被盖腹侧区
多巴胺
伏隔核
神经科学
加巴能
光遗传学
有条件地点偏好
γ-氨基丁酸受体
神经元
中脑
细胞神经科学
生物
抑制性突触后电位
受体
γ-氨基丁酸受体
多巴胺能
中枢神经系统
生物化学
作者
Nicholas J. Edwards,Hugo A. Tejeda,Marco Pignatelli,Shiliang Zhang,Ross A. McDevitt,Jocelyn Wu,Caroline E. Bass,Bernhard Bettler,Marisela Morales,Antonello Bonci
摘要
Inputs to midbrain dopamine neurons control rewarding and drug-related behaviors. The authors found that nucleus accumbens inputs and local GABA neurons inhibit dopamine neurons through distinct populations of GABA receptors. Furthermore, genetic deletion of GABAB receptors from dopamine neurons selectively increased behavioral sensitivity to cocaine. Afferent inputs to the ventral tegmental area (VTA) control reward-related behaviors through regulation of dopamine neuron activity. The nucleus accumbens (NAc) provides one of the most prominent projections to the VTA; however, recent studies have provided conflicting evidence regarding the function of these inhibitory inputs. Using optogenetics, cell-specific ablation, whole cell patch-clamp and immuno-electron microscopy, we found that NAc inputs synapsed directly onto dopamine neurons, preferentially activating GABAB receptors. GABAergic inputs from the NAc and local VTA GABA neurons were differentially modulated and activated separate receptor populations in dopamine neurons. Genetic deletion of GABAB receptors from dopamine neurons in adult mice did not affect general or morphine-induced locomotor activity, but markedly increased cocaine-induced locomotion. Collectively, our findings demonstrate notable selectivity in the inhibitory architecture of the VTA and suggest that long-range GABAergic inputs to dopamine neurons fundamentally regulate behavioral responses to cocaine.
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