Desynchronization of glutamate release prolongs synchronous CA3 network activity.
Periodic bursts of activity in the disinhibited in vitro hippocampal CA3 network spread through the neural population by the glutamatergic recurrent collateral axons that link CA3 pyramidal cells. It was previously proposed that these bursts of activity are terminated by exhaustion of releasable glutamate at the recurrent collateral synapses so that the next periodic burst of network activity cannot occur until the supply of glutamate has been replenished. As a test of this hypothesis, the rate of glutamate release at CA3 axon terminals was reduced by substitution of extracellular Ca(2+) with Sr(2+). Reduction of the rate of glutamate release reduces the rate of depletion and should thereby prolong bursts. Here we demonstrate that Sr(2+) substitution prolongs spontaneous bursts in the disinhibited adult CA3 hippocampal slices to 37.2 +/- 7.6 (SE) times the duration in control conditions. Sr(2+) also decreased the probability of burst initiation and the rate of burst onset, consistent with reduced synchrony of glutamate release and a consequent reduced rate of spread of excitation through the slice. These findings support the supply of releasable glutamate as an important determinant of the probability and duration of synchronous CA3 network activity.
Jones
Jethro
J
Department of Pediatrics, University of Colorado Health Science Center, Denver, USA.
Stubblefield
Elizabeth A
EA
Benke
Timothy A
TA
Staley
Kevin J
KJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009415:Nerve Net / Q000378:metabolism*; D010507:Periodicity; D010852:Picrotoxin / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013324:Strontium / Q000494:pharmacology
D002118:Calcium; D018756:GABA Antagonists; D018698:Glutamic Acid; D010852:Picrotoxin; D013324:Strontium