Zoicas I, Sucu B, Kornhuber J, Fejtová A (2026)
Publication Type: Journal article
Publication year: 2026
Book Volume: 222
Article Number: 107362
DOI: 10.1016/j.nbd.2026.107362
Bassoon is a large presynaptic scaffold protein expressed at excitatory and inhibitory synapses, and mutations in BSN are linked to neuropsychiatric and neurodevelopmental disorders. To investigate its role in telencephalic excitatory circuits, we generated a conditional mouse model (BsnNEXcKO) in which Bassoon is selectively deleted from glutamatergic neurons of the neocortex and limbic system while being preserved in neurogenic lineage and in a subset of granule cells of the dentate gyrus in adulthood. Learning and memory were assessed using aversive and non-aversive paradigms, including social tasks and similarly-designed non-social control tasks. In non-aversive paradigms, such as social and object discrimination, BsnNEXcKO mice of both sexes exhibited enhanced retention of social and non-social memory. In aversive paradigms, including social fear conditioning and non-social (cued and contextual) fear conditioning, fear learning was unaffected. However, BsnNEXcKO mice displayed increased expression of social, cued and contextual fear, reflecting enhanced stability of conditioned fear memories. Notably, extinction of social fear was impaired in BsnNEXcKO mice, indicating a reduced capacity to update or relearn associations. This pattern points to deficits in cognitive flexibility, a process essential for gradual suppression of previously-learned fear responses. In parallel, BsnNEXcKO mice exhibited increased adult hippocampal neurogenesis caused by cell non-autonomous mechanisms, consistent with a role in hippocampus-dependent learning. These findings suggest that the loss of Bassoon from telencephalic excitatory presynaptic terminals strengthens memory stability in social and non-social tasks across aversive and non-aversive contexts, while impairing cognitive flexibility, particularly in situations requiring suppression or modification of previously-learned aversive associations.
APA:
Zoicas, I., Sucu, B., Kornhuber, J., & Fejtová, A. (2026). Loss of Bassoon in telencephalic excitatory neurons stabilizes non-aversive memories and strengthens aversive associations in social and non-social contexts. Neurobiology of Disease, 222. https://doi.org/10.1016/j.nbd.2026.107362
MLA:
Zoicas, Iulia, et al. "Loss of Bassoon in telencephalic excitatory neurons stabilizes non-aversive memories and strengthens aversive associations in social and non-social contexts." Neurobiology of Disease 222 (2026).
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