2. Academic Validation
  3. Noninvasive tactile stimulation engaging a thalamic-amygdala circuit ameliorates mood dysfunction in mouse models of depression-like behavior

Noninvasive tactile stimulation engaging a thalamic-amygdala circuit ameliorates mood dysfunction in mouse models of depression-like behavior

  • Neuron. 2026 Apr 1:S0896-6273(26)00176-5. doi: 10.1016/j.neuron.2026.03.012.
Hong-Wei Fan 1,  Qi-Han He 1,  Jie-Qun Zheng 1,  Lan-Fang Li 1,  Jia-Jie Chen 2,  Li Yin 1,  Yi-Lin Zhong 1,  Ping Zhang 3,  Xin-Ran Xu 3,  Heng-Ye Man 4,  You-Ming Lu 1,  Zhou-Ping Tang 3,  Xiao-Dong Liu 5,  Ling-Qiang Zhu 6,  Dan Liu 7
Affiliations

Affiliations

  • 1 Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
  • 2 Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Department of Biology, Boston University, Boston, MA 02215, USA.
  • 5 Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, Shatin 999077, China.
  • 6 Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. Electronic address: [email protected].
  • 7 Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. Electronic address: [email protected].
PMID: 41928509 DOI: 10.1016/j.neuron.2026.03.012
Abstract

Disruption of excitatory/inhibitory (E/I) balance within the basolateral amygdala (BLA) is a critical feature of depressive and anxiety-like states, yet effective circuit-based therapies are lacking. Here, we demonstrate that tactile experience enrichment (TEE)-a noninvasive sensory stimulation-ameliorates depressive- and anxiety-like behaviors in multiple post-stroke depression (PSD) mouse models by engaging a thalamic-amygdala pathway from the reuniens nucleus (Re) to BLA inhibitory neurons (ReExc-BLAInh). Activation of this compensatory circuit re-establishes E/I balance in the BLA through feedforward inhibition of excitatory neurons, thereby bypassing the impaired medial prefrontal cortex-BLA pathway. Both chemogenetic activation of the ReExc-BLAInh pathway and TEE treatment in chronic social defeat stress (CSDS) and chronic restraint stress (CRS) models similarly restore synaptic E/I balance and significantly improve emotional behaviors. These results define a lesion-bypassing circuit mechanism through which tactile input modulates amygdala function in mice and will motivate future studies of translational relevance.

Keywords

E/I balance; basolateral amygdala; depression; stroke; tactile experience enrichment.

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