Phenotypic characterization of nonsocial behavioral impairment in neurexin 1α knockout rats.
Abstract
Neurexins are neuronal presynaptic proteins that play a key role in mediation of synapse formation. Heterozygous partial deletions in the neurexin-1 gene (NRXN1, 2p16.3) have been observed in autism spectrum disorder (ASD) patients. NRXN1-α knockout (KO) mice present behavioral impairments that resemble some of the core ASD symptoms of social impairment and inflexibility/stereotypy. At present, a thorough assessment of cognitive function has yet to be completed. Rats, containing a biallelic deletion of the NRNX1-α gene on a Sprague Dawley background were compared to littermate wild types across a range of tasks designed to test functional domains disrupted in ASD and other neurodevelopmental disorders, including sensory perception (prepulse inhibition), attention (latent inhibition), associative learning (instrumental and Pavlovian conditioning), and memory (rewarded alternation T maze and spatial discrimination). NRXN1α KO rats were found to present with large and persistent nonsocial deficits, including hyperactivity, deficits in simple instrumental learning, latent inhibition, and spatial-dependent learning. No deficit in sensorimotor gating was observed, despite the presence of an exaggerated startle response. Although KO animals were also able to learn a simple Pavlovian conditioning discrimination, they did display impaired latent inhibition. The presence of pronounced impairments in several domains in NRXN1α KO rats clearly suggests that nonsocial cognitive deficits ca…
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Previous studies with nrxn1-deficient rats have shown profound impairments in attention and cognitive capacities, as well as hyperactivity.
“Previous studies with nrxn1-deficient rats have shown profound impairments in attention and cognitive capacities, as well as hyperactivity (Esclassan et al. 2015)”
From Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia (2025) · cites this paper as Esclassan et al. 2015
The profound hyperactivity of the nrxn1-KO rats in a novel environment may have interfered with the expression of social play in the Kight study.
“In addition, the profound hyperactivity of the nrxn1-KO rats in a novel environment (Esclassan et al. 2015; Kight et al. 2021; present study) may have interfered with the expression of social play in the Kight study”
From Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia (2025) · cites this paper as Esclassan et al. 2015
nrxn1-KO rats were hyperactive in the amphetamine experiment.
“In this experiment, nrxn1-KO rats were hyperactive, as was found previously (Esclassan et al. 2015; Kight et al. 2021)”
From Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia (2025) · cites this paper as Esclassan et al. 2015
nrxn1-KO rats show marked locomotor hyperactivity.
“we also observed marked locomotor hyperactivity in the nrxn1-KO rats, consistent with previous studies (Esclassan et al. 2015; Kight et al. 2021).”
From Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia (2025) · cites this paper as Esclassan et al. 2015
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Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits
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Convergence of Sex Differences and the Neuroimmune System in Autism Spectrum Disorder
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An intra-amygdala circuit specifically regulates social fear learning
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Social behavior in prepubertal neurexin 1α deficient rats: A model of neurodevelopmental disorders.
Kight, K. E., Argue, K. J., Bumgardner, J. G., Bardhi, K., Waddell, J., & McCarthy, M. M. (2021) · Behavioral Neuroscience · doi:10.1037/bne0000482 · Cited by 17 · see citing works
Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia
Achterberg, E. J. M., Biemans, B., & Vanderschuren, L. J. M. J. (2025) · Psychopharmacology · doi:10.1007/s00213-024-06559-z · Cited by 9 · see citing works
“Previous studies with nrxn1-deficient rats have shown profound impairments in attention and cognitive capacities, as well as hyperactivity (Esclassan et al. 2015), altered patterns of social interest (Twining et al. 2017), sex-specific deficits in ultrasonic vocalizations and social play, but…”
Influential
- Authors
- Esclassan, F., Francois, J., Phillips, K. G., Loomis, S., & Gilmour, G.
- Venue
- Behavioral Neuroscience
- Published
- 2015
- Volume
- 129
- Issue
- 1
- Pages
- 74-85
- ISSN
- 0735-7044 (ISSN-L)
- 1939-0084
- OpenAlex
- W2039666355
- Cited by
- 52
- References
- 7
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 10 · 2020: 4 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 6
- FWCI
- 2.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioral Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- autism spectrum disorder, social dysfunction, hyperactivity, latent inhibition, prepulse inhibition, sensorimotor gating, startle response, operant conditioning, classical conditioning, spatial learning, memory, cognitive impairment, animal models of autism
- MeSH terms
- Animals, Association Learning, Attention, Behavior, Animal, Child Development Disorders, Pervasive, Disease Models, Animal, Female, Glycoproteins, Male, Neuropeptides, Phenotype, Rats, Sprague-Dawley, Gene Deletion, Rats, Sensory Gating, Rats, Transgenic, Gene Knockout Techniques, Prepulse Inhibition, Spatial Memory
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