Enhanced Social Dominance and Altered Neuronal Excitability in the Prefrontal Cortex of Male KCC2b Mutant Mice.
Allison M J Anacker, Jacqueline T Moran, Sara Santarelli and 7 others
PMID 30977597WHAT IT FOUND
In male mice with reduced KCC2, most autism-related behavior tests were unchanged, including the primary anxiety measure.
They won more tube-test matches, and prefrontal neurons had larger excitatory signals, not inhibitory signals.
Key findings
01Heterozygous KCC2 mice showed enhanced social dominance in the tube test, winning more bouts than wild-type littermates.
02No significant genotype differences were found in anxiety-like behavior, locomotor activity, home-cage behavior, repetitive behavior, sociability, reciprocal social behavior, or ultrasonic vocalizations.
03In prefrontal cortex neurons, miniature excitatory synaptic current amplitude was increased in heterozygous mice, while miniature inhibitory synaptic currents were not significantly changed.
STILL TO COME
How it was doneWhat they found
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What it does not show
This is a mouse study, not a human clinical trial. The behavior battery was tested in 33 mice, and three heterozygous mice showed seizure-like movements, with one dying before social testing. Only male mice were used for behavior testing. The positive behavioral finding was limited to the tube test, which does not directly correspond to social deficits commonly observed in people with autism. The KCC2 inhibitor tested in slices has poor drug metabolism and pharmacokinetic profiling and is unlikely to reach the brain after peripheral administration. Behavior tests were done after the presumed GABA switch and at young adulthood, so effects at other developmental stages were not assessed.
Declared interests
The article is listed as supported by NIH and non-U.S. government research funding. No conflict-of-interest declaration is included in the article text.
The easy way to misread this
Do not read this as evidence that changing KCC2 would improve autism symptoms in people. The mice had a genetic reduction in KCC2, and most autism-related behavior tests were unchanged. The positive finding was increased dominance in a mouse tube test.