title: Synaptic activation of GABA(B) receptors regulates neuronal network activity and entrainment.
abstract: In the mammalian central nervous system, GABA(B) receptors mediate slow pre- and postsynaptic inhibition. Using rat hippocampal slices we investigated the role of synaptic GABA(B) receptors in regulating kainate-induced subthreshold neuronal network oscillations in the gamma frequency range (25-80 Hz). The GABA(B) receptor agonist baclofen largely eliminated gamma oscillations. The GABA(B) receptor antagonist CGP55845 reversed this action of baclofen but alone did not alter the power or frequency of ongoing oscillations. To examine the role of synaptically released GABA on network activity, we electrically stimulated stratum radiatum of CA3 whilst recording gamma oscillations from stratum pyramidale. Single stimuli produced a pronounced transient (up to 1 s in duration) inhibition of gamma frequency oscillations. This stimulus-induced shutdown of network activity was enhanced by the GABA uptake inhibitor tiagabine and largely inhibited by CGP55845. Multiple stimuli delivered at frequencies of 1-3 Hz resulted in an activity-dependent fatigue of the inhibition of gamma activity, such that, after a number of stimuli, oscillations could be detected tens of milliseconds after the stimulus. Interestingly, this activity-dependent fatigue of inhibition uncovered a stimulus-dependent temporal entrainment of the gamma oscillations. Furthermore, the amount of repetitive synaptic input that was required to cause this entrainment was dramatically reduced by GABA(B) receptor antagonism such that it was evident within just a few stimuli. These data suggest that convergent afferent synaptic activity can alter the precise temporal arrangement of neuronal network activity. Furthermore, the flow of such information into a functioning neuronal network is highly regulated by GABA(B) receptor-mediated synaptic inhibition.
authors.affiliation: Neurology and GI, GlaxoSmithKline, Harlow, Essex, UK. Jon.Brown@bristol.ac.uk
authors.forename: Jon T
authors.initials: JT
authors.lastname: Brown
authors.forename: Ceri H
authors.initials: CH
authors.lastname: Davies
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Randall
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D003344:Cortical Synchronization; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D018080:Receptors, GABA-B / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018690:Excitatory Amino Acid Agonists; D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid