Low-magnesium medium induces epileptiform activity in mouse olfactory bulb slices
Kajsa M Igelström1, Cristina H Shirley, Philip M Heyward
1Dept. of Physiology, Univ. of Otago, PO Box 913, Dunedin 9054, New Zealand. kajsa.igelstrom@otago.ac.nz
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.
Insights
Low magnesium in olfactory bulb slices induces seizure-like events, mimicking clinical seizures. Caution is advised when using this method to study brain activity.
Area of Science:
- Neuroscience
- Electrophysiology
- Epilepsy Research
Background:
- Magnesium-free medium enhances glutamate receptor function but can induce seizure-like activity.
- The rodent olfactory bulb (OB) slice is a common model for studying odor processing.
- Ictogenic (seizure-inducing) conditions are sometimes used in OB slice preparations.
Purpose of the Study:
- To investigate low magnesium (Mg2+)-induced epileptiform discharges in mouse OB slices.
- To characterize the nature and mechanisms of these seizure-like events (SLEs).
- To evaluate the OB slice as a model for studying seizure mechanisms, particularly slow direct current (DC) shifts.
Main Methods:
- Extracellular and whole-cell electrophysiological recordings in mouse OB slices.
- Induction of epileptiform activity using low-Mg2+ medium.
- Pharmacological manipulation to assess the role of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors and sodium currents.
Main Results:
- Low-Mg2+ induced two distinct activities: delta-frequency oscillations and minute-long SLEs.
- SLEs involved sustained depolarization of output neurons and were dependent on NMDA receptors and sodium currents.
- AMPA receptors facilitated SLEs, which initiated in the glomerular layer and propagated slowly.
Conclusions:
- Low-Mg2+ medium should be used cautiously in OB slices due to induced seizure-like activity.
- The observed SLEs resemble clinically relevant slow DC shifts in seizures.
- The OB slice offers a valuable in vitro model for studying isolated epileptiform DC shifts in acute seizures.
