ROLE OF NEURONAL SYNCHRONIZING MECHANISMS IN THE PROPAGATION OF SPREADING DEPRESSION IN THE IN-VIVO HIPPOCAMPUS

To detect what initiates spreading depression (SD), the early prodroma l events were investigated in hippocampal CA1 of urethane-anesthetized rats. SD was provoked by microdialysis or focal microinjection of hig h-K+ solution. Extracellular DC potentials and extracellular potassium concentration ([K+](o)) were recorded, and spontaneous and evoked pot entials analyzed for current source-density (CSD). In the front of an approaching SD wave, several seconds before the onset of the typical s ustained negative potential shift (Delta V-o) and the increased [K+](o ), fast electrical activity was detected. This consisted initially of small rhythmic (60-70 Hz) sawtooth wavelets, which then gave way to a shower of population spikes (PSs) of identical frequency. Prodromal wa velets and PSs were synchronized over considerable distances in the ti ssue. Sawtooth wavelets were identified as pacemakers of the prodromal PS burst. Simultaneous recording at three depths revealed that the sp ontaneous prodromal PSs occurred exactly in phase in dendrites and som ata whereas synaptically transmitted PSs arose first in the proximal d endrites and were conducted from there into the soma membrane. During a spike burst, stratum (st.) pyramidale served as current sink, while in the proximal sublayer of st. radiatum spike-sinks gave way to spike sources that grew larger as the sinks in st. pyramidale began to subs ide. Blocking synaptic transmission did not abolish the prodromal spik e burst, yet repetitive orthodromic activation inhibited it without al tering the subsequent SD waveform. Complex changes in cell excitabilit y were detected even before fast spontaneous activities. We concluded that, in the initial evolution of SD, changes in neuron function prece de the regenerating depolarization by several seconds. We propose that the opening of normally closed electric junctions among neurons can b est explain the long-distance synchronization and the flow current tha t occurs in the leading edge of a propagating wave of SD.