Epilepsy – Pharmacological Modulation of Gap-Junction Signaling and Neuronal Synchrony

Technology overview

The mammalian brain contains two types of synapses: chemical and electrical. The overwhelming majority of research on neuronal communication has focused on chemical synaptic transmission, particularly in mammalian systems. By contrast, only recently has the importance of electrical synapses, or gap junctions, been appreciated.

Although a large percentage of neurological and neuropsychiatric diseases involve imbalances of excitation and inhibition, treatments of these diseases have completely neglected gap junctional synapses, a key component of inhibitory circuitry. As a source of synchronization of inhibitory neurons, neuronal gap junctions are crucial to disorders of inhibition, especially epilepsy. And despite the prevalence of these coupled networks of interneurons, the properties and functional consequences of gap junctions in the mammalian CNS are poorly understood.

Drs. Carole Landisman and Philippe Coulon are studying the modulation of gap-junction synchrony by gap junctional plasticity, which may provide powerful insights into how regulation — and dysregulation — of gap junctions can change their function within neuronal circuits. Their research uses paired whole-cell recordings in rodent brain slices and imaging of neuronal network activity using activity-sensitive dyes to investigate differential interactions of pharmacological agents with gap junction signaling and neuronal synchrony. In addition, the research addresses how this pharmacologically-induced modulation can differentially change the local activation patterns of gap junction-coupled networks, depending on the network state — tonic or burst firing. It is expected that this research will inform novel and sophisticated interventions in diseases that involve disorders of inhibition.

Comments are closed.