Synchronized gamma-frequency inhibition in neocortex depends on excitatory-inhibitory interactions but not electrical synapses

J Neurophysiol. 2016 Aug 1;116(2):351-68. doi: 10.1152/jn.00071.2016. Epub 2016 Apr 27.


Synaptic inhibition plays a crucial role in the precise timing of spiking activity in the cerebral cortex. Synchronized, rhythmic inhibitory activity in the gamma (30-80 Hz) range is thought to be especially important for the active, information-processing neocortex, but the circuit mechanisms that give rise to synchronized inhibition are uncertain. In particular, the relative contributions of reciprocal inhibitory connections, excitatory-inhibitory interactions, and electrical synapses to precise spike synchrony among inhibitory interneurons are not well understood. Here we describe experiments on mouse barrel cortex in vitro as it spontaneously generates slow (<1 Hz) oscillations (Up and Down states). During Up states, inhibitory postsynaptic currents (IPSCs) are generated at gamma frequencies and are more synchronized than excitatory postsynaptic currents (EPSCs) among neighboring pyramidal cells. Furthermore, spikes in homotypic pairs of interneurons are more synchronized than in pairs of pyramidal cells. Comparing connexin36 knockout and wild-type animals, we found that electrical synapses make a minimal contribution to synchronized inhibition during Up states. Estimations of the delays between EPSCs and IPSCs in single pyramidal cells showed that excitation often preceded inhibition by a few milliseconds. Finally, tonic optogenetic activation of different interneuron subtypes in the absence of excitation led to only weak synchrony of IPSCs in pairs of pyramidal neurons. Our results suggest that phasic excitatory inputs are indispensable for synchronized spiking in inhibitory interneurons during Up states and that electrical synapses play a minimal role.

Keywords: cortex; electrical synapse; gamma; inhibition; oscillation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / genetics
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Channelrhodopsins
  • Connexins / deficiency
  • Connexins / genetics
  • Excitatory Amino Acid Antagonists / pharmacology
  • Gamma Rhythm / drug effects
  • Gamma Rhythm / genetics
  • Gamma Rhythm / physiology*
  • Interneurons / drug effects
  • Interneurons / physiology*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Neurological
  • Neocortex / cytology
  • Neocortex / physiology*
  • Neural Inhibition / drug effects
  • Parvalbumins / genetics
  • Parvalbumins / metabolism
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology*
  • Quinoxalines / pharmacology
  • Somatostatin / genetics
  • Somatostatin / metabolism
  • Synapses / classification
  • Synapses / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Valine / analogs & derivatives
  • Valine / pharmacology


  • Bacterial Proteins
  • Channelrhodopsins
  • Connexins
  • Excitatory Amino Acid Antagonists
  • Luminescent Proteins
  • Parvalbumins
  • Quinoxalines
  • connexin 36
  • yellow fluorescent protein, Bacteria
  • Somatostatin
  • FG 9041
  • 2-amino-5-phosphopentanoic acid
  • Valine