Temporal scaling of dopamine neuron firing and dopamine release by distinct ion channels shape behavior.
Temporal scaling of dopamine neuron firing and dopamine release by distinct ion channels shape behavior.
复制标题
DOI：
10.1126/sciadv.adg8869
复制
发表时间：
2023-08-11
期刊：
影响因子：
13.6
通讯作者：
Zweifel, Larry S.
中科院分区：
文献类型：
--
作者：
Juarez, Barbara;Kong, Mi-Seon;Jo, Yong S.;Elum, Jordan E.;Yee, Joshua X.;Ng-Evans, Scott;Cline, Marcella;Hunker, Avery C.;Quinlan, Meagan A.;Baird, Madison A.;Elerding, Abigail J.;Johnson, Mia;Ban, Derek;Mendez, Adriana;Goodwin, Nastacia L.;Soden, Marta E.;Zweifel, Larry S.
多巴胺与强化学习有着广泛的联系，但多巴胺活动的模式是如何产生的还没有得到很好的解决。在这里，我们证明了两个离子通道，Kv4.3和BKCa1.1，调节多巴胺神经元放电和多巴胺释放的模式在不同的时间尺度上影响小鼠强化行为的不同阶段。在VTA多巴胺神经元中Kv4.3的失活增加了离体起搏器活性和兴奋性，这与在学习的工具范例中杠杆按压之前增加的体内放电率和斜坡动力学相关。Kv4.3的丧失增强了学习反应的表现并促进了消退。相比之下，BKCa1.1的损失增加爆发式放电和阶段性多巴胺释放，增强学习的工具性反应，并增强灭绝爆发杠杆按压在早期灭绝，这与加强和未加强的行动之间的活动变化更大。这些数据表明，中断的内在调节神经元活动的差异影响多巴胺动力学在强化和消退学习。中脑多巴胺神经元中的离子通道对于动作电位放电、多巴胺释放和学习的模式化至关重要。
Dopamine is broadly implicated in reinforcement learning, but how patterns of dopamine activity are generated is poorly resolved. Here, we demonstrate that two ion channels, Kv4.3 and BKCa1.1, regulate the pattern of dopamine neuron firing and dopamine release on different time scales to influence separate phases of reinforced behavior in mice. Inactivation of Kv4.3 in VTA dopamine neurons increases ex vivo pacemaker activity and excitability that is associated with increased in vivo firing rate and ramping dynamics before lever press in a learned instrumental paradigm. Loss of Kv4.3 enhances performance of the learned response and facilitates extinction. In contrast, loss of BKCa1.1 increases burst firing and phasic dopamine release that enhances learning of an instrumental response and enhances extinction burst lever pressing in early extinction that is associated with a greater change in activity between reinforced and unreinforced actions. These data demonstrate that disruption of intrinsic regulators of neuronal activity differentially affects dopamine dynamics during reinforcement and extinction learning. Ion channels in midbrain dopamine neurons are critical for patterning action potential firing, dopamine release, and learning.
登录
查看更多内容
影响因子：
5.5
作者：
JOHNSON, SW;NORTH, RA
通讯作者：
NORTH, RA
影响因子：
16.2
作者：
Gantz, Stephanie C.;Bean, Bruce P.
通讯作者：
Bean, Bruce P.
影响因子：
5.3
作者：
Niday, Zachary;Bean, Bruce P.
通讯作者：
Bean, Bruce P.
影响因子：
16.2
作者：
Jo YS;Heymann G;Zweifel LS
通讯作者：
Zweifel LS
DOI：
10.1523/jneurosci.2237-08.2008
发表时间：
2008-10-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Khaliq ZM;Bean BP
通讯作者：
Bean BP