Schizophrenia-associated SAP97 mutations increase glutamatergic synapse strength in the dentate gyrus and impair contextual episodic memory in rats.-猫眼课题宝

与精神分裂症相关的SAP97突变增加了大鼠齿状回中谷氨酸能突触的强度，并损害了大鼠的情景记忆。

DOI：

10.1038/s41467-022-28430-5

发表时间：

2022-02-10

期刊：

Nature communications

影响因子：

16.6

通讯作者：

中科院分区：

综合性期刊1区

文献类型：

作者：

Kay Y;Tsan L;Davis EA;Tian C;Décarie-Spain L;Sadybekov A;Pushkin AN;Katritch V;Kanoski SE;Herring BE

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831576/

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.