Monitoring and controlling ion dynamics in parvalbumin-expressing interneuronsduring epileptiform activity. (360G-Wellcome-102364_Z_13_A)

The disrupted interplay between excitation and inhibition within neuronal networks has long been implicated in seizure pathophysiology. Pharmacological blockade of synaptic inhibition promotes epileptic activity and when inhibitory restraint upon network activity fails, spatially clustered excitatory pyramidal neurons are recruited to epileptiform events. A key challenge is to understand how different populations of inhibitory interneurons contribute to these processes. Recent research has suggested thatparvalbumin expressing (PV+) interneurons play a central role in setting inhibitory restraint within neuronal networks, but the underlying mechanisms remain poorly understood and how the different properties of interneuron populations influence seizure dynamics is not clear. The efficacy of synaptic inhibition is determined partly by the regulation of intracellular chloride levels, as well as how inhibitory interneurons are recruited and their activity is maintained. This project focuses on the role of PV+ interneurons in these processes. The goals are to investigate activity-dependent changes in intracellular chloride levels in PV+ interneurons and to examine the cellular mechanisms that limit inhibitory restraint provided by PV+ interneurons. Thesequestions will be addressed using in vitro and in vivo animal models of focal epilepsy.