GHSR1a deficiency suppresses inhibitory drive on dCA1 pyramidal neurons and contributes to memory reinforcement.

Autor:	Li N; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao University, 308 Ningxia Rd, Qingdao, Shandong, 266071, China.; Department of Medicine, Qingdao Binhai University, 425 West Jialing River Rd, Qingdao, Shandong, 266555, China., Li N; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao University, 308 Ningxia Rd, Qingdao, Shandong, 266071, China.; Department of Health and Life Sciences, University of Health and Rehabilitation Sciences, 17 Shandong Rd, Qingdao, Shandong, 266000, China., Yang L; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao University, 308 Ningxia Rd, Qingdao, Shandong, 266071, China., Gu H; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao University, 308 Ningxia Rd, Qingdao, Shandong, 266071, China., Ji J; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao University, 308 Ningxia Rd, Qingdao, Shandong, 266071, China., Zhou H; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao University, 308 Ningxia Rd, Qingdao, Shandong, 266071, China., Zhu Q; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao University, 308 Ningxia Rd, Qingdao, Shandong, 266071, China., Yu M; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao University, 308 Ningxia Rd, Qingdao, Shandong, 266071, China.; Department of Health and Life Sciences, University of Health and Rehabilitation Sciences, 17 Shandong Rd, Qingdao, Shandong, 266000, China., Sun Y; Department of Nutrition, Texas A&M University, 750 Agronomy Rd, College Station, TX, 77843, United States., Zhou Y; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao University, 308 Ningxia Rd, Qingdao, Shandong, 266071, China.; Department of Health and Life Sciences, University of Health and Rehabilitation Sciences, 17 Shandong Rd, Qingdao, Shandong, 266000, China.; Department of Physiology, Institute of Brain Sciences and Related Disorders, Qingdao University, 308 Ningxia Rd., Qingdao, Shandong, 266071, China.; Department of rehabilitation medicine, Affiliated Hospital of Qingdao University, 16 Jiangsu Rd., Qingdao, Shandong, 266000, China.
Jazyk:	angličtina
Zdroj:	Cerebral cortex (New York, N.Y. : 1991) [Cereb Cortex] 2023 Mar 10; Vol. 33 (6), pp. 2612-2625.
DOI:	10.1093/cercor/bhac230
Abstrakt:	Growth hormone secretagogue receptor 1a (GHSR1a)-the receptor for orexigenic hormone ghrelin-is a G protein-coupled receptor that is widely distributed in the brain, including the hippocampus. Studies have demonstrated that genetic deletion of GHSR1a affects memory, suggesting the importance of ghrelin/GHSR1a signaling in cognitive control. However, current reports are controversial, and the mechanism underlying GHSR1a modulation of memory is uncertain. Here, we first report that global GHSR1a knockout enhances hippocampus-dependent memory, facilitates initial LTP in dorsal hippocampal Schaffer Collateral-CA1 synapses, and downregulates Akt activity in the hippocampus. Moreover, we show that the intrinsic excitability of GAD67+ interneurons-rather than neighboring pyramidal neurons in the dCA1-is suppressed by GHSR1a deletion, an effect that is antagonized by acute application of the Akt activator SC79. In addition, the inhibitory postsynaptic currents (IPSCs) on dCA1 pyramidal neurons are selectively reduced in mice with a GHSR1a deficiency. Finally, we demonstrate that selectively increasing the excitability of parvalbumin-expressing interneurons by hM3Dq-DREADDs increases IPSCs on dCA1 pyramidal neurons and normalizes memory in Ghsr1a KO mice. Our findings thus reveal a novel mechanism underlying memory enhancement of GHSR1a deficiency and herein support an adverse effect of GHSR1a signaling in hippocampus-dependent memory processes. (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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