The interaction between social hierarchy and depression/anxiety: Involvement of glutamatergic pyramidal neurons in the medial prefrontal cortex (mPFC)

Yong-Yu Yin; Zhao-Kai Lai; Jiao-Zhao Yan; Qian-Qian Wei; Bin Wang; Li-Ming Zhang; Yun-Feng Li

doi:10.1016/j.ynstr.2023.100536

The interaction between social hierarchy and depression/anxiety: Involvement of glutamatergic pyramidal neurons in the medial prefrontal cortex (mPFC)

Neurobiol Stress. 2023 Mar 30:24:100536. doi: 10.1016/j.ynstr.2023.100536. eCollection 2023 May.

Authors

Yong-Yu Yin¹, Zhao-Kai Lai², Jiao-Zhao Yan³, Qian-Qian Wei^{1

4}, Bin Wang¹, Li-Ming Zhang¹, Yun-Feng Li^{1

3}

Affiliations

¹ Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing, China.
² Fujian University of Traditional Chinese Medicine, Fuzhou, China.
³ Beijing Institute of Basic Medical Sciences, Beijing, China.
⁴ School of Medicine, Nantong University, Nantong, China.

Abstract

Social hierarchy greatly impacts physical and mental health, but the relationship between social hierarchy and depression/anxiety and the underlying neural mechanism remain unclear. The present study used the tube test to determine the social hierarchy status of mice and then performed several behavioral tests to evaluate depression-like and anxiety-like behaviors. Electrophysiological techniques were used to record the firing activities of glutamatergic pyramidal neurons and local field potentials in the medial prefrontal cortex (mPFC). The results suggested that the mice in each cage (4 per cage) established a stable social hierarchy after 2 weeks. Subordinate mice displayed significantly fewer pushing and advancing behaviors, and more retreat behaviors compared with dominant mice. Furthermore, subordinate mice had significantly more immobility durations in the TST, but significantly fewer distances, entries, and time into the center in the OFT, as well as significantly less percent of distances, entries, and time into the open arms in the EPMT, compared with dominant mice, which indicated that subordinate mice displayed depression- and anxiety-like behaviors. In addition, chronic restraint stress (CRS) significantly induced depression- and anxiety-like behaviors in mice and altered social dominance behaviors in the tube test. CRS mice displayed significantly fewer pushing and advancing behaviors, and more retreat behaviors compared with control mice. Furthermore, low social rank and CRS significantly decreased the firing of pyramidal neurons and γ-oscillation activity in the mPFC. Taken together, the present study revealed an inverse relationship between social hierarchy and depression/anxiety, and the neural basis underlying this association might be the excitability of pyramidal neurons and γ oscillation in the mPFC. These findings established an important foundation for a depression/anxiety model based on social hierarchy and provided a new avenue for the development of therapies for stress-related mood disorders.

Keywords: Depression; Pyramidal neurons; Social hierarchy; mPFC; γ oscillation.