---
title: "CA3 Pyramidal Neuron Activation Function Supports Stable Memory Recall"
id: "biorxiv-17-the-activation-function-of-ca3-pyramidal-neurons-is-optimal-for-the-stable"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-17-the-activation-function-of-ca3-pyramidal-neurons-is-optimal-for-the-stable"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.17.752025v1?rss=1"
published_at: "2026-09-20T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# CA3 Pyramidal Neuron Activation Function Supports Stable Memory Recall
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-17-the-activation-function-of-ca3-pyramidal-neurons-is-optimal-for-the-stable
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.17.752025v1?rss=1)
- **Published At:** 2026-09-20T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The hippocampal CA3 region is theorized to retrieve stored distributed activity patterns via recurrent connections; how single-neuron physiology contributes to this function was previously unresolved. - The authors performed a mathematical analysis of a canonical recurrent neural network model of CA3 and derived three experimentally testable predictions for circuits that support stable memory recall. - Two predictions—elevated **intrinsic excitability** of pyramidal cells and **inhibition-dominated recurrent connections**—align with prior experimental findings. - The third prediction, tested here, is that neuronal **activation functions** should have an exponent slightly greater than 1 to optimize stable recall. - To test this, the team recorded intracellular voltage traces from 49 CA3 pyramidal neurons in behaving mice and fit multiple parametric activation models to those traces. - Statistical model comparison of the fits yielded an average activation exponent slightly above 1, confirming the theoretical prediction, while revealing substantial cell-to-cell heterogeneity. - The authors further analyzed activation exponents estimated from 133 additional cells reported in two prior studies and found estimates consistent with their new recordings. - Overall, the findings indicate that properties of CA3 pyramidal neurons are tuned to support reliable memory recall down to single-neuron activation characteristics. - The study declares no competing interests and acknowledges funding from the Wellcome Trust and the Human Frontiers Science Programme.
## Clinical Analysis & Structured Key Points
The activation function of CA3 pyramidal neurons is optimal for the stable recall of memory patterns | bioRxiv Skip to main content New Results The activation function of CA3 pyramidal neurons is optimal for the stable recall of memory patterns View ORCID Profile Uri Cohen , View ORCID Profile Maria Magdalena Picher , View ORCID Profile Andrea Navas-Olive , View ORCID Profile Máté Lengyel doi: https://doi.org/10.64898/2026.09.17.752025 Uri Cohen 1 University of Cambridge, UK; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Uri Cohen For correspondence: uc231{at}cam.ac.uk Maria Magdalena Picher 2 Institute of Science and Technology Austria, Austria Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Maria Magdalena Picher Andrea Navas-Olive 2 Institute of Science and Technology Austria, Austria Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Andrea Navas-Olive Máté Lengyel 1 University of Cambridge, UK; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Máté Lengyel Abstract Info/History Metrics Preview PDF Abstract Hippocampal area CA3 is widely believed to serve a core memory function: retrieving distributed patterns of neural activity that were previously stored in the recurrent connections between neurons. However, it remains unknown how the physiological properties of individual neurons contribute to this function. Here, we present a mathematical analysis of a canonical recurrent neural network model of CA3. Our analysis provides three main, experimentally testable predictions for recurrent circuits performing stable memory recall. Two of these predictions, that pyramidal cells should be characterized by elevated intrinsic excitability and by inhibition-dominated recurrent connections, are consistent with previous experimental findings. We thus focused on testing the third prediction: that neuronal activation functions have an exponent slightly above $1$. For this, we performed \textit{in vivo} intracellular recordings of 49 pyramidal neurons from the CA3 area of behaving mice. Fitting a range of parametric models to these voltage traces and performing statistical model comparison revealed an average neural activation exponent slightly above $1$, confirming our theoretical predictions, with substantial heterogeneity across cells, which remains to be accounted for by the theory. An analysis of 133 further cells from two other previous studies provided neural activation exponent estimates highly consistent with those we found in our data. Our results suggest that the properties of hippocampal CA3 area are tuned to support reliable memory recall even at the level of single neurons. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared Wellcome Trust, https://ror.org/029chgv08 , 212262/Z/18/Z Human Frontiers Science Programme , RGP0044/2018 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license . Back to top Previous Next Posted September 20, 2026. Download PDF Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following The activation function of CA3 pyramidal neurons is optimal for the stable recall of memory patterns Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share The activation function of CA3 pyramidal neurons is optimal for the stable recall of memory patterns Uri Cohen , Maria Magdalena Picher , Andrea Navas-Olive , Máté Lengyel bioRxiv 2026.09.17.752025; doi: https://doi.org/10.64898/2026.09.17.752025 Share This Article: Copy Citation Tools The activation function of CA3 pyramidal neurons is optimal for the stable recall of memory patterns Uri Cohen , Maria Magdalena Picher , Andrea Navas-Olive , Máté Lengyel bioRxiv 2026.09.17.752025; doi: https://doi.org/10.64898/2026.09.17.752025 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Neuroscience Subject Areas All Articles Animal Behavior and Cognition (8013) Biochemistry (18739) Bioengineering (14888) Bioinformatics (44418) Biophysics (22599) Cancer Biology (19723) Cell Biology (26899) Clinical Trials (138) Developmental Biology (13965) Ecology (21005) Epidemiology (2067) Evolutionary Biology (25455) Genetics (16166) Genomics (23507) Immunology (18705) Microbiology (42503) Molecular Biology (18059) Neuroscience (93451) Paleontology (700) Pathology (2977) Pharmacology and Toxicology (5095) Physiology (8114) Plant Biology (15999) Scientific Communication and Education (2095) Synthetic Biology (4560) Systems Biology (10235) Zoology (2391)
## Related Clinical Research

- [Correction: Data-driven framework for modeling the dendritic spine continuum — funding and corresp](https://medichelpline.com/clinical-feed/plos-one-1-correction-a-data-driven-framework-for-modeling-the-dendritic-spine-continuum.md)
- [Serum Na–Cl Difference as a Noninvasive Screen for CO2 Retention in ALS](https://medichelpline.com/clinical-feed/plos-one-2-serum-na-cl-value-from-routine-blood-tests-reflects-co-2-retention-in.md)
- [Periodised Power Training (POWER) Pilot RCT Protocol for Chronic Stroke Recovery](https://medichelpline.com/clinical-feed/bmj-open-9-periodised-power-training-in-community-dwelling-adults-with-chronic-stroke-a.md)
- [Night-onset Stroke Linked to Worse 3‑Month Outcomes After Reperfusion Therapy](https://medichelpline.com/clinical-feed/bmj-open-19-association-of-time-of-day-at-stroke-onset-with-functional-outcomes-after.md)
- [Excitatory progenitor diversification in the rhombic lip drives evolution of new cerebellar nuclei](https://medichelpline.com/clinical-feed/biorxiv-18-evolution-of-new-cerebellar-nuclei-by-excitatory-progenitor-diversification-in.md)

## Navigation
- [← Back to Neurology Feed](https://medichelpline.com/clinical-feed/neurology.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.