title: HCN1 channels reduce the rate of exocytosis from a subset of cortical synaptic terminals.
abstract: The hyperpolarization-activated cyclic nucleotide-gated (HCN1) channels are predominantly located in pyramidal cell dendrites within the cortex. Recent evidence suggests these channels also exist pre-synaptically in a subset of synaptic terminals within the mature entorhinal cortex (EC). Inhibition of pre-synaptic HCN channels enhances miniature excitatory post-synaptic currents (mEPSCs) onto EC layer III pyramidal neurons, suggesting that these channels decrease the release of the neurotransmitter, glutamate. Thus, do pre-synaptic HCN channels alter the rate of synaptic vesicle exocytosis and thereby enhance neurotransmitter release? To address this, we imaged the release of FM1-43, a dye that is incorporated into synaptic vesicles, from EC synaptic terminals using two photon microscopy in slices obtained from forebrain specific HCN1 deficient mice, global HCN1 knockouts and their wildtype littermates. This coupled with electrophysiology and pharmacology showed that HCN1 channels restrict the rate of exocytosis from a subset of cortical synaptic terminals within the EC and in this way, constrain non-action potential-dependent and action potential-dependent spontaneous release as well as synchronous, evoked release. Since HCN1 channels also affect post-synaptic potential kinetics and integration, our results indicate that there are diverse ways by which HCN1 channels influence synaptic strength and plasticity.
authors.affiliation: UCL School of Pharmacy, University College London, London, WC1N 1AX, UK.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Huang
authors.affiliation: UCL School of Pharmacy, University College London, London, WC1N 1AX, UK.
authors.forename: Gengyu
authors.initials: G
authors.lastname: Li
authors.affiliation: Departamento de Ciencias Medicas, Universidad de Castilla-La Mancha, 02006 Albacete, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Aguado
authors.affiliation: Departamento de Ciencias Medicas, Universidad de Castilla-La Mancha, 02006 Albacete, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Lujan
authors.affiliation: UCL School of Pharmacy, University College London, London, WC1N 1AX, UK.
authors.forename: Mala M
authors.initials: MM
authors.lastname: Shah
mesh_terms: D000818:Animals; D003712:Dendrites / Q000502:physiology; D005089:Exocytosis; D005260:Female; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics / Q000502:physiology*; D008297:Male; D018345:Mice, Knockout; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D016548:Prosencephalon / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D055366:Synaptic Potentials
chemical_list: C578666:Hcn1 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels