| First Author | Davatolhagh MF | Year | 2021 |
| Journal | Cell Rep | Volume | 34 |
| Issue | 8 | Pages | 108773 |
| PubMed ID | 33626349 | Mgi Jnum | J:312322 |
| Mgi Id | MGI:6714855 | Doi | 10.1016/j.celrep.2021.108773 |
| Citation | Davatolhagh MF, et al. (2021) Neurexin1 differentially regulates synaptic efficacy within striatal circuits. Cell Rep 34(8):108773 |
| abstractText | Mutations in genes essential for synaptic function, such as the presynaptic adhesion molecule Neurexin1alpha (Nrxn1alpha), are strongly implicated in neuropsychiatric pathophysiology. As the input nucleus of the basal ganglia, the striatum integrates diverse excitatory projections governing cognitive and motor control, and its impairment may represent a recurrent pathway to disease. Here, we test the functional relevance of Nrxn1alpha in striatal circuits by employing optogenetic-mediated afferent recruitment of dorsal prefrontal cortical (dPFC) and parafascicular thalamic connections onto dorsomedial striatal (DMS) spiny projection neurons (SPNs). For dPFC-DMS circuits, we find decreased synaptic strength specifically onto indirect pathway SPNs in both Nrxn1alpha(+/-) and Nrxn1alpha(-/-) mice, driven by reductions in neurotransmitter release. In contrast, thalamic excitatory inputs to DMS exhibit relatively normal excitatory synaptic strength despite changes in synaptic N-methyl-D-aspartate receptor (NMDAR) content. These findings suggest that dysregulation of Nrxn1alpha modulates striatal function in an input- and target-specific manner. |
