Ionic mechanisms underlying repetitive high-frequency burst firing in supragranular cortical neurons

Neocortical neurons in awake, behaving animals can generate high-frequency (>300 Hz) bursts of action potentials, either in single bursts or in a repe titive manner. Intracellular recordings of layer II/III pyramidal neurons w ere obtained from adult ferret visual cortical slices maintained in vitro t o investigate the ionic mechanisms by which a subgroup of these cells gener ates repetitive, high-frequency burst discharges, a pattern referred to as "chattering." The generation of each but the first action potential in a bu rst was dependent on the critical interplay between the afterhyperpolarizat ions (AHPs) and afterdepolarizations (ADPs) that followed each action poten tial. The spike-afterdepolarization and the generation of action potential bursts were dependent on Na+, but not Ca2+, currents. Neither blocking of t he transmembrane flow of Ca2+ nor the intracellular chelation of free Ca2with BAPTA inhibited the generation of intrinsic bursts. In contrast, decre asing the extracellular Na+ concentration or pharmacologically blocking Na currents with tetrodotoxin, QX-314, or phenytoin inhibited bursting before inhibiting action potential generation. Additionally, a subset of layer II /III pyramidal neurons could be induced to switch from repetitive single sp iking to a burst-firing mode by constant depolarizing current injection, by raising extracellular K+ concentrations, or by potentiation of the persist ent Na+ current with the Na+ channel toxin ATX II. These results indicate t hat cortical neurons may dynamically regulate their pattern of action poten tial generation through control of Na+ and K+ currents. The generation of h igh-frequency burst discharges may strongly influence the response of posts ynaptic neurons and the operation of local cortical networks.