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An axon-specific expression of HCN channels catalyzes fast action potential signaling in GABAergic interneurons.

ABSTRACT: During high-frequency network activities, fast-spiking, parvalbumin-expressing basket cells (PV+-BCs) generate barrages of fast synaptic inhibition to control the probability and precise timing of action potential (AP) initiation in principal neurons. Here we describe a subcellular specialization that contributes to the high speed of synaptic inhibition mediated by PV+-BCs. Mapping of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel distribution in rat hippocampal PV+-BCs with subcellular patch-clamp methods revealed that functional HCN channels are exclusively expressed in axons and completely absent from somata and dendrites. HCN channels not only enhance AP initiation during sustained high-frequency firing but also speed up the propagation of AP trains in PV+-BC axons by dynamically opposing the hyperpolarization produced by Na+-K+ ATPases. Since axonal AP signaling determines the timing of synaptic communication, the axon-specific expression of HCN channels represents a specialization for PV+-BCs to operate at high speed.

SUBMITTER: Roth FC

PROVIDER: S-EPMC7206118 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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An axon-specific expression of HCN channels catalyzes fast action potential signaling in GABAergic interneurons.

Roth Fabian C FC Hu Hua H

Nature communications 20200507 1

During high-frequency network activities, fast-spiking, parvalbumin-expressing basket cells (PV<sup>+</sup>-BCs) generate barrages of fast synaptic inhibition to control the probability and precise timing of action potential (AP) initiation in principal neurons. Here we describe a subcellular specialization that contributes to the high speed of synaptic inhibition mediated by PV<sup>+</sup>-BCs. Mapping of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel distribution in rat hipp ...[more]

PMID: 32382046

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Project description:Fast-spiking (FS) interneurons are important elements of neocortical circuitry that constitute the primary source of synaptic inhibition in adult cortex and impart temporal organization on ongoing cortical activity. The highly specialized intrinsic membrane and firing properties that allow cortical FS interneurons to perform these functions are attributable to equally specialized gene expression, which is ultimately coordinated by cell-type-specific transcriptional regulation. Although embryonic transcriptional events govern the initial steps of cell-type specification in most cortical interneurons, including FS cells, the electrophysiological properties that distinguish adult cortical cell types emerge relatively late in postnatal development, and the transcriptional events that drive this maturational process are not known. To address this, we used mouse whole-genome microarrays and whole-cell patch clamp to characterize the transcriptional and electrophysiological maturation of cortical FS interneurons between postnatal day 7 (P7) and P40. We found that the intrinsic and synaptic physiology of FS cells undergoes profound regulation over the first 4 postnatal weeks and that these changes are correlated with primarily monotonic but bidirectional transcriptional regulation of thousands of genes belonging to multiple functional classes. Using our microarray screen as a guide, we discovered that upregulation of two-pore K leak channels between P10 and P25 contributes to one of the major differences between the intrinsic membrane properties of immature and adult FS cells and found a number of other candidate genes that likely confer cell-type specificity on mature FS cells. Experiment Overall Design: We characterized the transcriptional maturation of genetically labeled FS interneurons in mouse S1 cortex using whole-genome microarrays.mRNA was harvested from manually sorted GFPexpressing neurons dissociated from acutely prepared brain slices at a range of developmental time points (P7, P10, P15, P25, and P40) and subsequently reverse transcribed, amplified, labeled, and hybridized to Affymetrix 430 2.0 whole-genome microarrays (three microarrays from three different animals per condition). We used the G42 transgenic mice described by Chattopadhyaya et al. (2004) for all experiments.

Dataset Information

An axon-specific expression of HCN channels catalyzes fast action potential signaling in GABAergic interneurons.

Publications

An axon-specific expression of HCN channels catalyzes fast action potential signaling in GABAergic interneurons.

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