经典瞬时受体电位通道（TRPC）是正常脑功能和神经精神疾病的重要调控因子，其中TRPC4在大脑广泛表达，尤其在情绪调控脑区——外侧隔核有非常高的表达。TRPC4基因敲除小鼠表现出恐惧缺失和抗焦虑行为。我们的前期研究也发现抑制TRPC4能减轻小鼠应激引起的焦虑和抑郁。然而，TRPC4调控负性情绪的神经机制尚不清楚。本项目拟首先利用病毒示踪和免疫荧光染色首先确定外侧隔核中TRPC4神经元的类型及投射的目标脑区；而后以TRPC4基因敲除鼠为对照，采用脑片膜片钳探索在给予特殊的TRPC4神经元抑制剂之后，外侧隔核的神经电生理活动特征；最后在行为的水平上，验证在外侧隔核抑制TRPC4神经元之后，动物情绪行为的变化与神经元活动的相关性。通过上述研究，我们将明确外侧隔TRPC4神经元的分布类型及其对负性情绪调控的神经原理，也为情绪障碍的新型药物研发提供理论基础。

Transient receptor potential canonical (TRPC) channels are widely expressed in brain and involved in various aspects of normal brain function and neuropsychiatric disorders. TRPC4 has much higher distribution level in brain, espetially in emotional regulation center- lateral septum. The TRPC4 knockout mice exhibits defects in internal fear and anxiolytic effect. Our previous study also found that the inhibitior of TRPC4 presents antidepressant and anti-anxiety effects. However, the neural mechanism of TRPC4 on the emotional regulaton was still unclear. In this project, we will use viral neuronal tracing and immunofluorescence staining to clarify the amount and type of TRPC4 neurons in later septum and its targeted projection area; then using TRPC4 knockout mice as negtive control, we will explore the neural electrophysiological characteristics of TRPC4 involved neurocircuit by pharmacological inhibition of TRPC4. The relationship between TRPC4 neurons inhibition and behavioral consequence will further be investigated. This study will clarify the distribution and type of TRPC4 neuron, help us better understand how TRPC4 neurons regulate anxiety emotion, and support theoretical base for developing new drugs in mood disorders.