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Dopamine D2 receptors regulate the action potential threshold by modulating T-type calcium channels in stellate cells of the medial entorhinal cortex.

Xueqin JinQian ChenYan SongJie ZhengKuo XiaoShan ShaoZibing FuMing YiYang YangZhuo Huang
Published in: The Journal of physiology (2019)
Stellate cells in the medial entorhinal cortex (MEC) are considered to constitute the largest population of grid cells, which provide spatial representation to support animal estimation of location. Although dopaminergic fibres from the ventral tegmental area and substantia nigra pars compacta innervate the majority of the cortex, including the MEC, little is known about how dopamine modulates the function of MEC stellate cells. Because dopamine D2 receptors (D2Rs) are involved in spatial cognition and MEC contains high levels of D2Rs, we investigated how D2R activation modulates the neuronal intrinsic excitability of stellate cells. Electrophysiological recordings, optogenetics and molecular biology experiments were performed to investigate the mechanism in mice. Activation of axonal D2Rs, not dendritic or somatic D2Rs, elevated the action potential (AP) threshold and decreased the intrinsic excitability of stellate cells, which was caused by shifting rightward the activation properties of T-type Ca2+ channels in a D2R-protein kinase A-dependent manner without affecting their steady-state inactivation curve. In support, immunofluorescence assays revealed colocalization of D2Rs and Cav 3.2 calcium channels within the axon initial segment. These findings are likely to have significant implications for understanding the cellular processes by which dopamine influences neuronal excitability and they may also be applicable to other hippocampal and cortical regions as dopaminergic fibres innervate wide brain regions. Taken together, these findings provide a novel cellular mechanism by which D2Rs modulate AP threshold of stellate cells through T-type Ca2+ channels in MEC, indicating that D2Rs of MEC play a vital role in modulating the information processing of stellate cells.
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