Functional properties of GABA synaptic inputs onto GABA neurons in monkey prefrontal cortex

J Neurophysiol. 2015 Mar 15;113(6):1850-61. doi: 10.1152/jn.00799.2014. Epub 2014 Dec 24.

Abstract

In rodent cortex GABAA receptor (GABAAR)-mediated synapses are a significant source of input onto GABA neurons, and the properties of these inputs vary among GABA neuron subtypes that differ in molecular markers and firing patterns. Some features of cortical interneurons are different between rodents and primates, but it is not known whether inhibition of GABA neurons is prominent in the primate cortex and, if so, whether these inputs show heterogeneity across GABA neuron subtypes. We thus studied GABAAR-mediated miniature synaptic events in GABAergic interneurons in layer 3 of monkey dorsolateral prefrontal cortex (DLPFC). Interneurons were identified on the basis of their firing pattern as fast spiking (FS), regular spiking (RS), burst spiking (BS), or irregular spiking (IS). Miniature synaptic events were common in all of the recorded interneurons, and the frequency of these events was highest in FS neurons. The amplitude and kinetics of miniature inhibitory postsynaptic potentials (mIPSPs) also differed between DLPFC interneuron subtypes in a manner correlated with their input resistance and membrane time constant. FS neurons had the fastest mIPSP decay times and the strongest effects of the GABAAR modulator zolpidem, suggesting that the distinctive properties of inhibitory synaptic inputs onto FS cells are in part conferred by GABAARs containing α1 subunits. Moreover, mIPSCs differed between FS and RS interneurons in a manner consistent with the mIPSP findings. These results show that in the monkey DLPFC GABAAR-mediated synaptic inputs are prominent in layer 3 interneurons and may differentially regulate the activity of different interneuron subtypes.

Keywords: GABAA receptor; disinhibition; dorsolateral prefrontal cortex; inhibitory postsynaptic potential; interneuron; primate.

Publication types

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

MeSH terms

  • Action Potentials*
  • Animals
  • Female
  • GABA-A Receptor Agonists / pharmacology
  • GABAergic Neurons / drug effects
  • GABAergic Neurons / metabolism*
  • GABAergic Neurons / physiology
  • Inhibitory Postsynaptic Potentials
  • Interneurons / drug effects
  • Interneurons / metabolism
  • Interneurons / physiology
  • Macaca mulatta
  • Male
  • Miniature Postsynaptic Potentials
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / physiology
  • Pyridines / pharmacology
  • Synapses / drug effects
  • Synapses / metabolism*
  • Synapses / physiology
  • Zolpidem
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • GABA-A Receptor Agonists
  • Pyridines
  • gamma-Aminobutyric Acid
  • Zolpidem