Activity-Dependent Ectopic Spiking in Parvalbumin-Expressing Interneurons of the Neocortex

Abstract

Canonically, action potentials of most mammalian neurons initiate at the axon initial segment and propagate bidirectionally: orthodromically along the distal axon, and retrogradely into the soma and dendrites. Under some circumstances action potentials may initiate ectopically, at sites distal to the axon initial segment, and propagate antidromically along the axon. These ectopic action potentials (EAPs) have been observed in experimental models of seizures and chronic pain, and more rarely in nonpathological forebrain neurons. Here we report that a large majority of parvalbumin-expressing (PV+) interneurons in upper layers of mouse neocortex, from both orbitofrontal and primary somatosensory areas, fire EAPs after sufficient activation of their somata. Somatostatin-expressing interneurons also fire EAPs, though less robustly. Ectopic firing in PV+ cells occurs in varying temporal patterns and can persist for several seconds. PV+ cells evoke strong synaptic inhibition in pyramidal neurons and interneurons and play critical roles in cortical function. Our results suggest that ectopic spiking of PV+ interneurons is common, and may contribute to both normal and pathological network functions of the neocortex. SIGNIFICANCE STATEMENTA form of neuronal firing that emerges in distal axons and terminals - the ectopic action potential (EAP) - has been detected in a few cell populations of the cerebral cortex. Previous investigations of parvalbumin-positive interneurons in neocortex had suggested only a small percentage of cells can fire EAPs. We found that a large fraction of parvalbumin-positive interneurons in the superficial layers of neocortex, including first-order and higher-order areas, can fire EAPs. These results broaden our understanding of the intrinsic firing characteristics of these critically important inhibitory interneurons.