title: Serotonin dependent masking of hippocampal sharp wave ripples.
abstract: Sharp wave ripples (SPW-Rs) are thought to play an important role in memory consolidation. By rapid replay of previously stored information during slow wave sleep and consummatory behavior, they result from the formation of neural ensembles during a learning period. Serotonin (5-HT), suggested to be able to modify SPW-Rs, can affect many neurons simultaneously by volume transmission and alter network functions in an orchestrated fashion. In acute slices from dorsal hippocampus, SPW-Rs can be induced by repeated high frequency stimulation that induces long-lasting LTP. We used this model to study SPW-R appearance and modulation by 5-HT. Although stimulation in presence of 5-HT permitted LTP induction, SPW-Rs were "masked"--but appeared after 5-HT wash-out. This SPW-R masking was dose dependent with 100 nM 5-HT being sufficient--if the 5-HT re-uptake inhibitor citalopram was present. Fenfluramine, a serotonin releaser, could also mask SPW-Rs. Masking was due to 5-HT1A and 5-HT2A/C receptor activation. Neither membrane potential nor membrane conductance changes in pyramidal cells caused SPW-R blockade since both remained unaffected by combining 5-HT and citalopram. Moreover, 10 and 30 μM 5-HT mediated SPW-R masking preceded neuronal hyperpolarization and involved reduced presynaptic transmitter release. 5-HT, as well as a 5-HT1A agonist, augmented paired pulse facilitation and affected the coefficient of variance. Spontaneous SPW-Rs in mice hippocampal slices were also masked by 5-HT and fenfluramine. While neuronal ensembles can acquire long lasting LTP during higher 5-HT levels, lower 5-HT levels enable neural ensembles to replay previously stored information and thereby permit memory consolidation memory.
authors.affiliation: Inst. Neurophysiology, Charité Universitätsmedizin, Berlin, Germany; Department of Pharmacy, Hazara University, Havelian Campus, 22500, Pakistan.
authors.forename: Rizwan
authors.initials: R
authors.lastname: ul Haq
authors.affiliation: Inst. Neurophysiology, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Marlene L
authors.initials: ML
authors.lastname: Anderson
authors.affiliation: Inst. Neurophysiology, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Jan-Oliver
authors.initials: JO
authors.lastname: Hollnagel
authors.affiliation: Inst. Neurophysiology, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Worschech
authors.affiliation: Department of Pharmacy, Hazara University, Havelian Campus, 22500, Pakistan.
authors.forename: Muhammad Azahr
authors.initials: MA
authors.lastname: Sherkheli
authors.affiliation: Inst. Neurophysiology, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Behrens
authors.affiliation: Inst. Neurophysiology, Charité Universitätsmedizin, Berlin, Germany; Neuroscience Research Center, Charité Universitätsmedizin, Berlin, Germany. Electronic address: Uwe.Heinemann@charite.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Heinemann
mesh_terms: D000818:Animals; D001703:Biophysics; D015283:Citalopram / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D009415:Nerve Net / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D018490:Serotonin Agents / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D018490:Serotonin Agents; D015283:Citalopram; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D012701:Serotonin
keywords: 5-HT; 5-HT(1A) receptors; 8-OH-DPAT; Citalopram; Fenfluramine; LTP; NAN-190; SPW-R