HCAR1-mediated lactate signaling modulates motor behavior and regulates spontaneous firing in Purkinje cells.

Overview

Authors: Francesca Binda¹, Lara Buscemi^1,2, Nicolas Gurtner¹, Lorenz Hirt^1,2, Jean-Yves Chatton^1,3

ORCID iDs: Francesca Binda, Jean-Yves Chatton

Department of Fundamental Neurosciences, University of Lausanne, 1005 Lausanne, Switzerland
Stroke Laboratory, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital Centre and University of Lausanne, 1011 Lausanne, Switzerland
Cellular Imaging Facility, University of Lausanne, 1005 Lausanne, Switzerland

Institutions: University of Lausanne (Switzerland); Centre Hospitalier Universitaire Vaudois (Switzerland)

Journal: iScience, volume 29, issue 8, article 116930

Dates: received 5 September 2025; accepted 9 July 2026; published online 3 August 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1016/j.isci.2026.116930 · PMID 42597666 · PMCID PMC13470098 · OpenAlex W7172270168

Open access: gold, a free copy (OpenAlex)

Status: code on request

Categories: cellular / molecular (subfield)

Methods: Statistics, Connectivity, Single-unit activity, calcium imaging

Keywords: lactate, HCAR1, cerebellum, Purkinje cells, HCN, spontaneous firing, hydroxycarboxylic acid receptor 1, motor learning, glia

Topic: Neuroscience and Neuropharmacology Research (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex

Funding: Swiss National Science Foundation

Citations: not cited yet (Europe PMC); 89 references in the paper

Research resources: Mouse monoclonal Anti-NeuN RRID:AB_2298772, Rabbit polyclonal anti-Parvalbumin RRID:AB_2315235, RRID:AB_2534105, RRID:AB_2535792, RRID:AB_2762823, Goat polyclonal anti-TdTomato RRID:AB_2827808, Rabbit polyclonal anti-Calbindin RRID:AB_3107026, GraphPad Prism RRID:SCR_002798, ImageJ RRID:SCR_003070, pClamp RRID:SCR_011323

Abstract

Lactate modulates several phenomena ranging from gene transcription to plasticity. Through its specific GPCR receptor HCAR1, lactate acts as a signaling molecule modulating neuronal excitability. Silencing lactate signaling promotes anxiety-like behavior and worsens epileptic seizures, highlighting the central role of HCAR1 in brain function.

HCAR1 expression in the cerebellum supports the role of the receptor in motor coordination. Early experimental evidence suggesting HCAR1 expression in cerebellar Purkinje cells (PCs) together with its ability to modulate neuronal excitability qualifies the receptor as a possible modulator of PC activity with important implications for cerebellar-mediated diseases.

This hypothesis was investigated using behavioral analysis and ex vivo electrophysiology that showed gait instability and motor learning defects in HCAR1 knockout mice associated with increased PC firing. We identified HCN channels as the downstream target of HCAR1.

We conclude that lactate signaling is a modulator of PC excitability and revealed the HCAR1 role in motor behavior.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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The paper's code and data availability statement is in the Data section.

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Data

Datasets cited

zenodo:20341820, at Zenodo; found in “Data and code availability”

Data and code availability

Data have been deposited at https://doi.org/10.5281/zenodo.20341820 and are publicly available as of the date of publication.

This paper does not report original code.

Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 3, 28 September 2026

Authors: added Francesca Binda (0009-0001-7633-650X); Jean-Yves Chatton (0000-0002-8911-0315); removed Francesca Binda; Jean-Yves Chatton

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 9 keywords, 1 funder, 89 references, 10 RRIDs.

Cite

This paper

Binda, F., Buscemi, L., Gurtner, N., Hirt, L., & Chatton, J.-Y. (2026). HCAR1-mediated lactate signaling modulates motor behavior and regulates spontaneous firing in Purkinje cells. iScience, 29(8), 116930. https://doi.org/10.1016/j.isci.2026.116930

BibTeX

@article{binda2026hcar1, author = {Binda, Francesca and Buscemi, Lara and Gurtner, Nicolas and Hirt, Lorenz and Chatton, Jean-Yves}, title = {{HCAR1-mediated lactate signaling modulates motor behavior and regulates spontaneous firing in Purkinje cells}}, journal = {iScience}, year = {2026}, month = aug, volume = {29}, number = {8}, pages = {116930}, publisher = {Elsevier}, issn = {2589-0042}, doi = {10.1016/j.isci.2026.116930}, url = {https://doi.org/10.1016/j.isci.2026.116930}, pmid = {42597666}, pmcid = {PMC13470098} }

RIS

TY - JOUR AU - Binda, Francesca AU - Buscemi, Lara AU - Gurtner, Nicolas AU - Hirt, Lorenz AU - Chatton, Jean-Yves TI - HCAR1-mediated lactate signaling modulates motor behavior and regulates spontaneous firing in Purkinje cells T2 - iScience J2 - iScience PY - 2026 DA - 2026/08/03 VL - 29 IS - 8 SP - 116930 SN - 2589-0042 PB - Elsevier DO - 10.1016/j.isci.2026.116930 UR - https://doi.org/10.1016/j.isci.2026.116930 LA - en ER -

CSL-JSON

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