Contribution of Ionotropic Glutamatergic Receptors to Excitability and Attentional Signals in Macaque Frontal Eye Field

Cereb Cortex. 2021 Jun 10;31(7):3266-3284. doi: 10.1093/cercor/bhab007.

Abstract

Top-down attention, controlled by frontal cortical areas, is a key component of cognitive operations. How different neurotransmitters and neuromodulators flexibly change the cellular and network interactions with attention demands remains poorly understood. While acetylcholine and dopamine are critically involved, glutamatergic receptors have been proposed to play important roles. To understand their contribution to attentional signals, we investigated how ionotropic glutamatergic receptors in the frontal eye field (FEF) of male macaques contribute to neuronal excitability and attentional control signals in different cell types. Broad-spiking and narrow-spiking cells both required N-methyl-D-aspartic acid and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation for normal excitability, thereby affecting ongoing or stimulus-driven activity. However, attentional control signals were not dependent on either glutamatergic receptor type in broad- or narrow-spiking cells. A further subdivision of cell types into different functional types using cluster-analysis based on spike waveforms and spiking characteristics did not change the conclusions. This can be explained by a model where local blockade of specific ionotropic receptors is compensated by cell embedding in large-scale networks. It sets the glutamatergic system apart from the cholinergic system in FEF and demonstrates that a reduction in excitability is not sufficient to induce a reduction in attentional control signals.

Keywords: attention; frontal cortex; neuropharmacology; primate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Attention / drug effects
  • Attention / physiology*
  • Excitatory Amino Acid Agonists / pharmacology*
  • Frontal Lobe / drug effects
  • Frontal Lobe / physiology*
  • Macaca mulatta
  • Male
  • N-Methylaspartate / pharmacology
  • Photic Stimulation / methods*
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Receptors, AMPA / agonists
  • Receptors, AMPA / physiology*
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Saccades / drug effects
  • Saccades / physiology
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology

Substances

  • Excitatory Amino Acid Agonists
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • N-Methylaspartate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid