title: Synaptic Mechanisms of Tight Spike Synchrony at Gamma Frequency in Cerebral Cortex.
abstract: During the generation of higher-frequency (e.g., gamma) oscillations, cortical neurons can exhibit pairwise tight (<10 ms) spike synchrony. To understand how synaptic currents contribute to rhythmic activity and spike synchrony, we performed dual whole-cell recordings in mouse entorhinal cortical slices generating periodic activity (the slow oscillation). This preparation exhibited a significant amount of gamma-coherent spike synchrony during the active phase of the slow oscillation (Up state), particularly among fast-spiking inhibitory interneurons. IPSCs arriving in pairs of either pyramidal or fast-spiking neurons during the Up state were highly synchronized and exhibited significant coherence at frequencies from 10 to 100 Hz, peaking at ∼40 Hz, suggesting both synchronous discharge of, and synaptic divergence from, nearby inhibitory neurons. By inferring synaptic currents related to spike generation in simultaneously recorded pyramidal or fast-spiking neurons, we detected a decay of inhibition ∼20 ms before spiking. In fast-spiking interneurons, this was followed by an even larger excitatory input immediately before spike generation. Consistent with an important role for phasic excitation in driving spiking, we found that the correlation of excitatory inputs was highly predictive of spike synchrony in pairs of fast-spiking interneurons. Interestingly, spike synchrony in fast-spiking interneurons was not related to the strength of gap junctional coupling, and was still prevalent in connexin 36 knock-out animals. Our results support the pyramidal-interneuron gamma model of fast rhythmic oscillation in the cerebral cortex and suggest that spike synchrony and phase preference arises from the precise interaction of excitatory-inhibitory postsynaptic currents.
  
  
  CONCLUSIONS
  We dissected the cellular and synaptic basis of spike synchrony occurring at gamma frequency (30-80 Hz). We used simultaneous targeted whole-cell recordings in an active slice preparation and analyzed the relationships between synaptic inputs and spike generation. We found that both pyramidal and fast-spiking neurons receive large, coherent inhibitory synaptic inputs at gamma frequency. In addition, we found that fast-spiking interneurons receive large, phasic excitatory synaptic inputs immediately before spike generation followed shortly by synaptic inhibition. These data support the principal-interneuron gamma generation model, and reveal how the synaptic connectivity between excitatory and inhibitory neurons supports the generation of gamma oscillations and spike synchrony.
authors.affiliation: Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: David B
authors.initials: DB
authors.lastname: Salkoff
authors.affiliation: Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: Edward
authors.initials: E
authors.lastname: Zagha
authors.affiliation: Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: Özge
authors.identifier: http://orcid.org/0000-0003-1690-5990
authors.initials: Ö
authors.lastname: Yüzgeç
authors.affiliation: Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510 david.mccormick@yale.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: McCormick
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology* / Q000502:physiology*; D017630:Connexins / Q000378:metabolism; D004558:Electric Stimulation; D065818:Gamma Rhythm / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D013057:Spectrum Analysis; D018709:Statistics, Nonparametric; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D000097004:Gap Junction delta-2 Protein
chemical_list: D017630:Connexins; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D000097004:Gap Junction delta-2 Protein; C486303:Dscr1l1 protein, mouse; C485184:enhanced green fluorescent protein
keywords: active slice; entorhinal cortex; fast-spiking interneurons; gamma rhythm; gap junctions; synchrony