title: Control of feedforward dendritic inhibition by NMDA receptor-dependent spike timing in hippocampal interneurons.
abstract: Two putative functional populations of feedforward interneurons with distinct spike-timing properties were identified in stratum radiatum of the CA1 rat hippocampus. Interneurons with fast (half width, <100 msec) EPSPs fired after short EPSP-spike latencies and with a high degree of temporal precision compared with cells with slow (half width, >100 msec) EPSPs. Spike timing in fast and slow interneurons occurred at different phases of the EPSPs of simultaneously activated pyramidal cells. In addition, firing of fast interneurons preceded action potentials in principal neurons, whereas action potentials in slow interneurons could either precede or follow firing in pyramidal cells. Temporal integration of separate inputs leading to synaptically evoked firing was more prominent in slow than fast interneurons. Functional diversity between the two putative populations was abolished by the NMDA receptor (NMDAR) antagonist d-(-)-2-amino-5-phosphonopentanoic acid (d-AP-5). The axon of both cell types was primarily restricted to striatum radiatum or to striatum lacunosum-moleculare in the case of slow cells, suggesting targeting of principal cell dendrites for the majority of the cells of this study. Indeed, firing of slow and fast interneurons generated similar unitary IPSCs (uIPSCs) in pyramidal neurons. uIPSCs were mediated by GABA(A) receptors and had in most cases small amplitudes and slow kinetics. Our results suggest that functionally heterogeneous interneurons encode the temporal properties of dendritic feedforward inhibition, and that NMDARs play an essential role in shaping the integrative properties of interneurons and in setting the timing of GABA release.
authors.affiliation: Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Maccaferri
authors.forename: Raymond
authors.initials: R
authors.lastname: Dingledine
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D025461:Feedback, Physiological; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007395:Interneurons / Q000145:classification / Q000502:physiology*; D007700:Kinetics; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; D015763:2-Amino-5-phosphonovalerate