한빛사논문
- 조회240
Sang Ho Yoon 1,2,4, Woo Seok Song 1,2, Geehoon Chung 1,2,5, Sang Jeong Kim 1,2 and Myoung-Hwan Kim 1,2,3,*
1Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
2Neuroscience Research Institute, Seoul National University Medical Research Center, Seoul 03080, Korea.
3Seoul National University Bundang Hospital, Seongnam, Gyeonggi 13620, Korea.
4Present address: Department of Anatomy & Neurobiology, University of California Irvine, Irvine, CA 92697, USA.
5Present address: Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.
*Corresponding author: correspondence to Myoung-Hwan Kim
Abstract
Anatomical connectivity and lesion-deficit studies have shown that the dorsal and ventral hippocampi contribute to cognitive and emotional processes, respectively. However, the role of the dorsal hippocampus (dHP) in emotional or stress-related behaviors remains unclear. Here, we showed that neuronal activity in the dHP affects stress-coping behaviors in mice via excitatory projections to the medial prefrontal cortex (mPFC). The antidepressant ketamine rapidly induced c-Fos expression in both the dorsal and ventral hippocampi. The suppression of GABAergic transmission in the dHP-induced molecular changes similar to those induced by ketamine administration, including eukaryotic elongation factor 2 (eEF2) dephosphorylation, brain-derived neurotrophic factor (BDNF) elevation, and extracellular signal-regulated kinase (ERK) phosphorylation. These synaptic and molecular changes in the dHP induced a reduction in the immobility time of the mice in the tail-suspension and forced swim tests without affecting anxiety-related behavior. Conversely, pharmacological and chemogenetic potentiation of inhibitory neurotransmission in the dHP CA1 region induced passive coping behaviors during the tests. Transneuronal tracing and electrophysiology revealed monosynaptic excitatory connections between dHP CA1 neurons and mPFC neurons. Optogenetic stimulation of dHP CA1 neurons in freely behaving mice produced c-Fos induction and spike firing in the mPFC neurons. Chemogenetic activation of the dHP-recipient mPFC neurons reversed the passive coping behaviors induced by suppression of dHP CA1 neuronal activity. Collectively, these results indicate that neuronal activity in the dHP modulates stress-coping strategies to inescapable stress and contributes to the antidepressant effects of ketamine via the dHP-mPFC circuit.
논문정보
- Research article
- 2024년 09월 (BRIC 등록일 2024-09-04)
- 국내 연구진
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