Mechanisms of Dominant Electrophysiological Features of Four Subtypes of Layer 1 Interneurons

Neocortical layer 1 (L1) consists of the distal dendrites of pyramidal cells and GABAergic interneurons (INs) and receives extensive long-range “top-down” projections, but L1 INs remain poorly understood. In this work, we systematically examined the distinct dominant electrophysiological features for four unique IN subtypes in L1 that were previously identified from mice of either gender: Canopy cells show an irregular firing pattern near rheobase; neurogliaform cells are late-spiking, and their firing rate accelerates during current injections; cells with strong expression of the a7 nicotinic receptor (a7 cells), display onset (rebound) bursting; vasoactive intestinal peptide (VIP) expressing cells exhibit high input resistance, strong adaptation, and irregular firing. Computational modeling revealed that these diverse neurophysiological features could be explained by an extended exponential-integrate-and-fire neuron model with varying contributions of a slowly inactivating K¹ channel, a T-type Ca²¹ channel, and a spike-triggered Ca²¹-dependent K¹ channel. In particular, we show that irregular firing results from square-wave bursting through a fast-slow analysis. Furthermore, we demonstrate that irregular firing is frequently observed in VIP cells because of the interaction between strong adaptation and a slowly inactivating K¹ channel. At last, we reveal that the VIP and a7 cell models resonant with alpha/theta band input through a dynamic gain analysis.