Kindling-induced asymmetric accumulation of hippocampal 7S SNARE complexes correlates with enhanced glutamate release

Epilepsia. 2012 Jan;53(1):157-67. doi: 10.1111/j.1528-1167.2011.03345.x. Epub 2011 Dec 9.


Purpose: To correlate kindling-associated alterations of the neurotransmitter secretory machinery, glutamate release in the trisynaptic hippocampal excitatory pathway, and the behavioral evolution of kindling-induced epileptogenesis.

Method: Neurotransmitter release requires the fusion of vesicle and plasma membranes; it is initiated by formation of a stable, ternary complex (7SC) of SNARE [soluble N-ethylmaleimide sensitive factor (NSF) attachment protein receptor] proteins. Quantitative Western blotting was used to monitor levels of 7SC and SNARE regulators [NSF, SV2 (synaptic vesicle protein 2)] in hippocampal synaptosomes from amygdala-kindled animals. Hippocampal synaptic glutamate release was measured in vivo with a unique microelectrode array (MEA) that uses glutamate oxidase to catalyze the breakdown of glutamate into a reporter molecule.

Key findings: Ipsilateral hippocampal accumulation of 7SC developed with onset of amygdalar kindling, but became permanent only in animals stimulated to at least Racine stage 3; the ratio peaked and did not increase with more than two consecutive stage 5 seizures. Chronic 7SC asymmetry was seen in entorhinal cortex and the hippocampal formation, particularly in dentate gyrus (DG) and CA1, but not in the other brain areas examined. There was a strong correlation between asymmetric 7SC accumulation and increased total hippocampal SV2. Following a 30-day latent period, amplitudes of spontaneous synaptic glutamate release were enhanced in ipsilateral DG and reduced in ipsilateral CA3 of kindled animals; increased volleys of synaptic glutamate activity were seen in ipsilateral CA1.

Significance: Amygdalar kindling is associated with chronic changes in the flow of glutamate signaling in the excitatory trisynaptic pathway and with early but permanent changes in the mechanics of vesicular release in ipsilateral hippocampal formation.

Publication types

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

MeSH terms

  • Amygdala / physiopathology
  • Animals
  • Disease Models, Animal
  • Electric Stimulation / methods
  • Electrodes, Implanted
  • Electroencephalography
  • Glutamic Acid / metabolism*
  • Hippocampus / metabolism*
  • Kindling, Neurologic / metabolism*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • SNARE Proteins / metabolism*
  • Seizures / metabolism*
  • Seizures / physiopathology
  • Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins / metabolism
  • Synaptosomes / metabolism


  • SNARE Proteins
  • Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
  • Glutamic Acid