4.2 Article

Output-Specific Adaptation of Habenula-Midbrain Excitatory Synapses During Cocaine Withdrawal

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FRONTIERS IN SYNAPTIC NEUROSCIENCE
卷 13, 期 -, 页码 -

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FRONTIERS MEDIA SA
DOI: 10.3389/fnsyn.2021.643138

关键词

ventral tegmental area; lateral habenula; cocaine; synaptic plasticity; glutamatergic transmission

资金

  1. Swiss National Fund [31003A]
  2. Eberhard Karls University of Tubingen
  3. Werner Reichardt Centre for Integrative Neuroscience [Deutsche Forschungsgemeinschaft (DFG)] [EXC 307]
  4. DFG [BU3126/1-1, BU3126/2-1]

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The study found that cocaine withdrawal induces discrete and opposing synaptic adaptations from the lateral habenula (LHb) onto ventral tegmental area (VTA) neurons in mice. Different subsets of VTA neurons receive varied synaptic changes in response to LHb input during cocaine withdrawal.
Projections from the lateral habenula (LHb) control ventral tegmental area (VTA) neuronal populations' activity and both nuclei shape the pathological behaviors emerging during cocaine withdrawal. However, it is unknown whether cocaine withdrawal modulates LHb neurotransmission onto subsets of VTA neurons that are part of distinct neuronal circuits. Here we show that, in mice, cocaine withdrawal, drives discrete and opposing synaptic adaptations at LHb inputs onto VTA neurons defined by their output synaptic connectivity. LHb axons innervate the medial aspect of VTA, release glutamate and synapse on to dopamine and non-dopamine neuronal populations. VTA neurons receiving LHb inputs project their axons to medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and lateral hypothalamus (LH). While cocaine withdrawal increases glutamate release from LHb onto VTA-mPFC projectors, it reduces presynaptic release onto VTA-NAc projectors, leaving LHb synapses onto VTA-to-LH unaffected. Altogether, cocaine withdrawal promotes distinct adaptations at identified LHb-to-VTA circuits, which provide a framework for understanding the circuit basis of the negative states emerging during abstinence of drug intake.

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