Regulation of interneuron excitability by gap junction coupling with principal cells

Nat Neurosci. 2013 Dec;16(12):1764-72. doi: 10.1038/nn.3569. Epub 2013 Nov 3.

Abstract

Electrical coupling of inhibitory interneurons can synchronize activity across multiple neurons, thereby enhancing the reliability of inhibition onto principal cell targets. It is unclear whether downstream activity in principal cells controls the excitability of such inhibitory networks. Using paired patch-clamp recordings, we show that excitatory projection neurons (fusiform cells) and inhibitory stellate interneurons of the dorsal cochlear nucleus form an electrically coupled network through gap junctions containing connexin36 (Cxc36, also called Gjd2). Remarkably, stellate cells were more strongly coupled to fusiform cells than to other stellate cells. This heterologous coupling was functionally asymmetric, biasing electrical transmission from the principal cell to the interneuron. Optogenetically activated populations of fusiform cells reliably enhanced interneuron excitability and generated GABAergic inhibition onto the postsynaptic targets of stellate cells, whereas deep afterhyperpolarizations following fusiform cell spike trains potently inhibited stellate cells over several hundred milliseconds. Thus, the excitability of an interneuron network is bidirectionally controlled by distinct epochs of activity in principal cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Animals, Newborn
  • Biophysical Phenomena / drug effects
  • Biophysical Phenomena / genetics
  • Channelrhodopsins
  • Cochlear Nucleus / cytology
  • Connexins / deficiency
  • Connexins / genetics
  • Evoked Potentials, Auditory, Brain Stem / drug effects
  • Evoked Potentials, Auditory, Brain Stem / genetics
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Female
  • Gap Junctions / drug effects
  • Gap Junctions / physiology*
  • In Vitro Techniques
  • Interneurons / drug effects
  • Interneurons / physiology*
  • Luminescent Proteins / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Net / drug effects
  • Nerve Net / physiology*
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neurons / classification
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurotransmitter Agents / pharmacology
  • Vesicular Glutamate Transport Protein 2 / genetics

Substances

  • Channelrhodopsins
  • Connexins
  • Luminescent Proteins
  • Neurotransmitter Agents
  • Vesicular Glutamate Transport Protein 2
  • connexin 36