title: Elevated serotonergic signaling amplifies synaptic noise and facilitates the emergence of epileptiform network oscillations.
abstract: Serotonin fibers densely innervate the cortical sheath to regulate neuronal excitability, but its role in shaping network dynamics remains undetermined. We show that serotonin provides an excitatory tone to cortical neurons in the form of spontaneous synaptic noise through 5-HT3 receptors, which is persistent and can be augmented using fluoxetine, a selective serotonin re-uptake inhibitor. Augmented serotonin signaling also increases cortical network activity by enhancing synaptic excitation through activation of 5-HT2 receptors. This in turn facilitates the emergence of epileptiform network oscillations (10-16 Hz) known as fast runs. A computational model of cortical dynamics demonstrates that these two combined mechanisms, increased background synaptic noise and enhanced synaptic excitation, are sufficient to replicate the emergence fast runs and their statistics. Consistent with these findings, we show that blocking 5-HT2 receptors in vivo significantly raises the threshold for convulsant-induced seizures.
authors.affiliation: Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio; and.
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Puzerey
authors.affiliation: School of Nursing, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Decker
authors.affiliation: Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio; and rfgalan@case.edu.
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Galán
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005473:Fluoxetine / Q000494:pharmacology; D007650:Ketanserin; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010433:Pentylenetetrazole; D010507:Periodicity; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013003:Somatosensory Cortex / Q000187:drug effects / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013788:Thalamus / Q000187:drug effects / Q000503:physiopathology; D046509:Tissue Culture Techniques
chemical_list: D005473:Fluoxetine; D007650:Ketanserin; D010433:Pentylenetetrazole; D044348:Receptors, Serotonin, 5-HT2; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
keywords: 5-HT2 receptors; 5-HT3 receptors; cortical network dynamics; epileptic seizures; synaptic noise