Accelerated hippocampal spreading depression and enhanced locomotory activity in mice with astrocyte-directed inactivation of connexin43.
The propagation of sustained potential shifts associated with spreading depression (SD) was studied by microelectrodes placed in diverse layers at different locations in hippocampus of anesthetized rats. SD was induced by raising interstitial potassium concentration ([K+]0) focally in the CA1 region of the dorsal hippocampus either by microdialysis or by microinjection. Recurrent waves of SD propagated from the dialysis site throughout the hippocampus. Potential shifts (delta V0) associated with SD usually began earlier and were always of larger amplitude and longer duration in stratum (st.) radiatum (layer of apical dendrites) than in st. pyramidale (layer of pyramidal cell somata). The velocity of propagation in the two layers differed and varied independently one from the other. When SD was provoked by orthodromic train stimuli, the apparent direction of propagation in st. pyramidale was opposite that in st. radiatum. Microinjection of high K+ solution was more likely to provoke SD when placed in the st. radiatum, 50-100 microns ventral to st. pyramidale, than in other cytoarchitectonic layers. In about half the trials after 30 to 90 min of high K+ dialysis, a prolonged depressed state developed during which the potential in st. radiatum shifted at irregular intervals between near-rest level and a strongly negative level, while delta V0 shifts in st. pyramidale were smaller and more irregular in amplitude. This state is termed prolonged unstable SD". When the NMDA receptor antagonist CPP was dialyzed together with high K+, the onset of SD was postponed and delta V0 waves propagated in st. pyramidale without corresponding waves in st. radiatum; less frequently the other way around.(ABSTRACT TRUNCATED AT 250 WORDS)