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
Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, 90089, USA.
Department of Biological Sciences, Human and Evolutionary Biology Section, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, 90089, USA.
Nat Commun. 2022 Feb 10;13(1):798. doi: 10.1038/s41467-022-28430-5.
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.
假定的谷氨酸能突触支架蛋白SAP97的突变与人类精神分裂症的发生有关。然而，SAP97在突触调节中的作用尚不清楚。在这里，我们表明SAP97在齿状回颗粒神经元的树突中表达，但在其他海马神经元的树突中不表达。与精神分裂症相关的SAP97扰动不影响CA1锥体神经元突触功能。相反，这些扰动会使颗粒神经元中的谷氨酸能神经传递显著增强，这可归因于含GluA1的AMPA受体从突触周围释放到穿通通路突触的突触后致密物中。此外，抑制齿状回中的SAP97功能足以损害情境性情景记忆。总之，我们的结果确定了齿状回中一种细胞类型特异性的突触调节机制，该机制一旦被破坏，就会损害大鼠的情境信息处理。
