---
title: "Neuron type–specific Bassoon loss in mice links interneuron deficits to schizophrenia-like behavio"
id: "biorxiv-8-dissection-of-neuropsychiatric-relevant-behavioral-and-structural-phenotypes"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-8-dissection-of-neuropsychiatric-relevant-behavioral-and-structural-phenotypes"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.09.757973v1?rss=1"
published_at: "2026-10-16T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Neuron type–specific Bassoon loss in mice links interneuron deficits to schizophrenia-like behavio
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-8-dissection-of-neuropsychiatric-relevant-behavioral-and-structural-phenotypes
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.09.757973v1?rss=1)
- **Published At:** 2026-10-16T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Investigators used conditional knockout mice to remove the **Bassoon** (BSN) presynaptic protein selectively from three neuronal populations: inhibitory interneurons (BsnDlx5/6cKO), forebrain excitatory neurons (BsnEmx1cKO), and dopaminergic neurons (BsnDATcKO). - The team assessed sensorimotor gating using prepulse inhibition and evaluated fear versus safety discrimination with a conditioned fear/safety learning paradigm; anxiety-like behavior was measured in the light/dark box. - Data indicated impaired sensory gating in both the interneuron-targeted (BsnDlx5/6cKO) and excitatory-targeted (BsnEmx1cKO) lines, while the dopaminergic-targeted (BsnDATcKO) line did not show this deficit. - BsnDlx5/6cKO mice failed to discriminate conditioned fear from safety—an impairment frequently observed in people with schizophrenia; by contrast, BsnDATcKO mice showed enhanced discrimination. - All three conditional knockout strains displayed increased anxiety-like behavior in the light/dark box. - Structural MRI revealed increased brain volumes in BsnDlx5/6cKO and BsnEmx1cKO mice, with the largest changes noted in the **hippocampus** and **cortex**. - Authors linked their findings to prior reports that BsnDlx5/6cKO mice also exhibit autistic-like behaviors, altered hippocampal network activity, and epilepsy, suggesting interneuron Bassoon loss may contribute to neurodevelopmental and neuropsychiatric phenotypes. - The article is a preprint and has not undergone peer review; the source did not report detailed experimental parameters (for example, exact behavioral protocols, sample sizes, or MRI acquisition parameters) in the abstract text provided here.
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Kreutzmann, [ View ORCID Profile](http://orcid.org/0000-0003-1157-714X)Frank Angenstein, [ View ORCID Profile](http://orcid.org/0000-0002-1815-4409)Anna Fejtova, [ View ORCID Profile](http://orcid.org/0000-0003-4285-7507)Oliver Stork, [ View ORCID Profile](http://orcid.org/0000-0001-9377-7414)Eckart D. Gundelfinger, [ View ORCID Profile](http://orcid.org/0000-0002-3451-1226)Markus Fendt, [ View ORCID Profile](http://orcid.org/0000-0002-6743-8627)Anil Annamneedi doi: https://doi.org/10.64898/2026.10.09.757973 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. Judith C. Kreutzmann 1 Institute for Pharmacology & Toxicology, Medical Faculty, Otto-von-Guericke University Magdeburg, 39118 Magdeburg, Germany; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Judith%2BC.%2BKreutzmann%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Kreutzmann%20JC&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJudith%2BC.%2BKreutzmann%2B) * [ORCID record for Judith C. Kreutzmann](http://orcid.org/0000-0003-0180-3449 "Open in new tab") Frank Angenstein 2 Functional Neuroimaging Group, Deutsches Zentrum fur Neurodegenerative Erkrankungen (DZNE), 39120 Magdeburg, Germany; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Frank%2BAngenstein%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Angenstein%20F&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AFrank%2BAngenstein%2B) * [ORCID record for Frank Angenstein](http://orcid.org/0000-0003-1157-714X "Open in new tab") Anna Fejtova 3 Department of Psychiatry and Psychotherapy, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nurnberg, 91054 Erlangen, Germany; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Anna%2BFejtova%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Fejtova%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAnna%2BFejtova%2B) * [ORCID record for Anna Fejtova](http://orcid.org/0000-0002-1815-4409 "Open in new tab") Oliver Stork 4 Institute of Biology, Otto-von-Guericke University Magdeburg; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Oliver%2BStork%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Stork%20O&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AOliver%2BStork%2B) * [ORCID record for Oliver Stork](http://orcid.org/0000-0003-4285-7507 "Open in new tab") Eckart D. Gundelfinger 1 Institute for Pharmacology & Toxicology, Medical Faculty, Otto-von-Guericke University Magdeburg, 39118 Magdeburg, Germany; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Eckart%2BD.%2BGundelfinger%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Gundelfinger%20ED&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AEckart%2BD.%2BGundelfinger%2B) * [ORCID record for Eckart D. Gundelfinger](http://orcid.org/0000-0001-9377-7414 "Open in new tab") Markus Fendt 1 Institute for Pharmacology & Toxicology, Medical Faculty, Otto-von-Guericke University Magdeburg, 39118 Magdeburg, Germany; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Markus%2BFendt%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Fendt%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMarkus%2BFendt%2B) * [ORCID record for Markus Fendt](http://orcid.org/0000-0002-3451-1226 "Open in new tab") Anil Annamneedi 5 Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany; School of Technology, Sai University, OMR, 603104 Paiyanur, Chennai, India * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Anil%2BAnnamneedi%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Annamneedi%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAnil%2BAnnamneedi%2B) * [ORCID record for Anil Annamneedi](http://orcid.org/0000-0002-6743-8627 "Open in new tab") * For correspondence: anil.a@saiuniversity.edu.in * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.09.757973v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5875874/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.09.757973v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5875874/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.09.757973v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5875874/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.10.09.757973v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5875874/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.09.757973v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5875874/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Rare pathogenic mutations in the human BSN gene, which encodes the presynaptic cytomatrix protein Bassoon-a key organizer of the neurotransmitter release apparatus have been linked to neuropsychiatric conditions including schizophrenia. Here we began to dissect the potential contribution of Bsn deficiency in distinct populations of mouse (fore)brain neurons on behavioral and anatomical alterations resembling schizophrenia-like phenotypes. To this end, conditional knockout mice lacking Bassoon in subsets of inhibitory synapses (BsnDlx5/6cKO), in forebrain excitatory synapses (BsnEmx1cKO), or at dopaminergic release sites (BsnDATcKO) were generated. The mice were assessed using prepulse inhibition, a paradigm that models sensorimotor gating, which is often impaired in schizophrenia, and a fear/safety learning paradigm. Further, anxiety-related behaviors were evaluated and magnetic resonance imaging (MRI) was performed to assess anatomical brain alterations. Our data reveal synapse-specific effects of the Bassoon deficiency. Sensory gating deficits were observed in both BsnDlx5/6cKO and BsnEmx1cKO mice. BsnDlx5/6cKO mice further demonstrated impaired discrimination between conditioned fear and safety-a condition frequently observed in individuals with schizophrenia. By contrast, BsnDATcKO mice displayed enhanced discrimination between conditioned fear and safety. All mouse strains showed elevated anxiety-like behavior in the light/dark box. Structural MRI revealed increased brain volumes in BsnDlx5/6cKO and BsnEmx1cKO mice, with the most pronounced changes in the hippocampus and cortex. Previous studies have shown that BsnDlx5/6cKO mice display autistic-like behaviors, altered hippocampal network activity and epilepsy. Our findings support the notion that deficits in Bsn-mediated functions, particularly in interneurons, may contribute to the etiology of neurodevelopmental and neuropsychiatric conditions. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared Deutsche Forschungsgemeinschaft, DFG-CRC 779, 36555331, SFB1436, 362321501/RTG 2413, 516641042 European Fonds für Regionale Entwicklung, ZS/2016/04/78113 Svenska Sällskapet för Medicinsk Forskning, PG-23-0400 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. [Donate to openRxiv ](https://www.zeffy.com/en-US/donation-form/donate-to-make-a-difference-10981) [ Back to top](https://www.biorxiv.org/content/10.64898/2026.10.09.757973v1?rss=1#page) [ Previous](https://www.biorxiv.org/content/10.64898/2026.10.09.758070v1 "Oral Bacterial Translocation Promotes Lung Dysbiosis and Infection Risk after Spinal Cord Injury") Posted October 16, 2026. [ Download PDF](https://www.biorxiv.org/content/10.64898/2026.10.09.757973v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/16/2026.10.09.757973.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.10.09.757973v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Dissection of neuropsychiatric-relevant behavioral and structural phenotypes utilizing neuron type-specific ablation of the Bassoon gene in mice Judith C. Kreutzmann, Frank Angenstein, Anna Fejtova, Oliver Stork, Eckart D. Gundelfinger, Markus Fendt, Anil Annamneedi bioRxiv 2026.10.09.757973; doi: https://doi.org/10.64898/2026.10.09.757973 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. Share This Article: Copy [![Twitter logo](https://www.biorxiv.org/sites/all/modules/highwire/highwire/images/twitter.png)](https://www.biorxiv.org/highwire_log/share/twitter?link=http%3A%2F%2Ftwitter.com%2Fshare%3Furl%3Dhttps%253A%2F%2Fwww.biorxiv.org%2Fcontent%2F10.64898%2F2026.10.09.757973v1%26text%3DDissection%2520of%2520neuropsychiatric-relevant%2520behavioral%2520and%2520structural%2520phenotypes%2520utilizing%2520neuron%2520type-specific%2520ablation%2520of%2520the%2520Bassoon%2520gene%2520in%2520mice "Share this on Twitter") [![Facebook logo](https://www.biorxiv.org/sites/all/modules/highwire/highwire/images/fb-blue.png)](https://www.biorxiv.org/highwire_log/share/facebo
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