Inhibitory GABA action in the neonatal mouse cortex in vivo
We present a novel optogenetic approach for the investigation of excitatory and inhibitory GABA actions in cortical neuronal networks using a mouse knock-in line with conditional expression of channelrhodopsin-2 (ChR2) in GABAergic interneurons. During whole-cell recordings from hippocampal and neocortical slices from postnatal day P2-15 mice, photostimulation caused depolarization and excitation of interneurons and evoked barrages of postsynaptic GABAergic currents. Excitatory/inhibitory GABA actions on pyramidal cells were assessed by monitoring the alteration in the frequency of excitatory postsynaptic currents (EPSCs) during photostimulation of interneurons. We found that in slices from P2-8 mice, photostimulation evoked an increase in EPSC frequency whereas in P9-15 mice, the response switched to a reduction in EPSC frequency indicating a developmental excitatory-to-inhibitory switch in GABA actions on glutamatergic neurons. Using a similar approach in urethane-anaesthetized animals in vivo, we found that photostimulation of interneurons reduces EPSC frequency at ages P3-9. Thus, expression of ChR2 in GABAergic interneurons of mice enables selective photostimulation of interneurons during the early postnatal period, and these mice display a developmental excitatory-to-inhibitory switch in GABA action in cortical slices in vitro, but so far show mainly inhibitory GABA actions on spontaneous EPSCs in the immature hippocampus and neocortex in vivo.