Lalive Arnaud L, Congiu Mauro, Lewis Christopher, Groos Dominik, Clerke Joseph A, Tchenio Anna, Ge Yuan, Helmchen Fritjof, Mameli Manuel
Department of Fundamental Neuroscience, The University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland.
Brain Research Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Curr Biol. 2022 Apr 25;32(8):1829-1836.e4. doi: 10.1016/j.cub.2022.02.035. Epub 2022 Mar 7.
The lateral habenula (LHb) supports learning processes enabling the prediction of upcoming rewards. While reward-related stimuli decrease the activity of LHb neurons, whether this anchors on synaptic inhibition to guide reward-driven behaviors remains poorly understood. Here, we combine in vivo two-photon calcium imaging with Pavlovian conditioning in mice and report that anticipatory licking emerges along with decreases in cue-evoked calcium signals in individual LHb neurons. In vivo multiunit recordings and pharmacology reveal that the cue-evoked reduction in LHb neuronal firing relies on GABA-receptor activation. In parallel, we observe a postsynaptic potentiation of GABA-receptor-mediated inhibition, but not excitation, onto LHb neurons together with the establishment of anticipatory licking. Finally, strengthening or weakening postsynaptic inhibition with optogenetics and GABA-receptor manipulations enhances or reduces anticipatory licking, respectively. Hence, synaptic inhibition in the LHb shapes reward anticipation.
外侧缰核（LHb）支持学习过程，使机体能够预测即将到来的奖励。虽然与奖励相关的刺激会降低LHb神经元的活性，但这种现象是否基于突触抑制来引导奖励驱动行为仍知之甚少。在这里，我们将体内双光子钙成像与小鼠的巴甫洛夫条件反射相结合，并报告预期舔舐行为的出现与单个LHb神经元中线索诱发的钙信号减少同时发生。体内多单元记录和药理学研究表明，线索诱发的LHb神经元放电减少依赖于GABA受体激活。同时，我们观察到GABA受体介导的对LHb神经元的抑制（而非兴奋）的突触后增强，以及预期舔舐行为的建立。最后，通过光遗传学和GABA受体操作增强或减弱突触后抑制，分别增强或减少了预期舔舐行为。因此，LHb中的突触抑制塑造了奖励预期。
