Cortical rhythms have been implicated in attention, exploratory and navigatory behavior, and in disease states such as schizophrenia, but their mechanisms remain vague. One clue to their origin is that neuronal gap junction expression is required for full power in the gamma band in the hippocampus. Gap junctions synchronize neighboring inhibitory interneurons of the same subtype but their role in network activity remains poorly understood. I propose to investigate the interactions between two gap-junction connected networks of interneurons, somatostatin-expressing interneurons and parvalbumin-expressing interneurons, and two types of cortical oscillations, theta (4-12 Hz) and gamma (30-80 Hz). I will investigate this link by selectively eliminating connexin36-based gap junctions in the two interneuronal networks and measuring the consequences on gamma and theta rhythms generated in vitro with whole-cell recordings and in vivo via electroencephalography and laminar electrode arrays.
Gap junctions have been associated with juvenile myoclonic epilepsy and with hallucinations induced by the anti-malarial drug mefloquine. The goal of the proposed study is to understand the role of neocortical gap junctions and in particular, how their expression affects cortical oscillations. It is likely that cortical oscillations are fundamentally important to the normal function of the cerebral cortex and abnormal oscillations may play a role in neurological disorders including schizophrenia.