Differential Contribution of Kainate Receptors to Excitatory Postsynaptic Currents in Superficial Layer Neurons of the Rat Medial Entorhinal Cortex

Neuroscience. 2007 May 25;146(3):1000-12. doi: 10.1016/j.neuroscience.2007.02.035. Epub 2007 Mar 29.

Abstract

Although in situ hybridization studies have revealed the presence of kainate receptor (KAR) mRNA in neurons of the rat medial entorhinal cortex (mEC), the functional presence and roles of these receptors are only beginning to be examined. To address this deficiency, whole cell voltage clamp recordings of locally evoked excitatory postsynaptic currents (EPSCs) were made from mEC layer II and III neurons in combined entorhinal cortex-hippocampal brain slices. Three types of neurons were identified by their electroresponsive membrane properties, locations, and morphologies: stellate-like "Sag" neurons in layer II (S), pyramidal-like "No Sag" neurons in layer III (NS), and "Intermediate Sag" neurons with varied morphologies and locations (IS). Non-NMDA EPSCs in these neurons were composed of two components, and the slow decay component in NS neurons had larger amplitudes and contributed more to the combined EPSC than did those observed in S and IS neurons. This slow component was mediated by KARs and was characterized by its resistance to either 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466, 100 microM) or 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[lsqb]f[rsqb]quinoxaline-7-sulfonamide (NBQX, 1 microM), relatively slow decay kinetics, and sensitivity to 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10-50 microM). KAR-mediated EPSCs in pyramidal-like NS neurons contributed significantly more to the combined non-NMDA EPSC than did those from S and IS neurons. Layer III neurons of the mEC are selectively susceptible to degeneration in human temporal lobe epilepsy (TLE) and animal models of TLE such as kainate-induced status epilepticus. Characterizing differences in the complement of postsynaptic receptors expressed in injury prone versus injury resistant mEC neurons represents an important step toward understanding the vulnerability of layer III neurons seen in TLE.

Publication types

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

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Benzodiazepines / pharmacology
  • Cell Death / physiology
  • Electrophysiology
  • Entorhinal Cortex / cytology*
  • Entorhinal Cortex / physiology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / physiology*
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • In Vitro Techniques
  • Lysine / analogs & derivatives
  • Lysine / pharmacology
  • Male
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Pyramidal Cells / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Kainic Acid / physiology*

Substances

  • Excitatory Amino Acid Antagonists
  • Receptors, Kainic Acid
  • GYKI 52466
  • Benzodiazepines
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • biocytin
  • Lysine