myth and novel.  » ( 70) What Cixous does is more than claiming equal civil rights for women with regards to their male counterpart. What she does is deconstructing the patriarchal language that hierachizes woman into inferior positions, calling at the meanwhile for a new mode of writing that inscribes the feminine as equal to the masculine, hence, anticipating a possibility of change in social structures. Through the  « à ©criture fà ©minine  », the feminine body  « will produce far more radical effects of political and social changes than some might like to think  » ( Cixous 882).

Fresh Water Turtles :: science

Fresh Water Turtles Fresh Water turtles are small, yet amazing creatures to have and care for in your home. River Cooters, Red Eared Sliders, and Painted turtles are all common pet’s found in America. Though turtles are fun to have around they do require special care just like any other pet would. In most cases they make great pets but turtles aren’t the easiest pets to have so depending on your lifestyle you should think about how much time you’re willing to put into a turtle. They are usually cheap to buy yet the equipment for your turtle can get expensive. Along with cost you must find the time to put into this pet. They need nice set ups to live in as well as attention and proper handling. A turtle’s habitat is vital for their health. Depending on the size and type of turtle you need to make sure you have an adequate home for it. If you decide to keep the turtle inside you need a large aquarium, no smaller than 20 gallons and if you have a baby turtle this will allow a little more room for growth so it will last you a bit longer than a smaller aquarium would. Filters are needed for this aquarium so you do not have to clean it out every day. A clean aquarium is very important for the turtle’s health. Water turtles like to bask out of the water in the sun or under an Ultraviolet (UV) light, which provides the same effect as the sun would, so for this you need a place they can climb out and bask. This is also so they can rest from swimming in the water. These basking rocks, or even floating cork for younger turtles, are very important, they have to have a place to bask and get out of the water. Yet if you decide to keep it outside be sure to provide a place to bask, plenty of water, filters, and a covering so other predators can not harm or eat your turtle. Equipment will be different for indoors or outdoors. If you keep your turtle indoors be sure that it can occasionally get fresh air and sun light, but do not keep an aquarium next to a window! Also, make sure your aquarium or pond is clean, this is extremely important to maintain good health for the turtle and provides them with a clean habitat.