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- Title
Schizophrenia-associated SAP97 mutations increase glutamatergic synapse strength in the dentate gyrus and impair contextual episodic memory in rats.
- Authors
Kay, Yuni; Tsan, Linda; Davis, Elizabeth A.; Tian, Chen; Décarie-Spain, Léa; Sadybekov, Anastasiia; Pushkin, Anna N.; Katritch, Vsevolod; Kanoski, Scott E.; Herring, Bruce E.
- Abstract
Mutations in the putative glutamatergic synapse scaffolding protein SAP97 are associated with the development of schizophrenia in humans. However, the role of SAP97 in synaptic regulation is unclear. Here we show that SAP97 is expressed in the dendrites of granule neurons in the dentate gyrus but not in the dendrites of other hippocampal neurons. Schizophrenia-related perturbations of SAP97 did not affect CA1 pyramidal neuron synapse function. Conversely, these perturbations produce dramatic augmentation of glutamatergic neurotransmission in granule neurons that can be attributed to a release of perisynaptic GluA1-containing AMPA receptors into the postsynaptic densities of perforant pathway synapses. Furthermore, inhibiting SAP97 function in the dentate gyrus was sufficient to impair contextual episodic memory. Together, our results identify a cell-type-specific synaptic regulatory mechanism in the dentate gyrus that, when disrupted, impairs contextual information processing in rats. The effects of SAP97 mutations associated with schizophrenia on synaptic function are unclear. Here, the authors show that schizophrenia-related SAP97 mutations enhance glutamatergic synapse strength in the dentate gyrus, impairing contextual episodic memory in rats.
- Subjects
DENTATE gyrus; EPISODIC memory; PYRAMIDAL neurons; AMPA receptors; RATS; SYNAPSES; NEURAL transmission
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-28430-5