HCN1 hyperpolarization-activated cyclic nucleotide-gated channels enhance evoked GABA release from parvalbumin-positive interneurons.

Proc Natl Acad Sci U S A

Departments of Neuroscience and Pharmacology, Kavli Institute for Brain Science, Zuckerman Mind Brain Behavior Institute, Columbia University Medical Center, New York, NY 10027.

Published: October 2024

AI Article Synopsis

  • HCN channels, particularly HCN1, play a crucial role in regulating neuronal excitability and are found in both pyramidal neurons and parvalbumin-positive interneurons in the hippocampus.
  • This study used various advanced techniques to explore how HCN1 channels affect the release of GABA, an inhibitory neurotransmitter, from the axon terminals of these interneurons.
  • Findings revealed that blocking HCN1 reduced GABA release, showcasing its importance in facilitating inhibitory signaling in the hippocampal CA1 region.

Article Abstract

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels generate the cationic I current in neurons and regulate the excitability of neuronal networks. The function of HCN channels depends, in part, on their subcellular localization. Of the four HCN isoforms (HCN1-4), HCN1 is strongly expressed in the dendrites of pyramidal neurons (PNs) in hippocampal area CA1 but also in presynaptic terminals of parvalbumin-positive interneurons (PV+ INs), which provide strong inhibitory control over hippocampal activity. Yet, little is known about how HCN1 channels in these cells regulate the evoked release of the inhibitory transmitter GABA from their axon terminals. Here, we used genetic, optogenetic, electrophysiological, and imaging techniques to investigate how the electrophysiological properties of PV+ INs are regulated by HCN1, including how HCN1 activity at presynaptic terminals regulates the release of GABA onto PNs in CA1. We found that application of HCN1 pharmacological blockers reduced the amplitude of the inhibitory postsynaptic potential recorded from CA1 PNs in response to selective optogenetic stimulation of PV+ INs. Homozygous HCN1 knockout mice also show reduced IPSCs in postsynaptic cells. Finally, two-photon imaging using genetically encoded fluorescent calcium indicators revealed that HCN1 blockers reduced the probability that an extracellular electrical stimulating pulse evoked a Ca response in individual PV+ IN presynaptic boutons. Taken together, our results show that HCN1 channels in the axon terminals of PV+ interneurons facilitate GABAergic transmission in the hippocampal CA1 region.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494348PMC
http://dx.doi.org/10.1073/pnas.2319246121DOI Listing

Publication Analysis

Top Keywords

pv+ ins
12
hcn1
9
hyperpolarization-activated cyclic
8
cyclic nucleotide-gated
8
parvalbumin-positive interneurons
8
hcn channels
8
presynaptic terminals
8
hcn1 channels
8
axon terminals
8
blockers reduced
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!