title: Differential modulation of phasic and tonic inhibition underlies serotonergic suppression of long-term potentiation in the rat visual cortex.
abstract: GABA receptor type A (GABA(A)R)-mediated inhibition is divided into phasic and tonic inhibition. GABA(A)Rs mediating the two inhibitory modalities exhibit differences in subcellular localization and subunit composition. We previously demonstrated that phasic and tonic inhibition are independently regulated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and protein kinase A (PKA), respectively. Since modulation of GABA(A)Rs by phosphorylation differs depending on subunit composition and protein kinases, phasic and tonic inhibition might be differentially regulated by a single neuromodulator activating multiple protein kinases. However, the neuromodulatory control for phasic and tonic inhibition is largely unknown. Thus, in the present study, we concurrently investigated the serotonin (5-HT) regulation of phasic and tonic inhibition and its functional implication in the pyramidal neurons of the rat visual cortex. Interestingly, 5-HT enhanced phasic inhibition but suppressed tonic inhibition. Increase in phasic inhibition was mediated by 5-HT2 receptor and CaMKII, whereas decrease in tonic inhibition depended on 5-HT1A receptor and PKA. Thus, phasic and tonic inhibition might be independently regulated even by a single neuromodulator. Functionally, the opposite modulation of phasic and tonic inhibition decreased the summation of consecutive excitatory postsynaptic potentials (EPSPs) without affecting the shape of single EPSPs, which might underlie the suppression of the induction of long-term potentiation by 5-HT. These results suggest that the integrative regulation of phasic and tonic inhibition provides mechanisms for elaborate modulation of shape and summation of EPSPs and long-term synaptic plasticity.
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Catholic Neuroscience Institute, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Jang
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: K-H
authors.initials: KH
authors.lastname: Cho
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: K
authors.initials: K
authors.lastname: Joo
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: M-J
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Catholic Neuroscience Institute, The Catholic University of Korea, Seoul 137-701, Republic of Korea. Electronic address: djrhie@catholic.ac.kr.
authors.forename: D-J
authors.initials: DJ
authors.lastname: Rhie
mesh_terms: D000818:Animals; D004347:Drug Interactions; D004558:Electric Stimulation; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D059326:Serotonergic Neurons / Q000187:drug effects / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology; D014793:Visual Cortex / Q000166:cytology*
chemical_list: D018683:Excitatory Amino Acid Agents; D018682:GABA Agents; D047908:Intracellular Signaling Peptides and Proteins; D018490:Serotonin Agents; C015482:protein kinase modulator
keywords: 5-HT; CaMKII; GABA(A) receptor; LTP; PKA; summation