Circuit Based Analysis of Fear and Stress

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This project investigates structural and molecular synaptic plasticity in the circuits mediating fear conditioning (FC), related circuits affected by stress, and the synaptic basis for fear/stress interactions. These experiments will be done in collaboration with Projects 1, 4, and the QMC. Synaptic basis of FC. The convergent projections to lateral amygdala (LA) from the medial geniculate nucleus (MGn) and auditory cortex (AC) will be labeled through anterograde transport and analyzed ultrastructurally in fear conditioned and control (unpaired stimuli) animals. Quantitative immunogold will be used to develop a molecular profile of the synapses mediating FC. We hypothesize that the molecular profile of the synapse will be altered by FC. Neuronal reconstructions will also be carried out in LA to determine the effects of FC on dendritic arbor, spine number, and morphology. We hypothesize that molecular synaptic alterations will predominate over structural alterations as mediators of FC. Synaptic alterations from stress. We hypothesize that chronic and acute behavioral stress will result in synaptic alterations in both amygdala and the medial prefrontal cortex (mPFC) and that stress-induced alterations will be manifested in both mPFC/BA circuits and the auditory circuits that mediate FC. The impact of chronic or acute stress on the molecular profile of key synapses and dendrites morphology will be assessed for both sets of circuits. Spine number will be assessed stereologically in both LA and BA, to determine the nuclear target of the stress-induced spine increase. An analysis of dendritic arborization, spine density, and spine morphology will be done on the neurons that reciprocally connect mPFC and BA, as well as neurons in LA. These studies will determine the circuits that are directly affected by stress that might impact FC. Interactions between stress and FC. Animals that have had FC and exposed to stress will be analyzed with the same ultrastructural and morphologic approaches outlined above to directly assess the interactive synaptic effects. In addition, we will determine whether inactivation of the amygdata blocks the stress-induced plasticity in mPFC, as such inactivation does block FC.