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Record W4413802634 · doi:10.1101/2025.08.23.671929

Giant and Opposite Lithium Isotope Effects on Rat Hippocampus Synaptic Activity Revealed by Multi-Electrode Array Electrophysiology

2025· preprint· en· W4413802634 on OpenAlexaff
Khadijeh Esmaeilpour, Irina Bukhteeva, Brian Kendall, Michel J. P. Gingras, Zoya Leonenko, John G. Mielke

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldNeuroscience
TopicNeuroscience and Neuropharmacology Research
Canadian institutionsUniversity of Waterloo
FundersUniversity of California, Santa BarbaraIonis Pharmaceuticals
KeywordsNeuroscienceNeural facilitationElectrophysiologyLong-term potentiationExcitatory postsynaptic potentialLithium (medication)FacilitationNeurotransmissionHippocampusSynaptic plasticityChemistryPsychologyPsychiatryInhibitory postsynaptic potential

Abstract

fetched live from OpenAlex

INTRODUCTORY SUMMARY Lithium (Li) has been a frontline medication for the treatment of bipolar disorder for decades, but its mechanism of action remains poorly understood 1,2 . While clinically prescribed Li salts consist of a mixture of two stable isotopes, 6 Li and 7 Li, the neurobiological effects of each isotope are only beginning to receive attention. Recent theoretical proposals have suggested that the Li isotopes may exert unique effects in the brain, stemming from quantum phenomena linked to their distinct nuclear spin properties 3–5 . However, aside from earlier observations of isotope-dependent variations in animal behavior 6,7 , direct experimental evidence is lacking. We used multi-electrode array electrophysiology to probe field excitatory post-synaptic potentials (fEPSPs) in rat brain slices and demonstrated that 6 Li and 7 Li have large and opposite effects on synaptic transmission and lead to smaller, but still distinct, differences in synaptic plasticity, particularly, paired-pulse facilitation and the early stages of long-term potentiation. Our results provide direct experimental evidence that Li isotopes exert remarkably different neurological effects, while avoiding many of the interpretive challenges associated with behavioural studies. These findings lay the groundwork for future investigations of quantum phenomena in neuronal activity and promote the idea that Li isotopes are pharmacologically distinct agents.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.018
GPT teacher head0.273
Teacher spread0.255 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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