Roles of GABAergic interneurons in calcium waves of the developing neocortex

Abstract

Between early periods of brain development when genetic programs structure the basic features of the brain, and later periods when sensory-driven electrical activity refines neuronal connections, spontaneous activity generated by immature neurons plays a critical role in their development. In these studies we examine population activity in the developing neocortex: waves of action potentials propagating across the entirety of the cortex that may be measured with extracellular electrodes or optical techniques that measure cellular calcium influxes associated with waves. Using pharmacological and genetic blockade of neurotransmitter signaling we show complex roles for the neurotransmitter GABA in generating and regulating wave activity, as it may act almost simultaneously as an excitatory neurotransmitter in generating wave activity and also an inhibitory neurotransmitter that dampens the electrical oscillations of waves. Finally we use genetic expression of fluorescent proteins to label the GABA producing cells of the brain, inhibitory interneurons. We measure calcium activity in these cells and show that they express multiple types of calcium signals that may regulate different stages of cellular development.