Activity-dependent ectopic action potentials in regular-spiking neurons of the neocortex

Area of Science:

• Neuroscience
• Cellular Neuroscience
• Computational Neuroscience

Background:

• Action potentials typically propagate orthodromically along neuronal axons.
• Ectopic action potentials (EAPs) are action potentials that travel antidromically, initiated at atypical sites.
• While observed in pathological conditions and some interneurons, EAPs have not been reported in pyramidal neurons under nonpathological conditions.

Purpose of the Study:

• To investigate the potential for ectopic action potential generation in non-pathological pyramidal neurons.
• To characterize the conditions under which pyramidal neurons exhibit ectopic firing.

Main Methods:

• Whole-cell patch clamp recordings were performed on mouse neocortical pyramidal neurons in vitro.
• Ectopic action potentials were elicited by triggering orthodromic action potentials using various current step protocols and pulse trains (30-100 Hz).

Main Results:

• A significant proportion (72.7%) of regular-spiking (RS) pyramidal neurons could fire EAPs following specific stimuli.
• Most RS neurons (56.1%) exhibited EAP firing across a range of stimulus conditions.
• Ectopic firing initiation required a substantial number of preceding orthodromic action potentials (average ~864 over ~81 seconds).
• Some neurons showed frequency-tuned responses, suggesting selective stimulus processing.

Conclusions:

• Pyramidal neurons can integrate information over extended periods, leading to self-generated firing originating in distal axons.
• The widespread capacity for EAP generation in RS cells suggests potential roles in neural information processing, cortical oscillations, and seizure susceptibility.