Some genetic versions of autism, such as Dravet syndrome, caused by mutations in the voltage-gated sodium channel gene Scn1a, have been linked to reductions in inhibitory neurotransmission, but the extent to which this is also true for idiopathic forms of autism has been unclear. Now, Sung Han and colleagues show that dysfunctional inhibitory neurotransmission is responsible for social deficits in a nonsyndromic mouse model of autism (Neuron 81, 1282–1289, 2014).
The researchers carried out electrophysiological recordings from the hippocampus of BTBR mice, a model of idiopathic autism that displays many autistic-like behaviors such as dysfunctional social interactions and repetitive behaviors. They found reduced inhibitory neurotransmission in that brain region that could be restored with benzodiazepines, drugs that activate GABA receptors and are currently in clinical use to treat anxiety and epilepsy. The doses of benzodiazepines used to treat those disorders in humans can induce sedation as a side effect, but in these BTBR mice, even low, nonsedating doses could improve learning and social interactions. Conversely, treating two different lines of control mice that exhibit no autistic behaviors with drugs that reduce GABA receptor activity led to social deficits.
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