Amygdala operates by analyzing incoming information and triggering defensive responses. The first question of our investigation is how amygdala distinguishes, at the synaptic level, between signals which arrive from different areas of the brain, those which process sensory information, and those which provide executive control. To address this question, one needs to interrogate a specific input by selectively stimulating fibers coming from a specific brain area. To address this question we established opsin-based techniques for selective activation or silencing of amygdala inputs from cortical area TeA which transmits sensory information, and from the anterior cingulate cortex, which is implicated in affect, pain and cognition. Both inputs target same amygdala neurons and are intermingled inside amygdala. We found significant difference in synaptic plasticity between the two pathways. While long-term potentiation of synaptic transmission (LTP) in the input from perirhinal cortex required suppression of GABAa receptor-mediated inhibition, LTP in the ACC-amygdala pathway did not. Moreover, severing connections between external capsule and amygdala enabled LTP in the input from perirhinal cortex even in the presence of GABAa receptor-mediated inhibition. In addition, we found that these two inputs exhibit differential connectivity to the amygdala inhibitory neurons. The ACC input was more effective in activating interneurons that express serotonin receptor 3, whereas the TeA input was more effective in recruiting the pericapsular cells. These findings have interesting implications: first, dopamine-dependent inhibitory neurons of the external capsule appear to gate plasticity in the amygdala input from perirhinal cortex, whereas serotonin-dependent interneurons inside the basolateral nucleus gate the highly refined information from ACC. Our current goal is to determine how the same amygdala inputs modulate fear behaviors in free-moving animals. In addition, we are investigating how amygdala interneurons gate the incoming sensory information and contribute in generation of defensive response.

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U.S. National Institute of Mental Health
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