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Shona Chattarji

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India


Friday 27 October 2006, 14:00

Seminar Room B10 (Basement)

Alexandra House, 17 Queen Square, London, WC1N 3AR


Silent synapses speak up in the amygdala: 'good plasticity' in a 'bad neighborhood'


Why are memories of emotional events often more powerful and persistent than factual ones? Stress disorders bring this question into sharp focus because severe stress has contrasting effects on these two types of memory. Stress impairs hippocampal memories of facts and events, while it amplifies amygdala-dependent emotional memories. Therefore, we have used animal models of stress to investigate the synaptic basis of this contrast. Chronic immobilization stress causes dendritic growth and spinogenesis, thereby enhancing the structural basis of synaptic connectivity in principal neurons of the lateral amygdala (LA) in rats. Next, using whole-cell recordings in amygdalar slices, we find that chronic stress, in addition to reducing spontaneous and evoked inhibitory currents, amplifies the ratio of NMDA to AMPA EPSCs evoked by activating thalamic inputs to LA. Further, the ratio of coefficient of variation (CV) is significantly smaller in stress-treated cells when the CV of evoked AMPA and NMDA EPSCs is compared in the same cell. This decrease in CV ratio in stressed neurons is caused by a reduction in the CV of NMDA EPSCs, and not by an increase in the CV of AMPA EPSCs. Using analysis of mixed mEPSC with AMPA and NMDA components, we also failed to detect any stress-induced difference in the ratio of NMDA and AMPA mEPSC amplitudes. Since this analysis was based on detecting AMPA-containing events, the lack of stress effects on mEPSC ratios suggests that the increase in evoked NMDA currents is mediated largely by NMDA-only synapses on newly formed spines. These data suggest that exposure to chronic stress forms silent synapses in the amygdala, which in turn could enhance their capacity for subsequent potentiation.


This prediction was confirmed in two ways. First, we find that stress enhances NMDA-dependent LTP in the LA. Second, in an auditory fear conditioning paradigm, the same pairing of tone with weak footshock that has relatively little impact on unstressed animals causes abnormally high levels of fear in previously stressed animals. Thus, prolonged stress may leave its mark in the amygdala by forming new synapses with greater capacity for subsequent potentiation, thereby creating an ideal synaptic substrate for emotional symptoms of stress disorders. Ironically, earlier studies have established the same electrophysiological and structural metrics as facilitators of long-term synaptic plasticity mechanisms underlying hippocampal memories. Behavioral stress appears to elicit similar 'good' plasticity mechanisms in the amygdala, but with debilitating functional consequences.