TY - JOUR T1 - CART neuropeptide modulates the extended amygdalar CeA-vBNST circuit to gate expression of innate fear JF - bioRxiv DO - 10.1101/096610 SP - 096610 AU - Abhishek Rale AU - Ninad Shendye AU - Nishikant Subhedar AU - Aurnab Ghose Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/12/26/096610.abstract N2 - Innate fear is critical for the survival of animals and is under tight homeostatic control. Deregulation of innate fear processing is thought to underlie pathological phenotypes including, phobias and panic disorders. Although central processing of conditioned fear has been extensively studied, the circuitry and regulatory mechanisms subserving innate fear remain relatively poorly defined.In this study, we identify cocaine- and amphetamine-regulated transcript (CART) neuropeptide signalling in the central amygdala (CeA) - ventral bed nucleus of stria terminalis (vBNST) axis as a key modulator of innate fear expression. TMT, a component of fox faeces, induces a freezing response whose intensity is regulated by the extent of CART-signalling in the CeA neurons. Abrogation of CART activity in the CeA attenuates the freezing response and reduces activation of vBNST neurons. Conversely, ectopically elevated CART signalling in the CeA potentiates the fear response concomitant with enhanced vBNST activation. We show that local levels of CART signaling modulate the activation of CeA neurons by NMDA receptor mediated glutamatergic inputs, in turn, regulating activity in the vBNST.This study identifies the extended amygdalar CeA-vBNST circuit as a CART modulated axis encoding innate fear. CART signaling regulates the glutamatergic excitatory drive in the CeA-vBNST circuit, in turn, gating the expression of the freezing response to TMT. ER -