Auditory fear memory is thought to be maintained by fear conditioning-induced potentiation of synaptic efficacy, which involves enhanced expression of surface AMPA receptor (AMPAR) at excitatory synapses in the lateral amygdala (LA). Depotentiation, reversal of conditioning-induced potentiation, has been proposed as a cellular mechanism for fear extinction; however, a direct link between depotentiation and extinction has not yet been tested. To address this issue, we applied both ex vivo and in vivo approaches to rats in which fear memory had been consolidated. A unique form of depotentiation reversed conditioning-induced potentiation at thalamic input synapses onto the LA (T-LA synapses) ex vivo. Extinction returned the enhanced T-LA synaptic efficacy observed in conditioned rats to baseline and occluded the depotentiation. Consistently, extinction reversed conditioning-induced enhancement of surface expression of AMPAR subunits in LA synaptosomal preparations. A GluR2-derived peptide that blocks regulated AMPAR endocytosis inhibited depotentiation, and microinjection of a cell-permeable form of the peptide into the LA attenuated extinction. Our results are consistent with the use of depotentiation to weaken potentiated synaptic inputs onto the LA during extinction and provide strong evidence that AMPAR removal at excitatory synapses in the LA underlies extinction.lateral amygdala ͉ fear conditioning ͉ AMPA receptor ͉ endocytosis T he cortical and thalamic input synapses onto the lateral amygdala (LA) (C-LA and T-LA synapses, respectively) carry auditory information from the auditory cortex and auditory thalamus onto the LA, respectively (1). Long-term potentiation (LTP; an in vitro model of memory) (2)-like changes in these pathways are thought to underlie both the encoding and consolidation of auditory fear memory (3-8). The results of a recent study suggest that long-term retention of conditioning-induced potentiation at excitatory synapses in the LA is a critical requirement for consolidated fear memory within the LA (7, 9). Also, LTP requiring the synaptic delivery of AMPA receptors (AMPARs) at excitatory synapses in the LA appears to be necessary for establishing consolidated fear memory (6,8,10). Conditioning-induced potentiation and auditory fear memory encoded in the LA have been shown to be consolidated within 24 h after fear conditioning (5, 7, 11). Moreover, auditory fear memory appears to be maintained in the LA across the adult lifetime of rats (12). Thus, consolidation of auditory fear memory encoded in the LA is rapid and localized, unlike hippocampus-dependent memory, which involves slow and distributed consolidation processes (13).In the present study, we tested the hypothesis that depotentiation of conditioning-induced potentiation at excitatory synapses in the LA underlies extinction of consolidated fear memory. Synaptic weights were monitored ex vivo by using whole-cell (or field potential) recordings in amygdala slices prepared from behaviortrained rats. Results Extinction of Consolidated ...

Stress in adulthood can have a profound effect on physiology and behavior, but the extent to which prolonged maternal stress affects the brain function of offspring when they are adult remains primarily unknown. In the present work, chronic immobilization stress to pregnant mice affected fetal growth and development. When pups born from stressed mice were reared to adulthood in an environment identical to that of nonstressed controls, several physiological parameters were essentially unaltered. However, spatial learning and memory was significantly impaired in the maternally stressed offspring in adulthood. Furthermore, electrophysiological examination revealed a significant reduction in NMDA receptor-mediated long-term potentiation in the CA1 area of hippocampal slices. Subsequent biochemical analysis demonstrated a substantial decrease in NR1 and NR2B subunits of the NMDA receptor in synapses of the hippocampus, and the interaction between these two subunits appeared to be reduced. These results suggest that prolonged maternal stress leads to long-lasting malfunction of the hippocampus, which extends to and is manifested in adulthood.

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The experiments of this study demonstrate that relatively modest rates of repetitive tactile stimulation are accompanied by rapid and reversible modifications (either increases or decreases) in the response of SI neurons. Complete recovery occurs in a few minutes following cessation of stimulation. The modifications are reproducible (1) if stimulus parameters remain the same and (2) if time for recovery is provided between successive exposures. In contrast, repetitive tactile stimuli identical to those that modify SI neuron response rarely lead to changes in the response of cutaneous mechanoreceptive afferents. SI neuron functional properties conventionally regarded as immutable [e.g., directional selectivity, and distribution of sensitivity within the receptive field (RF)] also modify with repetitive stimulation. While the changes in RF organization differ in detail from one neuron to the next, they are similar in form: the response generated by stimulus contact with one (or more rarely, several) RF region(s) becomes enhanced relative to the response the same stimulus evokes from neighboring regions. Neurons in the same column (sampled in the same radial penetration) exhibit very similar changes in the distribution of sensitivity within the RF, whereas neurons sampled in tangential penetrations exhibit diverse, apparently unrelated changes in RF organization in response to the same repetitive stimulus. Simultaneous multichannel recordings reveal that a repetitive tactile stimulus exerts similar effects on the response and RFs of the neurons within local (no more than 100 microns) neuron groupings. A model that incorporates a manner of SI topographical organization (segregate organization) and well-known aspects of neocortical cellular, neurotransmitter/receptor, and connectional architecture accounts for the changes in SI neuron behavior observed during repetitive stimulation.

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