Mechanistically Distinct Modes of Endocannabinoid Mobilization at Glutamatergic Synapses of the Lateral Division of the Central Amygdala and Its Regulation by Chronic Stress

Abstract

The lateral division of the central amygdala (CeAL) is a key structure at the limbic-motor interface regulating stress-responses and emotional learning. Endocannabinoid (eCB) signaling is heavily implicated in the regulation of stress-response physiology and emotional learning processes, however, the role of eCBs in the modulation of synaptic efficacy in the CeAL is not well understood. Here we describe the subcellular localization of type 1 cannabinoid receptors (CB1) and the eCB synthetic machinery at glutamatergic synapses in the CeAL and find that CeAL neurons exhibit multiple mechanistically and temporally distinct modes of postsynaptic eCB mobilization. Furthermore, this work demonstrates that following chronic stress exposure, eCB-mediated suppression of CeAL excitatory inputs is enhanced. Collectively, these data identify a prominent role for eCBs in the modulation of excitatory drive to CeAL neurons and provide insight into the mechanisms by which eCB signaling and exogenous cannabinoids could regulate stress-responses and emotional learning.