Resonance properties of GABAergic interneurons in immature GAD67-GFP mouse neocortex

Abstract

Subthreshold resonance is a characteristic membrane property of different neuronal classes, is critically involved in the generation of network oscillations, and tunes the integration of synaptic inputs to particular frequency ranges. In order to investigate whether neocortical GABAergic interneurons show resonant behavior already during early postnatal development, we performed whole-cell patch-clamp recordings from visually identified interneurons in supragranular layers of parietal regions in coronal neocortical slices from postnatal day (P) P6–P13 GAD67-GFP knock-in mice. Subthreshold resonance was analyzed by injection of sinusoidal current with varying frequency. About 50% of the investigated GABAergic interneurons showed subthreshold resonance with an average frequency of 2.0±0.2Hz (n=38). Membrane hyperpolarization to –86mV attenuated the frequency and strength of subthreshold resonance. In the presence of 1mM Ni2+ subthreshold resonance was virtually abolished, suggesting that T-type Ca2+ currents are critically involved in the generation of resonance. In contrast, subthreshold resonance was not affected by ZD7288, a blocker of HCN channels. Application of TTX suppressed subthreshold resonance at depolarized, but not hyperpolarized membrane potential, suggesting that persistent Na+ current contribute to the amplification of membrane resonance. In summary, these results demonstrate that GABAergic interneurons express subthreshold resonance at low frequencies, with T-type Ca2+ and persistent Na+ currents underlying the generation of membrane resonance. The membrane resonance of immature interneurons may contribute to the generation of slow oscillatory activity pattern in the immature neocortex and enhance the temporal precision of synaptic integration in developing cortical neurons.