Combined optogenetic and pharmacological analysis of 5-HT control of cortical microcircuitry

认知的细胞基础存在于由兴奋性神经元和抑制性神经元组成的复杂的皮层微回路中。复杂的兴奋-抑制平衡允许同步的神经元活动产生不同频率的神经网络振荡。它们通过允许本地和远程神经回路中的有效通信来编码行为。Pv+中间神经元是一类主要的抑制性神经元，对锥体神经元有很强的抑制作用，在产生高频伽马(30-80 Hz)振荡中起着关键作用。大脑皮层伽马振荡在处理感觉信息和执行功能的过程中增加了能量，被认为是正常认知的关键。神经递质5-羟色胺(5-羟色胺；5-羟色胺)调节失调被广泛认为与认知功能障碍有关。新的证据表明，5-羟色胺调节可能的PV+神经元的电活动，并调节伽马振荡。拟议的项目将使用现代遗传工具和药理学分析来表征5-羟色胺和PV+中间神经元之间的相互作用，从而建立支撑认知功能的关键细胞机制。WCUB，ENWW

The cellular basis of cognition lies within cortical microcircuits which comprise complex ensembles of excitatory and inhibitory neurons. The intricate excitatory-inhibitory balance allows synchronised neuronal activity to generate neural network oscillations of different frequencies. These encode behaviour by allowing efficient communication in local and distant neural circuits. Parvalbuminexpressing (PV+) interneurons , a major class of inhibitory neurons, powerfully inhibit pyramidal neurons and play a critical role in generating high frequency gamma (30-80 Hz) oscillations. Cortical gamma oscillations increase in power during the processing of sensory information and executive functions, and are considered crucial for normal cognition. Dysregulation of the neurotransmitter 5-hydroxytryptamine (5-HT; serotonin) is widely implicated in cognitive dysfunction. Emerging evidence suggests that 5-HT modulates the electrical activity of putative PV+ neurons and modulates gamma oscillations. The proposed project will use modern genetic tools and pharmacological analysis to characterise the interaction between 5-HT and PV+ interneurons, and thereby establish key cellular mechanisms underpinning cognitive function. WCUB, ENWW