Activity-dependent depression of excitability and calcium transients in the neurohypophysis suggests a model of "stuttering conduction".
Using millisecond time-resolved optical recordings of transmembrane voltage and intraterminal calcium, we have determined how activity-dependent changes in the population action potential are related to a concurrent modulation of calcium transients in the neurohypophysis. We find that repetitive stimulation dramatically alters the amplitude of the population action potential and significantly increases its temporal dispersion. The population action potentials and the calcium transients exhibit well correlated frequency-dependent amplitude depression, with broadening of the action potential playing only a limited role. High-speed camera recordings indicate that the magnitude of the spike modulation is uniform throughout the neurohypophysis, thereby excluding propagation failure as the underlying mechanism. In contrast, temporal dispersion and latency of the population spike do increase with distance from the stimulation site. This increase is enhanced during repeated stimulation and by raising the stimulation frequency. Changes in Ca influx directly affect the decline in population spike amplitude, consistent with electrophysiological measurements of the local loss of excitability in nerve terminals and varicosities, mediated by a Ca-activated K conductance. Our observations suggest a model of "stuttering conduction": repeated action potential stimulation causes excitability failures limited to nerve terminals and varicosities, which account for the rapid decline in the population spike amplitude. These failures, however, do not block action potential propagation but generate the cumulative increases in spike latency.
Muschol
Martin
M
Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6074, USA.
Kosterin
Paul
P
Ichikawa
Michinori
M
Salzberg
B M
BM
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D046508:Culture Techniques; D004553:Electric Conductivity; D004558:Electric Stimulation; D005260:Female; D005456:Fluorescent Dyes; D008564:Membrane Potentials; D051379:Mice; D008959:Models, Neurological; D009433:Neural Inhibition; D010904:Pituitary Gland, Posterior / Q000378:metabolism* / Q000502:physiology*
D005456:Fluorescent Dyes; D002118:Calcium