title: Persistent discharges in dentate gyrus perisoma-inhibiting interneurons require hyperpolarization-activated cyclic nucleotide-gated channel activation.
abstract: Parvalbumin (PV)-expressing perisoma-inhibiting interneurons (PIIs) of the dentate gyrus integrate rapidly correlated synaptic inputs and generate short-duration action potentials that propagate along the axon to their output synapses, supporting fast inhibitory signaling onto their target cells. Here we show that PV-PIIs in rat and mouse dentate gyrus (DG) integrate their intrinsic activity over time and can turn into a persistent firing mode characterized by the ability to generate long-lasting trains of action potentials at ∼50 Hz in the absence of additional inputs. Persistent firing emerges in the axons remote from the axon initial segment and markedly depends on hyperpolarization-activated cyclic nucleotide-gated channel (HCNC) activation. Persistent firing properties are modulated by intracellular Ca(2+) levels and somatic membrane potential. Detailed computational single-cell PIIs models reveal that HCNC-mediated conductances can contribute to persistent firing during conditions of a shift in their voltage activation curve to more depolarized potentials. Paired recordings from PIIs and their target granule cells show that persistent firing supports strong inhibitory output signaling. Thus, persistent firing may emerge during conditions of intense activation of the network, thereby providing silencing to the circuitry and the maintenance of sparse activity in the dentate gyrus.
authors.affiliation: Institute of Physiology I, Systemic and Cellular Neuroscience, Albert-Ludwigs University Freiburg, D-79104 Freiburg, Germany.
authors.forename: Claudio
authors.initials: C
authors.lastname: Elgueta
authors.affiliation: Institute of Physiology I, Systemic and Cellular Neuroscience, Albert-Ludwigs University Freiburg, D-79104 Freiburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Köhler
authors.affiliation: Institute of Physiology I, Systemic and Cellular Neuroscience, Albert-Ludwigs University Freiburg, D-79104 Freiburg, Germany marlene.bartos@physiologie.uni-freiburg.de.
authors.forename: Marlene
authors.initials: M
authors.lastname: Bartos
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001552:Benzazepines / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology*; D000077550:Ivabradine; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008959:Models, Neurological; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism; D019580:Perforant Pathway / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D055366:Synaptic Potentials / Q000187:drug effects / Q000235:genetics; D014162:Transfection
chemical_list: D001552:Benzazepines; D002316:Cardiotonic Agents; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D010320:Parvalbumins; D011743:Pyrimidines; C082246:ICI D2788; D000077550:Ivabradine
keywords: GABA; HCN; basket cell; dentate gyrus; interneuron; persistent firing