Loss of mGluR-mediated hyperpolarizations and increase in mGluR depolarizations in basolateral amygdala neurons in kindling-induced epilepsy

J Neurophysiol. 1996 Oct;76(4):2808-12. doi: 10.1152/jn.1996.76.4.2808.

Abstract

1. Intracellular recordings were made from neurons of the basolateral amygdala (BLA) in in vitro slice preparations to determine long-term differences in metabotropic glutamate receptor (mGluR) agonist-induced membrane responses in control and amygdala-kindled rats. 2. (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine-1 (L-CCG-I; 100 microM) typically evoked a hyperpolarization/outward current in control BLA neurons; the hyperpolarization is mediated through a group-II-like mGluR subtype of receptor and is recorded in accommodating neurons that cease firing in the presence of a long (400 ms) depolarizing current injection (0.5 nA). In amygdala-kindled slices, L-CCG-I (100 microM) hyperpolarized only 1 of 13 BLA neurons. 3. 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) (100 microM) elicited a hyperpolarization/depolarization (outward/inward current) in control neurons and evoked only a membrane depolarization (inward current) in kindled BLA neurons; this depolarization is similar to that mediated by group I mGluR activation in other neurons. 4. In control nonaccommodating neurons the concentration-response relationship for the 1S,3R-ACPD-induced inward current had a median effective concentration (EC50) of 49 microM and a maximum amplitude of 182 +/- 30 (mean +/- SE) pA. In kindled nonaccommodating neurons the EC50 of the concentration-response relationship for 1S,3R-ACPD was shifted to 29 microM and the maximum value increased to 265 +/- 15 pA, reflecting an increase in efficacy. 5. These data suggest that amygdala kindling causes lasting changes in mGluR responses in the BLA reflecting a downregulation of a group-II-like mGluR subtype mediating the hyperpolarizing response and an upregulation of a group I mGluR1 or 5 subtype. The hyperpolarizing response reduced by kindling and the increase in the group I mGluR response may reflect an alteration in the balance between inhibition and excitation and may contribute to the transition to epileptiform bursting in kindled neurons.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amygdala / cytology
  • Amygdala / drug effects
  • Amygdala / physiology*
  • Animals
  • Cycloleucine / analogs & derivatives*
  • Cycloleucine / pharmacology
  • Electric Conductivity
  • Epilepsy / pathology
  • Epilepsy / physiopathology*
  • Evoked Potentials / drug effects
  • In Vitro Techniques
  • Kindling, Neurologic*
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurons / drug effects
  • Neurons / physiology*
  • Potassium Channels / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / physiology*

Substances

  • Potassium Channels
  • Receptors, Metabotropic Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane