Scn2a insufficiency alters spontaneous neuronal Ca2+ activity in somatosensory cortex during wakefulness

Melody Li; Mohamed Eltabbal; Hoang-Dai Tran; Bernd Kuhn

doi:10.1016/j.isci.2023.108138

Scn2a insufficiency alters spontaneous neuronal Ca²⁺ activity in somatosensory cortex during wakefulness

iScience. 2023 Oct 5;26(11):108138. doi: 10.1016/j.isci.2023.108138. eCollection 2023 Nov 17.

Authors

Melody Li¹, Mohamed Eltabbal¹, Hoang-Dai Tran¹, Bernd Kuhn¹

Affiliation

¹ Optical Neuroimaging Unit, Okinawa Institute of Science and Technology Graduate University (OIST), 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan.

Abstract

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 Ca²⁺ imaging and electrocorticography (ECoG) in awake mice showed that spontaneous Ca²⁺ 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.

Keywords: Cellular neuroscience; Molecular neuroscience.

Associated data

Dryad/10.5061/dryad.83bk3j9z2