title: Learning-induced modulation of the GABAB-mediated inhibitory synaptic transmission: mechanisms and functional significance.
abstract: Complex olfactory-discrimination (OD) learning results in a series of intrinsic and excitatory synaptic modifications in piriform cortex pyramidal neurons that enhance the circuit excitability. Such overexcitation must be balanced to prevent runway activity while maintaining the efficient ability to store memories. We showed previously that OD learning is accompanied by enhancement of the GABAA-mediated inhibition. Here we show that GABAB-mediated inhibition is also enhanced after learning and study the mechanism underlying such enhancement and explore its functional role. We show that presynaptic, GABAB-mediated synaptic inhibition is enhanced after learning. In contrast, the population-average postsynaptic GABAB-mediated synaptic inhibition is unchanged, but its standard deviation is enhanced. Learning-induced reduction in paired pulse facilitation in the glutamatergic synapses interconnecting pyramidal neurons was abolished by application of the GABAB antagonist CGP55845 but not by blocking G protein-gated inwardly rectifying potassium channels only, indicating enhanced suppression of excitatory synaptic release via presynaptic GABAB-receptor activation. In addition, the correlation between the strengths of the early (GABAA-mediated) and late (GABAB-mediated) synaptic inhibition was much stronger for each particular neuron after learning. Consequently, GABAB-mediated inhibition was also more efficient in controlling epileptic-like activity induced by blocking GABAA receptors. We suggest that complex OD learning is accompanied by enhancement of the GABAB-mediated inhibition that enables the cortical network to store memories, while preventing uncontrolled activity.
authors.affiliation: Departments of Neurobiology and Biology, Faculty of Sciences, University of Haifa, Haifa, Israel; and.
authors.forename: Adi
authors.initials: A
authors.lastname: Kfir
authors.affiliation: Departments of Neurobiology and Biology, Faculty of Sciences, University of Haifa, Haifa, Israel; and.
authors.forename: Naama
authors.initials: N
authors.lastname: Ohad-Giwnewer
authors.affiliation: Departments of Neurobiology and Biology, Faculty of Sciences, University of Haifa, Haifa, Israel; and.
authors.forename: Luna
authors.initials: L
authors.lastname: Jammal
authors.affiliation: Departments of Neurobiology and Biology, Faculty of Sciences, University of Haifa, Haifa, Israel; and.
authors.forename: Drorit
authors.initials: D
authors.lastname: Saar
authors.affiliation: Department of Physiology and Neurobiology, Faculty of Health Sciences, and the Zlotowski Center for Neuroscience, Ben-Gurion University, BeerSheva, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Golomb
authors.affiliation: Departments of Neurobiology and Biology, Faculty of Sciences, University of Haifa, Haifa, Israel; and ebarkai@research.haifa.ac.il.
authors.forename: Edi
authors.initials: E
authors.lastname: Barkai
mesh_terms: D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology*; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D008839:Microelectrodes; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009483:Neuropsychological Tests; D055696:Olfactory Perception / Q000187:drug effects / Q000502:physiology*; D010721:Phosphinic Acids / Q000494:pharmacology; D066195:Piriform Cortex / Q000187:drug effects / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D046509:Tissue Culture Techniques
chemical_list: D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids; D024661:Potassium Channels, Inwardly Rectifying; D011412:Propanolamines; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C085075:CGP 55845A; D018698:Glutamic Acid
keywords: GABAB; brain slices; olfactory-discrimination learning; piriform cortex; synaptic inhibition