Selectively Impaired Endocannabinoid-Dependent Long-Term Depression in the Lateral Habenula in an Animal Model of Depression

Cell Reports

Jeehae Rhee¹  Seongju Lee¹  Hoyong Park¹  ChiHye Chung¹ 

[1] Department of Biological Sciences, Konkuk University, Seoul 05029, South Korea;

关键词: synaptic plasticity;    endocannabinoids;    long-term depression;    lateral habenula;    depressive disorders;   

DOI  :  10.1016/j.celrep.2017.06.049

来源: DOAJ

【 摘 要 】

Abnormal potentiation in the lateral habenula (LHb) has been suggested to mediate depression-like behaviors. However, the underlying mechanisms of the synaptic efficacy regulation of LHb synapses and the potential for their modulation are only poorly understood. Here, we report that long-term synaptic depression (LTD) occurs in the LHb upon both low-frequency stimulation (LFS) and moderate-frequency stimulation (MFS). LFS-induced LTD (LFS-LTD) is accompanied by a reduction in presynaptic release probability, which is endocannabinoid (eCB) signaling dependent. Surprisingly, exposure to an acute stressor completely masks the induction of LFS-LTD in the LHb while leaving the MFS-induced LTD intact. Pharmacological activation of cannabinoid receptor 1 (CB1R) or blockade of αCaMKII successfully restored LTD in the LHb in an animal model of depression. Thus, our findings reveal a form of synaptic strength regulation and a stress-induced shift of synaptic plasticity in the LHb.

【 授权许可】

Unknown