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

Grant support

This work was supported by the 973 Program (2011CBA00400, YS), the National Natural Science Foundation of China Project (31025012, YS), the Hundreds of Talents Program from Chinese Academy of Sciences, PICS-NavROLE (MM), and European Union FP7 Grant no. 602531 “DESIRE” (MM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.