Neuron
Volume 110, Issue 8, 20 April 2022, Pages 1400-1415.e6
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Article
Hypothalamus-habenula potentiation encodes chronic stress experience and drives depression onset

https://doi.org/10.1016/j.neuron.2022.01.011Get rights and content
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Highlights

  • LH is the most physiologically relevant input onto LHb in response to stress

  • LH fires with a unique pattern under stress that drives LHb burst

  • Repeated EPSP-burst pairings at LH-LHb pathway induce LTP

  • Emotional status can be incepted in naive mice by LH-LHb synaptic potentiation

Summary

Chronic stress is a major risk factor for depression onset. However, it remains unclear how repeated stress sculpts neural circuits and finally elicits depression. Given the essential role of lateral habenula (LHb) in depression, here, we attempt to clarify how LHb-centric neural circuitry integrates stress-related information. We identify lateral hypothalamus (LH) as the most physiologically relevant input to LHb under stress. LH neurons fire with a unique pattern that efficiently drives postsynaptic potential summation and a closely followed LHb bursting (EPSP-burst pairing) in response to various stressors. We found that LH-LHb synaptic potentiation is determinant in stress-induced depression. Mimicking this repeated EPSP-burst pairings at LH-LHb synapses by photostimulation, we artificially induced an “emotional status” merely by potentiating this pathway in mice. Collectively, these results delineate the spatiotemporal dynamics of chronic stress processing from forebrain onto LHb in a pathway-, cell-type-, and pattern-specific manner, shedding light on early interventions before depression onset.

Keywords

chronic stress
depression onset
lateral hypothalamus
lateral habenula
synaptic potentiation
Hebbian rule
emotional status

Data and code availability

  • All data reported in this paper will be shared by the lead contact upon request.

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

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Present address: Institut Pasteur, Neural Circuits for Spatial Navigation and Memory, Department of Neuroscience, Paris, France

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These authors contributed equally

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These authors contributed equally

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Lead contact