GABAergic interneurons and the development of network oscillations

Abstract

Event Abstract Back to Event GABAergic interneurons and the development of network oscillations Thomas Voigt1* 1 Otto-von-Guericke University, Institute of Physiology, Germany Neocortical neurons dissociated from embryonic tissue and grown in a standardized environment form synaptically interconnected and electrically active networks. Depending on the age of dissociation, the major developmental steps (cell proliferation, cell migration, generation of different cell types, synaptogenesis and emergence of spontaneous activity) occur in the culture dish within a schedule comparable to the development in the intact cortex. With certain preparation and cultivation techniques raising neuronal networks with defined cellular content is possible. Our cell culture experiments reveal a close interdependence between functional network development and the maturation of GABAergic neurons and synapses. GABAergic interneurons with large axonal arbors advance the initiation of large scale synchronous network activity, which is similar to the cortical early network oscillations (cENOs) observed in cortical slices 1-3. The emergent network activity in turn promotes growth and axonal maturation of the pioneer GABAergic neurons, a process modulated by thyroid hormones 4. Early synchronous network activity also supports the activation of immature glutamatergic synapses but restrains the formation of long range axonal connections 5. Specially the integration of late-born GABAergic interneurons depends on the developing network activity, which promotes their survival and limits their migration 6,7. Apart from the initiation of the early network activity, GABAergic signaling contributes to the regression and decorrelation of early oscillations 8. This developmental process is promoted by the expression of the potassium-chloride transporter KCC2 and the gradual change of the chloride equilibrium potential, which shifts GABA action from depolarizing to hyperpolarizing. The decorrelation of network activity requires the presence of GABAergic interneurons and can be induced by blocking the sodium-potassium-chloride transporter NKCC1 with bumetanide.