Action potential initiation in neocortical inhibitory interneurons

PLoS Biol. 2014 Sep 9;12(9):e1001944. doi: 10.1371/journal.pbio.1001944. eCollection 2014 Sep.

Abstract

Action potential (AP) generation in inhibitory interneurons is critical for cortical excitation-inhibition balance and information processing. However, it remains unclear what determines AP initiation in different interneurons. We focused on two predominant interneuron types in neocortex: parvalbumin (PV)- and somatostatin (SST)-expressing neurons. Patch-clamp recording from mouse prefrontal cortical slices showed that axonal but not somatic Na+ channels exhibit different voltage-dependent properties. The minimal activation voltage of axonal channels in SST was substantially higher (∼7 mV) than in PV cells, consistent with differences in AP thresholds. A more mixed distribution of high- and low-threshold channel subtypes at the axon initial segment (AIS) of SST cells may lead to these differences. Surprisingly, NaV1.2 was found accumulated at AIS of SST but not PV cells; reducing NaV1.2-mediated currents in interneurons promoted recurrent network activity. Together, our results reveal the molecular identity of axonal Na+ channels in interneurons and their contribution to AP generation and regulation of network activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Axons / metabolism
  • Gene Expression
  • Interneurons / cytology
  • Interneurons / metabolism*
  • Mice
  • Mice, Transgenic
  • Microtomy
  • NAV1.2 Voltage-Gated Sodium Channel / genetics
  • NAV1.2 Voltage-Gated Sodium Channel / metabolism
  • Neocortex / cytology
  • Neocortex / physiology*
  • Nerve Net / cytology
  • Nerve Net / physiology*
  • Parvalbumins / genetics
  • Parvalbumins / metabolism
  • Patch-Clamp Techniques
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / physiology*
  • Somatostatin / genetics
  • Somatostatin / metabolism
  • Tissue Culture Techniques

Substances

  • NAV1.2 Voltage-Gated Sodium Channel
  • Parvalbumins
  • Somatostatin