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Competitive synaptic interactions between principal neurons (PNs) with differing intrinsic excitability were recently shown to determine which dorsal lateral amygdala (LAd) neurons are recruited into a fear memory trace. Here, we explored the contribution of these competitive interactions in determining the stimulus specificity of conditioned fear associations. To this end, we used a realistic biophysical computational model of LAd that included multi-compartment conductance-based models of 800 PNs and 200 interneurons. To reproduce the continuum of spike frequency adaptation displayed by PNs, the model included three subtypes of PNs with high, intermediate, and low spike frequency adaptation. In addition, the model network integrated spatially differentiated patterns of excitatory and inhibitory connections within LA, dopaminergic and noradrenergic inputs, extrinsic thalamic and cortical tone afferents to simulate conditioned stimuli as well as shock inputs for the unconditioned stimulus. Last, glutamatergic synapses in the model could undergo activity-dependent plasticity. Our results suggest that plasticity at both excitatory (PN–PN) and di-synaptic inhibitory (PN–ITN and, particularly, ITN–PN) connections are major determinants of the synaptic competition governing the assignment of PNs to the memory trace. The model also revealed that training-induced potentiation of PN–PN synapses promotes, whereas that of ITN–PN synapses opposes, stimulus generalization. Indeed, suppressing plasticity of PN–PN synapses increased, whereas preventing plasticity of interneuronal synapses decreased the CS specificity of PN recruitment. Overall, our results indicate that the plasticity configuration imprinted in the network by synaptic competition ensures memory specificity. Given that anxiety disorders are characterized by tendency to generalize learned fear to safe stimuli or situations, understanding how plasticity of intrinsic LAd synapses regulates the specificity of learned fear is an important challenge for future experimental studies. 相似文献
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Tagore KR Krishna R Charyulu PA Latha PP 《Indian journal of pathology & microbiology》2007,50(4):835-837
Cellular schwannomas in pharyngeal region are rare. These tumors histologically mimic malignant peripheral nerve sheath tumors because of their growth pattern, high cellularity and mitotic activity, but they are relatively benign tumors with a tendency to recur but do not metastasize. 相似文献
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Diler RS Daviss WB Lopez A Axelson D Iyengar S Birmaher B 《Journal of affective disorders》2007,102(1-3):125-130
BACKGROUND: Youths with attention deficit hyperactivity disorders (ADHD) frequently have comorbid major depressive disorders (MDD) sharing overlapping symptoms. Our objective was to examine which depressive symptoms best discriminate MDD among youths with ADHD. METHODS: One-hundred-eleven youths with ADHD (5.2-17.8 years old) and their parents completed interviews with the K-SADS-PL and respective versions of the child or the parent Mood and Feelings Questionnaire (MFQ-C, MFQ-P). Controlling for group differences, logistic regression was used to calculate odds ratios reflecting the accuracy with which various depressive symptoms on the MFQ-C or MFQ-P discriminated MDD. Stepwise logistic regression then identified depressive symptoms that best discriminated the groups with and without MDD, using cross-validated misclassification rate as the criterion. RESULTS: Symptoms that discriminated youths with MDD (n=18) from those without MDD (n=93) were 4 of 6 mood/anhedonia symptoms, all 14 depressed cognition symptoms, and only 3 of 11 physical/vegetative symptoms. Mild irritability, miserable/unhappy moods, and symptoms related to sleep, appetite, energy levels and concentration did not discriminate MDD. A stepwise logistic regression correctly classified 89% of the comorbid MDD subjects, with only age, anhedonia at school, thoughts about killing self, thoughts that bad things would happen, and talking more slowly remaining in the final model. LIMITATIONS: Results of this study may not generalize to community samples because subjects were drawn largely from a university-based outpatient psychiatric clinic. CONCLUSIONS: These findings stress the importance of social withdrawal, anhedonia, depressive cognitions, suicidal thoughts, and psychomotor retardation when trying to identify MDD among ADHD youths. 相似文献
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Daptomycin nonsusceptibility in Staphylococcus aureus with reduced vancomycin susceptibility is independent of alterations in MprF 下载免费PDF全文
Pillai SK Gold HS Sakoulas G Wennersten C Moellering RC Eliopoulos GM 《Antimicrobial agents and chemotherapy》2007,51(6):2223-2225
A previous study documented the presence of mutations in mprF that accompanied the loss of daptomycin susceptibility among Staphylococcus aureus isolates following exposure to the drug. An association between the development of glycopeptide-intermediate S. aureus and daptomycin nonsusceptibility has also been recently described. We report that among three clinical S. aureus isolates which developed vancomycin heteroresistance, as well as daptomycin nonsusceptibility despite a lack of exposure to this drug, there were no mutations resulting in amino acid substitutions in MprF. 相似文献
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