Osmotic effects upon the theta rhythm, a natural brain oscillation in the hippocampal slice

Abstract

Raising plasma osmolality reduces patient susceptibility to generalized tonic-clonic seizure. In brain slices, elevated osmolality reduces epileptiform discharge. Conversely, lowering osmolality can induce generalized tonic-clonic seizure in patients and promotes epileptiform activity in hippocampal or neocortical slices. Rhythmic slow activity or "theta" encodes memory in some mammals and represents a nonpathological oscillation of cortical neurons. In hippocampal slices, theta consists of a 4-10 Hz oscillation overriding a slow depolarization (SD) that recurs periodically. We examined if the theta rhythm, which is a natural brain oscillation, was affected by clinically relevant changes in osmolality. Theta was induced by bath application of 40 microM carbachol and intracellularly recorded in individual CA3 neurons of the rat hippocampal slice. Artificial CSF (ACSF) elevated by 40 milliosmoles (+40 mOsm) using mannitol slowed the SD frequency in 18 of 18 CA3 neurons. Conversely -40 mOsm ACSF increased SD frequency in 12 of 14 neurons. Osmotic alteration did not change theta frequency in 9 of 9 CA3 cells, but overriding action potentials were reduced in number or eliminated by hyperosmotic ACSF in 8 of 12 neurons. Elevation of osmolality with glycerol, which does not alter cell volume, had no effect in 4 of 4 neurons. This indicated that the induced changes in excitability resulted from alterations in cell volume. We examined if osmotically induced changes in cell volume migh…