Blockade of glutamatergic transmission in perirhinal cortex impairs object recognition memory in macaques

J Neurosci. 2015 Mar 25;35(12):5043-50. doi: 10.1523/JNEUROSCI.4307-14.2015.

Abstract

The perirhinal cortex (PRc) is essential for visual recognition memory, as shown by electrophysiological recordings and lesion studies in a variety of species. However, relatively little is known about the functional contributions of perirhinal subregions. Here we used a systematic mapping approach to identify the critical subregions of PRc through transient, focal blockade of glutamate receptors by intracerebral infusion of kynurenic acid. Nine macaques were tested for visual recognition memory using the delayed nonmatch-to-sample task. We found that inactivation of medial PRc (consisting of Area 35 together with the medial portion of Area 36), but not lateral PRc (the lateral portion of Area 36), resulted in a significant delay-dependent impairment. Significant impairment was observed with 30 and 60 s delays but not with 10 s delays. The magnitude of impairment fell within the range previously reported after PRc lesions. Furthermore, we identified a restricted area located within the most anterior part of medial PRc as critical for this effect. Moreover, we found that focal blockade of either NMDA receptors by the receptor-specific antagonist AP-7 or AMPA receptors by the receptor-specific antagonist NBQX was sufficient to disrupt object recognition memory. The present study expands the knowledge of the role of PRc in recognition memory by identifying a subregion within this area that is critical for this function. Our results also indicate that, like in the rodent, both NMDA and AMPA-mediated transmission contributes to object recognition memory.

Keywords: AP-7; NBQX; glutamate antagonist; kynurenate; medial temporal; pigtail macaque.

Publication types

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

MeSH terms

  • 2-Amino-5-phosphonovalerate / analogs & derivatives
  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Excitatory Amino Acid Antagonists / pharmacology
  • Kynurenic Acid / pharmacology
  • Macaca
  • Male
  • Quinoxalines / pharmacology
  • Receptors, AMPA / antagonists & inhibitors*
  • Receptors, AMPA / physiology
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Recognition, Psychology / drug effects
  • Recognition, Psychology / physiology*
  • Temporal Lobe / drug effects
  • Temporal Lobe / physiology*
  • Time Factors
  • Visual Perception / drug effects
  • Visual Perception / physiology

Substances

  • Excitatory Amino Acid Antagonists
  • Quinoxalines
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • 2-Amino-5-phosphonovalerate
  • Kynurenic Acid
  • 2-amino-7-phosphonoheptanoic acid