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

Neocortical Layer 1 (L1) consists of 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: Canopy cells show an irregular firing pattern near rheobase; Neurogliaform cells (NGFCs) are late-spiking, and their firing rate accelerates during current injections; cells with strong expression of the α7 nicotinic receptor (α7 cells), display initial (rebound) bursting; vasoactive intestinal peptide (VIP) expressing cells exhibit high input resistance, strong adaptation, and irregular firing. Computational modelling revealed that these neurophysiological diverse features could be explained by an extended exponential-integrate-and-fire neuron model with varying contributions of a slowly inactivating K+ channel (SIK), a T-type Ca2+ channel, and a spike-triggered Ca2+-dependent K+ 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 due to the interaction between strong adaptation and a SIK channel. The reported findings of single neuron dynamics should be incorporated to elucidate how different L1 cell types contribute to the integration of top-down signaling and local processes.