Rigoberta Menchu Rebel of Guatemala

Rigoberta Menchu Tum is a Guatemalan activist for native rights and winner of the 1992 Nobel Peace Prize. She rose to fame in 1982 when she was the subject of a ghost-written autobiography, I, Rigoberta Menchu. At the time, she was an activist living in France because Guatemala was very dangerous for outspoken critics of the government. The book propelled her to international fame in spite of later allegations that much of it was exaggerated, inaccurate or even fabricated. She has kept a high profile, continuing to work for native rights around the globe. Early Life in Rural Guatemala Menchu was born Jan. 9, 1959, in Chimel, a small town in the north-central Guatemalan province of Quiche. The region is home to the Quiche people, who have lived there since before the Spanish conquest and still maintain their culture and language. At the time, rural peasants like the Menchu family were at the mercy of ruthless landowners. Many Quiche families were forced to migrate to the coast for several months every year to cut sugarcane for extra money. Menchu Joins the Rebels Because the Menchu family was active in the land reform movement and grass-roots activities, the government suspected them of being subversives. At the time, suspicion and fear were rampant. The civil war, which had simmered since the 1950s, was in full swing in the late 1970s and early 1980s, and atrocities such as the razing of entire villages were commonplace. After her father was arrested and tortured, most of the family, including 20-year-old Menchu, joined the rebels, the CUC, or Committee of the Peasant Union. War Decimates Family   The civil war would decimate her family. Her brother was captured and killed, Menchu said she was forced to watch as he was burned alive in a village square. Her father was a leader of a small band of rebels who captured the Spanish Embassy in protest of government policies. Security forces were sent in, and most of the rebels, including Menchus father, were killed. Her mother was likewise arrested, raped and killed. By 1981 Menchu was a marked woman. She fled Guatemala for Mexico, and from there to France. I, Rigoberta Menchu It was in France in 1982 that Menchu met Elizabeth Burgos-Debray, a Venezuelan-French anthropologist, and activist. Burgos-Debray persuaded Menchu to tell her compelling story and made a series of taped interviews. These interviews became the basis for I, Rigoberta Menchu, which alternates pastoral scenes of Quiche culture with harrowing accounts of war and death in modern Guatemala. The book was immediately translated into several languages and was a huge success, with people around the world transfixed and moved by Menchus story. Rise to International Fame Menchu used her newfound fame to good effect -- she became an international figure in the field of native rights and organized protests, conferences, and speeches around the world. It was this work as much as the book that earned her the 1992 Nobel Peace Prize, and it is no accident that the prize was awarded on the 500th anniversary of Columbus’ famous voyage. David Stolls Book Brings Controversy In 1999, anthropologist David Stoll published Rigoberta Menchu and the Story of All Poor Guatemalans, in which he pokes several holes in Menchu’s autobiography. For example, he reported extensive interviews in which local townsfolk said that the emotional scene in which Menchu was forced to watch her brother burned to death was inaccurate on two key points. First of all, Stoll wrote, Menchu was elsewhere and could not have been a witness, and second, he said, no rebels were ever burned to death in that particular town. It is not disputed, however, that her brother was executed for being a suspected rebel. Fallout The reactions to Stoll’s book were immediate and intense. Figures on the left accused him of doing a right-wing hatchet job on Menchu, while conservatives clamored for the Nobel Foundation to revoke her award. Stoll himself pointed out that even if the details were incorrect or exaggerated, the human rights abuses by the Guatemalan government were very real, and the executions happened whether Menchu actually witnessed them or not. As for Menchu herself, she initially denied that she had fabricated anything, but she later acknowledged that she might have exaggerated certain aspects of her life story. Still an Activist and Hero There is no question that Menchu’s credibility took a serious hit because of Stoll’s book and a subsequent investigation by The New York Times that turned up even more inaccuracies. Nevertheless, she has remained active in native rights movements and is a hero to millions of impoverished Guatemalans and oppressed natives all over the world. She continues to make the news. In September 2007, Menchu was a presidential candidate in her native Guatemala, running with the support of the Encounter for Guatemala Party. She won only about 3 percent of the vote (sixth place out of 14 candidates) in the first round of elections, so she failed to qualify for the run-off, which was eventually won by Alvaro Colom.

Analysis Of Dickinson s Poem The Bible - 924 Words

Dickinson’s poem 1545 contains multiple meanings and interpretations. It is a criticism of Christianity, however, she criticizes in a rather witty way. Throughout this piece of literature, she uses words that have many meanings to dig at the bible and people’s narrow-minded beliefs within the sacred text. Dickenson also uses repetition to draw attention to certain words. Perhaps the ultimate gibe is that she takes seemingly long, complicated, and popular biblical stories and shortens them to four words or less. By doing this she gives off the impression that the â€Å"faded men† who wrote the bible are not as clever as they think; but rather they’re stories are simple and transparent. Upon reading the first sentence, the reader can see that this poem is a criticism of Christianity. Dickinson writes: â€Å"The Bible is an antique volume written by faded men†¦Ã¢â‚¬  (lines1-2). The word â€Å"antique† references something that belongs to the pa st or something that is not modern. Dickinson then proceeds to call the men who wrote the Bible â€Å"faded†, which further solidifies her position that the Bible is becoming irrelevant. She also references â€Å"holy spectres† (line 3) in the next line, which can be taken one of two ways. A specter refers to a ghost or a spirit; so the first interpretation is that Dickinson is merely stating that the men who wrote the Bible were influenced by the Holy Spirit. However, a less obvious interpretation, is that â€Å"holy spectres† is a pun for Holy Scriptures. This line,Show MoreRelatedCharles Bukowski s Poem, A Genius, And Power Of The Human Mind1513 Words   |  7 PagesCharles Bukowski’s poem, â€Å"A Genius in the Crowd,† he speaks pessimistically about the human brain and disrespects the good that comes from it, yet does not hold back on describing its power. He uses dark, extreme examples to describe hidden truths in today s society. In Emily D ickinson’s poem, â€Å"[The Brain—is wider than the Sky—],† she talks about the power of the human brain, complimenting and respecting it to things thought to be incomparable. Both Dickinson’s and Bukowski’s poems show the strengthRead MoreAnalysis Of Emily Dickinson s A Narrow Fellow 1488 Words   |  6 PagesNarrow Fellow in the Grass† by Emily Dickinson is a poem that deals with her inner self. The poem was wrote in 1865 under anonymously under the title â€Å"The Snake†. The style of writing that Dickinson uses was more on how natural world is portrayed by examines one of nature’s creatures that human do not like, and that the snake. However in this poem it looks into her inner thought about how life and nature can cause one to have bitter and sweet emotional. 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Facilitation of Conditioned Fear Extinction Free Essays

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. We will write a custom essay sample on Facilitation of Conditioned Fear Extinction or any similar topic only for you Order Now 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 a Key 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 dependency. 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: ktlu@cc. 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, PD98059 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 blocks 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 antagonists 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 direc t 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 chambers 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 trials 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-po tentiated 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 receive 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-extinction 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 effect 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 used. 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 cemen ted 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 accelerated 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 dissolved 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 mi n 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 pyrophosphate, 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 group 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 to xicity, 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-dependent 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; Walker 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 Histology Rats 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 trainin g. 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 with 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 learn ing 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, bilaterally) 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 to 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-amygdala 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 translation 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 facilitation 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 extinct ion of conditioned fear. Experiment 6: the disruptive effect of intra-amygdala infusion of actinomycin D and anisomycin 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 g roup 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 received 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 inci dental 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 fe ar, 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 signi? 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. Yang 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 placeme nts 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 indicated 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 contrast 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 (Falls 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 (J avitt 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 found 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 were 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 or iginal 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 central 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. 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Self Reliance Essay Example For Students

Self Reliance Essay The essay Self-Reliance, by Ralph Waldo Emerson, is a persuasive essay promoting the ways of transcendentalism. He uses this paper to advance a major point using a structure that helps his argument. In the paper, Emerson begins his concluding thoughts with a statement that greater self-reliance will bring a revolution. He then applies this idea to society and all of its aspects, including religion, education, and art. This brings Emerson to a new, more precise focus on how society never advance, rather it recedes on one side as fast as it gains on the other. This shocking, yet intriguing, idea is supported and augmented using tone, metaphor, example, and the consequence of ignoring his opinion. The final result is a conglomeration of ideas into the major points that, Nothing can bring you peace but yourself. Nothing can bring you peace but the triumph of principles. With the major points and devices used by Emerson defined, it is now possible to examine in greater detail how he persu ades the reader, starting with the use of tone. The use of word choice, sentence length and structure, as well as many other factors set the tone of this paper. The final result is a paper that has a conciliatory tone. A paper written in this authoritative style is helpful in persuasion. It pulls the reader into the authors ideas, making them your own. The tone of the paper thus allows for metaphors to be extremely powerful in promoting Emersons ideas. The metaphors are numerous throughout the paper, however there is one indelible one towards the end of the paper that really helps to shape the essay. Society is a wave. The wave move onward, but the water of which it is composed does not. The clear metaphor of society to the wave and the particles of water to the people distinctively demonstrates Emersons idea the society never advances. If a man is not self-confident and is unable to share himself with others, as people die so too does their experience. But the ability to be self-reliant eliminates this loss of experience. Although this metaphor is strong enough on its own to provide all of the support necessary for the idea that society never advances, Emerson adds to it and his other ideas with examples. The first examples are used to support the lack of progression of society. The civilized man of the Americas and Europe is compared to the savages of New Zealand. It is here that Emerson brings into question the digression in physical strength of men as he makes advances. These advances do just as much harm as good, making man lazy and indolent. Other areas that Emerson scrutinizes are the loss of skills that only years ago were essential, such as the ability to tell time by the sun, and the loss of attention to detail. With Emersons ideas clearly imbedded in our mind, and added by his style of inductive writing, he uses the consequences of ignoring him as the final blow in this battle to persuade. Although no consequence is clearly defined, Emerson has made it more than clear what will happen if people do not become more individualistic. Society will stay as it is, no matter how many technological advances are made. This fear of being no better nor advanced than previous eras is the most powerful motivator for change of all. Emersons challenge to not rely on fortune, rather to make things happen for yourself is exactly what he want it to be, motivational and persuasive. The promotion of transcendentalism in Emersons essay Self-Reliance is the promotion of a way of better living according to Emerson. The structural support of self-reliance in Self-Reliance through tone, metaphor, example, and the consequence of ignoring Emersons opinion achieves the goal of persuasion. This produces the final result of a vote for independence, telling that Nothing can bring you peace but yourself. Nothing can bring you peace but the triumph of principles. The promise of the transcendentalist of personal peace with the achievement of self-reliance would be nothing more than an outlandish idea without Emersons ability to structure and support his idea.