| First Author | Amalyan S | Year | 2022 |
| Journal | Cell Rep | Volume | 40 |
| Issue | 1 | Pages | 111043 |
| PubMed ID | 35793625 | Mgi Jnum | J:342095 |
| Mgi Id | MGI:7314080 | Doi | 10.1016/j.celrep.2022.111043 |
| Citation | Amalyan S, et al. (2022) Enhanced motor cortex output and disinhibition in asymptomatic female mice with C9orf72 genetic expansion. Cell Rep 40(1):111043 |
| abstractText | Information and action coding by cortical circuits relies on a balanced dialogue between excitation and inhibition. Circuit hyperexcitability is considered a potential pathophysiological mechanism in various brain disorders, but the underlying deficits, especially at early disease stages, remain largely unknown. We report that asymptomatic female mice carrying the chromosome 9 open reading frame 72 (C9orf72) repeat expansion, which represents a high-prevalence genetic abnormality for human amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) spectrum disorder, exhibit abnormal motor cortex output. The number of primary motor cortex (M1) layer 5 pyramidal neurons is reduced in asymptomatic mice, with the surviving neurons receiving a decreased inhibitory drive that results in a higher M1 output, specifically during high-speed animal locomotion. Importantly, using deep-learning algorithms revealed that speed-dependent M1 output predicts the likelihood of C9orf72 genetic expansion. Our data link early circuit abnormalities with a gene mutation in asymptomatic ALS/FTLD carriers. |
