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

认知的细胞基础存在于皮层微回路中，其中包括兴奋性和抑制性神经元的复杂集合。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。这些编码的行为，允许有效的沟通，在本地和远程神经回路。表达小白蛋白（PV+）的中间神经元是抑制性神经元的主要类别，其有力地抑制锥体神经元并且在产生高频γ（30-80 Hz）振荡中起关键作用。皮质伽马振荡在感觉信息和执行功能的处理过程中增加功率，并且被认为对正常认知至关重要。神经递质5-羟色胺（5-HT; 5-羟色胺）的调节异常广泛涉及认知功能障碍。新出现的证据表明，5-HT调制推定PV+神经元的电活动和调制γ振荡。该项目将使用现代遗传工具和药理学分析来验证5-HT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