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

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