PMID- 31548367 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20210618 IS - 2373-2822 (Electronic) IS - 2373-2822 (Linking) VI - 7 IP - 2 DP - 2020 Mar/Apr TI - Chronic Ethanol Differentially Modulates Glutamate Release from Dorsal and Ventral Prefrontal Cortical Inputs onto Rat Basolateral Amygdala Principal Neurons. LID - ENEURO.0132-19.2019 [pii] LID - 10.1523/ENEURO.0132-19.2019 [doi] AB - The medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) have strong reciprocal connectivity. Projections from the BLA to the mPFC can drive innate, anxiety-related behaviors, but it is unclear whether reciprocal projections from the mPFC to BLA have similar roles. Here, we use optogenetics and chemogenetics to characterize the neurophysiological and behavioral alterations produced by chronic ethanol exposure and withdrawal on dorsal mPFC (dmPFC) and ventral mPFC (vmPFC) medial prefrontal cortical terminals in the BLA. We exposed adult male Sprague Dawley rats to chronic intermittent ethanol (CIE) using vapor chambers, measured anxiety-like behavior on the elevated zero maze, and used electrophysiology to record glutamatergic and GABAergic responses in BLA principal neurons. We found that withdrawal from a 7 d CIE exposure produced opposing effects at dmPFC (increased glutamate release) and vmPFC (decreased glutamate release) terminals in the BLA. Chemogenetic inhibition of dmPFC terminals in the BLA attenuated the increased anxiety-like behavior we observed during withdrawal. These data demonstrate that chronic ethanol exposure and withdrawal strengthen the synaptic connections between the dmPFC and BLA but weakens the vmPFC-BLA pathway. Moreover, facilitation of the dmPFC-BLA pathway during withdrawal contributes to anxiety-like behavior. Given the opposing roles of dmPFC-BLA and vmPFC-BLA pathways in fear conditioning, our results suggest that chronic ethanol exposure simultaneously facilitates circuits involved in the acquisition of and diminishes circuits involved with the extinction of withdrawal-related aversive behaviors. CI - Copyright (c) 2020 McGinnis et al. FAU - McGinnis, Molly M AU - McGinnis MM AD - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157. FAU - Parrish, Brian C AU - Parrish BC AD - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157. FAU - Chappell, Ann M AU - Chappell AM AUID- ORCID: 0000-0002-0614-2574 AD - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157. FAU - Alexander, Nancy J AU - Alexander NJ AUID- ORCID: 0000-0003-4451-4874 AD - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157. FAU - McCool, Brian A AU - McCool BA AUID- ORCID: 0000-0002-1002-9435 AD - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157 Bmccool@wakehealth.edu. LA - eng GR - P50 AA026117/AA/NIAAA NIH HHS/United States GR - R21 AA026572/AA/NIAAA NIH HHS/United States GR - R01 AA023999/AA/NIAAA NIH HHS/United States GR - T32 AA007565/AA/NIAAA NIH HHS/United States GR - F31 AA025514/AA/NIAAA NIH HHS/United States GR - R01 AA014445/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200306 PL - United States TA - eNeuro JT - eNeuro JID - 101647362 RN - 3K9958V90M (Ethanol) RN - 3KX376GY7L (Glutamic Acid) SB - IM MH - Amygdala MH - Animals MH - *Basolateral Nuclear Complex MH - Ethanol MH - Glutamic Acid MH - Male MH - Neurons MH - Prefrontal Cortex MH - Rats MH - Rats, Sprague-Dawley PMC - PMC7070451 OTO - NOTNLM OT - infralimbic OT - patch-clamp electrophysiology OT - prelimbic OT - presynaptic EDAT- 2019/09/25 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/03/04 CRDT- 2019/09/25 06:00 PHST- 2019/04/05 00:00 [received] PHST- 2019/05/12 00:00 [revised] PHST- 2019/08/23 00:00 [accepted] PHST- 2019/09/25 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2019/09/25 06:00 [entrez] PHST- 2020/03/04 00:00 [pmc-release] AID - ENEURO.0132-19.2019 [pii] AID - eN-NWR-0132-19 [pii] AID - 10.1523/ENEURO.0132-19.2019 [doi] PST - epublish SO - eNeuro. 2020 Mar 6;7(2):ENEURO.0132-19.2019. doi: 10.1523/ENEURO.0132-19.2019. Print 2020 Mar/Apr.