haploinsufficient mice display a spectrum of phenotypes affecting anxiety, sociability, memory flexibility and ampakine CX516 rescues their hyperactivity.

Background: Mutations of the gene encoding a voltage-gated sodium channel alpha-II subunit Nav1.2 are associated with neurological disorders such as epilepsy, autism spectrum disorders, intellectual disability, and schizophrenia. However, causal relationships and pathogenic mechanisms underlying these neurological defects, especially social and psychiatric features, remain to be elucidated.

Nav1.2 haplodeficiency in excitatory neurons causes absence-like seizures in mice.

Mutations in the gene encoding a voltage-gated sodium channel Nav1.2 are associated with epilepsies, intellectual disability, and autism. gain-of-function mutations cause early-onset severe epilepsies, while loss-of-function mutations cause autism with milder and/or later-onset epilepsies.

Altered hippocampal replay is associated with memory impairment in mice heterozygous for the Scn2a gene.

An accumulating body of experimental evidence has implicated hippocampal replay occurring within sharp wave ripples (SPW-Rs) as crucial for learning and memory in healthy subjects. This raises speculation that neurological disorders impairing memory disrupt either SPW-Rs or their underlying neuronal activity. We report that mice heterozygous for the gene Scn2a, a site of frequent de novo mutations in humans with intellectual disability, displayed impaired spatial memory.

Tetanus neurotoxin: conformational plasticity as an adaptive strategy.

Tetanus neurotoxin (TeNT) secreted by is the causative agent of the spastic paralysis distinctive of human tetanus. TeNT is structurally related to the family of botulinum neurotoxins (BoNTs) produced by that cause flaccid paralysis by disabling synaptic exocytosis at peripheral cholinergic neurons. By contrast, TeNT targets the central nervous system (CNS) by hijacking receptors for neurotrophic factors to enter peripheral neurons thereby being sorted into non‐acidifying endosomes, trafficking via retrograde axonal transport organelles, and entering spinal inhibitory interneurons after transcytosis (Fig 1A).

LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength.

The volume-regulated anion channel (VRAC) is activated when a cell swells, and it plays a central role in maintaining cell volume in response to osmotic challenges. SWELL1 (LRRC8A) was recently identified as an essential component of VRAC. However, the identity of the pore-forming subunits of VRAC and how the channel is gated by cell swelling are unknown.