Stress increases GABAergic neurotransmission in CRF neurons of the central amygdala and bed nucleus stria terminalis

Abstract

Corticotrophin Releasing Factor (CRF) is a critical stress-related neuropeptide in major output pathways of the amygdala, including the central nucleus (CeA), and in a key projection target of the CeA, the bed nucleus of the stria terminalis (BnST). While progress has been made in understanding the contributions and characteristics of CRF as a neuropeptide in rodent behavior, little attention has been committed to determine the properties and synaptic physiology of specific populations of CRF-expressing (CRF+) and non-expressing (CRF−) neurons in the CeA and BnST. Here, we fill this gap by electrophysiologically characterizing distinct neuronal subtypes in CeA and BnST. Crossing tdTomato or channelrhodopsin-2 (ChR2-YFP) reporter mice to those expressing Cre-recombinase under the CRF promoter allowed us to identify and manipulate CRF+ and CRF− neurons in CeA and BnST, the two largest areas with fluorescently labeled neurons in these mice. We optogenetically activated CRF+ neurons to elicit action potentials or synaptic responses in CRF+ and CRF− neurons. We found that GABA is the predominant co-transmitter in CRF+ neurons within the CeA and BnST. CRF+ neurons are highly interconnected with CRF− neurons and to a lesser extent with CRF+ neurons. CRF+ and CRF− neurons differentially express tonic GABA currents. Chronic, unpredictable stress increase the amplitude of evoked IPSCs and connectivity between CRF+ neurons, but not between CRF+ and CRF− neurons in both regions. We propose that reciprocal inhibition of interconnected neurons controls CRF+ output in these nuclei.