Dynamic Remodeling of Central Amygdala Glutamatergic Circuits Across Fear States: A Mechanism for Experience-Dependent Modification of Behavioral Selection
Hartley, Nolan D.
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2019-09-13
Abstract
Acquisition and extinction of learned fear responses utilize flexible yet conserved neural circuits that promote or suppress fear expression, respectively. Here we show that acquisition of passive fear behavior is associated with dynamic remodeling of synaptic excitatory drive from the basolateral amygdala (BLA) away from corticotropin releasing factor-expressing (CRF+) central lateral amygdala (CeL) neurons, while fear extinction training remodels this circuit back toward favoring CRF+ neurons. Importantly, BLA activity is required for this experience-dependent remodeling, while directed inhibition of the BLA-CeL circuit impairs both fear memory acquisition and extinction memory retrieval. Additionally, ectopic excitation of CRF+ neurons impairs memory acquisition and facilities extinction, whereas CRF+ neuron inhibition impairs extinction memory retrieval, supporting the notion that CRF+ neurons serve to inhibit learned freezing behavior. These data suggest afferent-specific dynamic remodeling of relative excitatory drive to functionally distinct subcortical neuronal-output populations represent an important mechanism underlying experience-dependent modification of behavioral selection.