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

Publication date: 11 July 2017
Source:Cell Reports, Volume 20, Issue 2
Author(s): Hoyong Park, Jeehae Rhee, Seongju Lee, ChiHye Chung
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.

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Teaser

Park et al. find that long-term synaptic depression occurs in the lateral habenula after low- or moderate-frequency stimulation and DHPG application. In a depression model, CB1R-dependent LFS- and DHPG-LTD, but not MFS-LTD, were completely abolished. Stress exposure impairs CB1R signaling, leading to the abnormal activation of CaMKII and PKA.


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