Ventral tegmental area glutamate neurons co-release GABA and promote positive reinforcement.

Ventral tegmental area glutamate neurons co-release GABA and promote positive reinforcement.
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DOI:
10.1038/ncomms13697
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发表时间:
2016-12-15
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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除了多巴胺神经元外,腹侧被盖区(VTA)还含有GABA、谷氨酸和共释放神经元,最近的报道表明谷氨酸神经元在行为强化中扮演着复杂的角色。我们报道,VTA谷氨酸神经元或终末的光遗传刺激在操作行为分析中是一个积极的增强剂。与持续的VTA谷氨酸神经元刺激相比,小鼠表现出明显的偏好,导致行为反应与多巴胺神经元刺激显着不同,并对多巴胺受体拮抗剂产生抗药性。全细胞记录显示,刺激伏核或局部VTA侧支的VTA谷氨酸终末可诱发EPSCs;但在腹侧苍白球和外侧缰核可见兴奋性和单突触抑制电流,尽管各区域对突触后放电的净效应与观察到的奖赏行为效应一致。这些数据表明,VTA谷氨酸神经元以投射靶标依赖的方式共同释放GABA,它们的瞬时激活驱动阳性强化。腹侧被盖区(VTA)参与奖赏行为,但VTA谷氨酸能神经元在这一过程中的确切贡献尚不清楚。在这里,作者表明,对VTA谷氨酸能神经元的阶段性但不是持续的光遗传刺激是有回报的,涉及GABA的共同释放。
In addition to dopamine neurons, the ventral tegmental area (VTA) contains GABA-, glutamate- and co-releasing neurons, and recent reports suggest a complex role for the glutamate neurons in behavioural reinforcement. We report that optogenetic stimulation of VTA glutamate neurons or terminals serves as a positive reinforcer on operant behavioural assays. Mice display marked preference for brief over sustained VTA glutamate neuron stimulation resulting in behavioural responses that are notably distinct from dopamine neuron stimulation and resistant to dopamine receptor antagonists. Whole-cell recordings reveal EPSCs following stimulation of VTA glutamate terminals in the nucleus accumbens or local VTA collaterals; but reveal both excitatory and monosynaptic inhibitory currents in the ventral pallidum and lateral habenula, though the net effects on postsynaptic firing in each region are consistent with the observed rewarding behavioural effects. These data indicate that VTA glutamate neurons co-release GABA in a projection-target-dependent manner and that their transient activation drives positive reinforcement. Ventral tegmental area (VTA) is involved in reward behaviours, but the precise contribution of VTA glutamatergic neurons to this process is not known. Here the authors show that phasic but not sustained optogenetic stimulation of VTA glutamatergic neurons is rewarding and involves co-release of GABA.
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