title: 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.
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University School of Medicine, Washington, DC 20007, USA; Interdisciplinary Program in Neuroscience, Georgetown University School of Medicine, Washington, DC 20007, USA. Electronic address: jp374@georgetown.edu.
authors.forename: John G
authors.initials: JG
authors.lastname: Partridge
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University School of Medicine, Washington, DC 20007, USA; Interdisciplinary Program in Neuroscience, Georgetown University School of Medicine, Washington, DC 20007, USA.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Forcelli
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University School of Medicine, Washington, DC 20007, USA.
authors.forename: Ruixi
authors.initials: R
authors.lastname: Luo
authors.affiliation: Department of Biology, Georgetown University School of Medicine, Washington, DC 20007, USA.
authors.forename: Jonah M
authors.initials: JM
authors.lastname: Cashdan
authors.affiliation: Interdisciplinary Program in Neuroscience, Georgetown University School of Medicine, Washington, DC 20007, USA; Department of Obstetrics & Gynecology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Schulkin
authors.affiliation: Abramson Pediatric Research Center, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Rita J
authors.initials: RJ
authors.lastname: Valentino
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University School of Medicine, Washington, DC 20007, USA; Interdisciplinary Program in Neuroscience, Georgetown University School of Medicine, Washington, DC 20007, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vicini
mesh_terms: D000818:Animals; D066274:Central Amygdaloid Nucleus / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis* / Q000172:deficiency; D005260:Female; D059330:GABAergic Neurons / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D012686:Septal Nuclei / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid; D003346:Corticotropin-Releasing Hormone
keywords: ChR2; Chronic unpredictable stress; Corticotropin releasing factor; GABA