title: Cell type-specific synaptic dynamics of synchronized bursting in the juvenile CA3 rat hippocampus.
abstract: Spontaneous synchronous bursting of the CA3 hippocampus in vitro is a widely studied model of physiological and pathological network synchronization. The role of inhibitory conductances during network bursting is not understood in detail, despite the fact that several antiepileptic drugs target GABA(A) receptors. Here, we show that the first manifestation of a burst event is a cell type-specific flurry of GABA(A) receptor-mediated inhibitory input to pyramidal cells, but not to stratum oriens horizontal interneurons. Moreover, GABA(A) receptor-mediated synaptic input is proportionally smaller in these interneurons compared with pyramidal cells. Computational models and dynamic-clamp studies using experimentally derived conductance waveforms indicate that both these factors modulate spike timing during synchronized activity. In particular, the different kinetics and the larger strength of GABAergic input to pyramidal cells defer action potential initiation and contribute to the observed delay of firing, so that the interneuronal activity leads the burst cycle. In contrast, excitatory inputs to both neuronal populations during a burst are kinetically similar, as required to maintain synchronicity. We also show that the natural pattern of activation of inhibitory and excitatory conductances during a synchronized burst cycle is different within the same neuronal population. In particular, GABA(A) receptor-mediated currents activate earlier and outlast the excitatory components driving the bursts. Thus, cell type-specific balance and timing of GABA(A) receptor-mediated input are critical to set the appropriate spike timing in pyramidal cells and interneurons and coordinate additional neurotransmitter release modulating burst strength and network frequency.
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Aradi
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Maccaferri
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002712:Chlorides / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D011963:Receptors, GABA-A / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D002712:Chlorides; D058787:GABA-A Receptor Antagonists; D011724:Pyridazines; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C049853:gabazine