Role of neuronal synchronizing mechanisms in the propagation of spreading depression in the in vivo hippocampus

摘要

To detect what initiates spreading depression (SD), the early prodromal events were investigated in hippocampal CA1 of urethane-anesthetized rats. SD was provoked by microdialysis or focal microinjection of high- K+ solution. Extracellular DC potentials and extracellular potassium concentration ([K+]o) were recorded, and spontaneous and evoked potentials analyzed for current source-density (CSD). In the front of an approaching SD wave, several seconds before the onset of the typical sustained negative potential shift (delta Vo) 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 wavelets and PSs were synchronized over considerable distances in the tissue. Sawtooth wavelets were identified as pacemakers of the prodromal PS burst. Simultaneous recording at three depths revealed that the spontaneous prodromal PSs occurred exactly in phase in dendrites and somata whereas synaptically transmitted PSs arose first in the proximal dendrites 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 subside. Blocking synaptic transmission did not abolish the prodromal spike burst, yet repetitive orthodromic activation inhibited it without altering the subsequent SD waveform. Complex changes in cell excitability were detected even before fast spontaneous activities. We concluded that, in the initial evolution of SD, changes in neuron function precede the regenerating depolarization by several seconds. We propose that the opening of normally closed electric junctions among neurons can best explain the long-distance synchronization and the flow current that occurs in the leading edge of a propagating wave of SD.