Low-magnesium medium induces epileptiform activity in mouse olfactory bulb slices

J Neurophysiol. 2011 Nov;106(5):2593-605. doi: 10.1152/jn.00601.2011. Epub 2011 Aug 10.

Abstract

Magnesium-free medium can be used in brain slice studies to enhance glutamate receptor function, but this manipulation causes seizure-like activity in many cortical areas. The rodent olfactory bulb (OB) slice is a popular preparation, and potentially ictogenic ionic conditions have often been used to study odor processing. We studied low Mg(2+)-induced epileptiform discharges in mouse OB slices using extracellular and whole cell electrophysiological recordings. Low-Mg(2+) medium induced two distinct types of epileptiform activity: an intraglomerular delta-frequency oscillation resembling slow sniff-induced activity and minute-long seizure-like events (SLEs) consisting of large negative-going field potentials accompanied by sustained depolarization of output neurons. SLEs were dependent on N-methyl-D-aspartate receptors and sodium currents and were facilitated by α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors. The events were initiated in the glomerular layer and propagated laterally through the external plexiform layer at a slow time scale. Our findings confirm that low-Mg(2+) medium should be used with caution in OB slices. Furthermore, the SLEs resembled the so-called slow direct current (DC) shift of clinical and experimental seizures, which has recently been recognized as being of great clinical importance. The OB slice may therefore provide a robust and unique in vitro model of acute seizures in which mechanisms of epileptiform DC shifts can be studied in isolation from fast oscillations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Acute Disease
  • Animals
  • Animals, Outbred Strains
  • Anticonvulsants / pharmacology
  • Culture Media / pharmacology
  • Electrophysiology / methods
  • Epilepsy, Generalized / drug therapy
  • Epilepsy, Generalized / metabolism
  • Epilepsy, Generalized / physiopathology*
  • Glutamic Acid / metabolism
  • Magnesium / metabolism*
  • Magnesium / pharmacology
  • Magnesium Deficiency / metabolism
  • Magnesium Deficiency / physiopathology*
  • Male
  • Mice
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neurons / physiology
  • Olfactory Bulb / cytology
  • Olfactory Bulb / metabolism
  • Olfactory Bulb / physiopathology*
  • Organ Culture Techniques
  • Phenytoin / pharmacology
  • Potassium / metabolism
  • Potassium / pharmacology
  • Receptors, AMPA / physiology
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Sodium / metabolism
  • gamma-Aminobutyric Acid / physiology

Substances

  • Anticonvulsants
  • Culture Media
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Phenytoin
  • Sodium
  • Magnesium
  • Potassium