| First Author | Li M | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 11 | Pages | 108138 |
| PubMed ID | 37876801 | Mgi Jnum | J:342024 |
| Mgi Id | MGI:7544651 | Doi | 10.1016/j.isci.2023.108138 |
| Citation | Li M, et al. (2023) Scn2a insufficiency alters spontaneous neuronal Ca(2+) activity in somatosensory cortex during wakefulness. iScience 26(11):108138 |
| abstractText | SCN2A protein-truncating variants (PTV) can result in neurological disorders such as autism spectrum disorder and intellectual disability, but they are less likely to cause epilepsy in comparison to missense variants. While in vitro studies showed PTV reduce action potential firing, consequences at in vivo network level remain elusive. Here, we generated a mouse model of Scn2a insufficiency using antisense oligonucleotides (Scn2a ASO mice), which recapitulated key clinical feature of SCN2A PTV disorders. Simultaneous two-photon Ca(2+) imaging and electrocorticography (ECoG) in awake mice showed that spontaneous Ca(2+) transients in somatosensory cortical neurons, as well as their pairwise co-activities were generally decreased in Scn2a ASO mice during spontaneous awake state and induced seizure state. The reduction of neuronal activities and paired co-activity are mechanisms associated with motor, social and cognitive deficits observed in our mouse model of severe Scn2a insufficiency, indicating these are likely mechanisms driving SCN2A PTV pathology. |
