CoChat
Sign Up
Cited by 16Neuroscience of respiration and sleepNeuroscience and Neuropharmacology ResearchRespiratory and Cough-Related Research

Lactate ions induce synaptic plasticity to enhance output from the central respiratory network

Open access
Bueschke, Nikolaus, Amaral‐Silva, Lara, Hu, Min, Santin, Joseph M.·2021·The Journal of Physiology
DOI 10.1113/jp282062PMC PMC8696744
Open this paper in CoChat — free account

Abstract

Abstract Lactate ion sensing has emerged as a process that regulates ventilation during metabolic challenges. Most work has focused on peripheral sensing of lactate for the control of breathing. However, lactate also rises in the central nervous system (CNS) during disturbances to blood gas homeostasis and exercise. Using an amphibian model, we recently showed that lactate ions, independently of pH and pyruvate metabolism, act directly in the brainstem to increase respiratory‐related motor outflow. This response had a long washout time and corresponded with potentiated excitatory synaptic strength of respiratory motoneurons. Thus, we tested the hypothesis that lactate ions enhance respiratory output using cellular mechanisms associated with long‐term synaptic plasticity within motoneurons. In this study, we confirm that 2 mM sodium lactate, but not sodium pyruvate, increases respiratory motor output in brainstem‐spinal cord preparations, persisting for 2 h upon the removal of lactate. Lactate also led to prolonged increases in the amplitude of AMPA‐glutamate receptor (AMPAR) currents in individual motoneurons from brainstem slices. Both motor facilitation and AMPAR potentiation by lactate required classic effectors of synaptic plasticity, L‐type Ca 2+ channels and NMDA receptors, as part of the transduction process but did not correspond with increased expression of immediate‐early genes often associated with activity‐dependent neuronal plasticity. Altogether these results show that lactate ions enhance respiratory motor output by inducing conserved mechanisms of synaptic plasticity and suggest a new mechanism that may contribute to coupling ventilation to metabolic demands in vertebrates. Key points Lactate ions, independently of pH and metabolism, induce long‐term increases in respiratory‐related motor outflow in American bullfrogs. Lactate triggers a persistent increase in strength of AMPA‐glutamatergic synapses onto respiratory motor neurons. Long‐term plasticity of motor output and synaptic strength by lactate involves L‐type Ca 2+ channels and NMDA‐receptors as part of the transduction process. Enhanced AMPA receptor function in response to lactate in the intact network is causal for motor plasticity. In sum, well‐conserved synaptic plasticity mechanisms couple the brainstem lactate ion concentration to respiratory motor drive in vertebrates.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1113/jp282062

Cites

81 of 81 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The metabolic responses to perceived, but not unperceived, sensory stimulation could be enabling factors for learning and memory.

    “As such, the metabolic responses to perceived, but not unperceived, sensory stimulation could be enabling factors for learning and memory”

    From Perception is associated with the brain’s metabolic response to sensory stimulation (2022) · cites this paper as Bueschke et al., 2021

    The Discussion (page unavailable) reports that lactate enhances synaptic strength in the central respiratory network. Our copy does not address metabolic responses to perceived versus unperceived sensory stimulation or their role in learning and memory; searches for those terms found no relevant passage. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 82 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Halestrap AP. (2011). Monocarboxylic acid transport. Comprehensive physiology 3, 1611– 1643. 24265240

Cited by

Sorted by citations

Related

Authors
Bueschke, N., Amaral‐Silva, L., Hu, M., & Santin, J. M.
Affiliations
University of North Carolina at Greensboro (US)
Corresponding author
Santin, Joseph M.
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
2021-12
Volume
599
Issue
24
Pages
5485-5504
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jp282062
PMC
PMC8696744
OpenAlex
W3212518129
Cited by
16
References
82
Citations by year
2026: 2 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 3
FWCI
1.18
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (1r15ns112920-01a1)
  • National Institute of Neurological Disorders and Stroke (R15 NS112920)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory and Cough-Related Research
Keywords
lactate, synaptic plasticity, respiratory motoneurons, AMPA receptor potentiation, L-type calcium channels, NMDA receptor, motor output, sodium lactate, pyruvate, American bullfrog, activity-dependent plasticity
MeSH terms
Animals, Ions, Neuronal Plasticity, Synapses, Receptors, AMPA, Lactic Acid

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review