Spiking cell: Neurons from mice with an autism-linked mutation show excess bursts of activity early in development.

Newborn mice with an autism-linked mutation in neuroligin-3 (NLGN3) have abnormal brain chemistry, according to a study published 4 June in Frontiers in Cellular Neuroscience¹.

The results suggest that this mutation may alter brain signaling starting early in development.

NLGN3 stabilizes connections between neurons, or synapses. It was first linked to autism in 2003, when researchers found a single mutation in the gene in two brothers with autism. Some mice with this mutation show social deficits reminiscent of autism², but others have more typical social behavior³.

A 2012 study found that in mice with the mutation, synapses don’t strengthen as well in response to experience — a process that underlies learning and memory — as they do in controls.

The new study is the first to examine the brains of mice with this mutation immediately after birth, which is developmentally equivalent to the third trimester of pregnancy in people. At this age, gamma aminobutyric-acid (GABA), a chemical messenger that typically dampens neuronal activity, instead activates brain signals. These GABA-induced signals may help establish early synapse formation.

Newborn mice with the NLGN3 mutation have more of these waves of activity, called giant depolarizing potentials, than controls do, the study found. This is because their neurons release excess GABA into synapses, the findings suggest.

The mice do not show a corresponding boost in activity generated by another type of chemical messenger, glutamate, which typically activates brain signals, the study found.

The results suggest that an altered balance between these two types of brain signals early in development may underlie autism.

References:

1: Pizzarelli R. and E. Cherubini Front. Cell Neurosci. 7, 85 (2013) PubMed

2: Tabuchi K. et al. Science 318, 71-76 (2007) PubMed

3:  Chadman K.K. et al. Autism Res. 1, 147-158 (2008) PubMed