title: GABA(B) receptors inhibit backpropagating dendritic spikes in hippocampal CA1 pyramidal cells in vivo.
abstract: Spike backpropagation has been proposed to enhance dendritic depolarization and synaptic plasticity. However, relatively little is known about the inhibitory control of spike backpropagation in vivo. In this study, the backpropagation of the antidromic spike into the dendrites of CA1 pyramidal cells was studied by extracellular recording in urethane-anesthetized rats. The population antidromic spike (pAS) in CA1 following stimulation of the alveus was recorded simultaneously with a 16-channel silicon probe and analyzed as current source density (CSD). The pAS current sink was shown to sequentially invade the soma and then the apical and basal dendrites. When the pAS was preceded <400 ms by a conditioning orthodromic CA3 stimulus, the apical and basal dendritic spike sinks were reduced and delayed. Dendritic spike suppression was large after a high-intensity CA3 conditioning stimulus that evoked a population spike, small after a low-intensity CA3 conditioning stimulus, and weak after conditioning by another pAS. The late (150-400 ms latency) inhibition of the backpropagating pAS at the apical and basal dendrites was partially relieved by a GABA(B) receptor antagonist, CGP35348 or CGP56999A, given intracerebroventricularly (icv). CGP35348 icv also decreased the latency of the antidromic spike sinks at all depths. A compartment cable model of a CA1 pyramidal cell with excitable dendrites, combined with a model of extracellular potential generation, confirms that GABA(B) receptor activation delays a backpropagating spike and blocks distal dendritic spikes. GABA(B) receptor-mediated conductance increase and hyperpolarization, amplified by removing dendritic I(A) inactivation, contribute to conditioned dendritic spike suppression. In addition, the model shows that slow Na(+) channel inactivation also participates in conditioned spike suppression, which may partly explain the small dendritic spike suppression after conditioning with a weak orthodromic stimulus or another antidromic spike. Thus, both theory and experiment confirm an important role of the GABA(B) receptors in controlling dendritic spike backpropagation.
authors.affiliation: Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada. sleung@uwo.ca
authors.forename: L Stan
authors.initials: LS
authors.lastname: Leung
authors.forename: Pascal
authors.initials: P
authors.lastname: Peloquin
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D008959:Models, Neurological; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D018080:Receptors, GABA-B / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D018080:Receptors, GABA-B; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D005680:gamma-Aminobutyric Acid