Whole-genome analysis of sporadic amyotrophic lateral sclerosis.

Background: Approximately 90% of persons with amyotrophic lateral sclerosis (ALS) have the sporadic form, which may be caused by the interaction of multiple environmental factors and previously unknown genes.

Methods: We performed a genomewide association analysis using 766,955 single-nucleotide polymorphisms (SNPs) found in 386 white patients with sporadic ALS and 542 neurologically normal white controls (the discovery series). Associations of SNPs with sporadic ALS were confirmed in two independent replication populations: replication series 1, with 766 case patients with the disease and 750 neurologically normal controls, and replication series 2, with 135 case patients and 275 controls.

Visually driven regulation of intrinsic neuronal excitability improves stimulus detection in vivo.

Neurons adapt their electrophysiological properties to maintain stable levels of electrical excitability when faced with a constantly changing environment. We find that exposing freely swimming Xenopus tadpoles to 4-5 hr of persistent visual stimulation increases the intrinsic excitability of optic tectal neurons. This increase is correlated with enhanced voltage-gated Na+ currents.