Imbalance of flight-freeze responses and their cellular correlates in the Nlgn3-/y rat model of autism.
Natasha J Anstey, Vijayakumar Kapgal, Shashank Tiwari and 16 others
PMID 35850732WHAT IT FOUND
Rats lacking the NLGN3 protein show less freezing but more escape when afraid.
This isn't due to poor memory or pain sensitivity, but a brain circuit bias toward flight over freeze. It highlights that reduced freezing in autism models may reflect altered fear expression, not absent fear.
Key findings
01Nlgn3-deficient rats exhibit reduced classic freezing but increased escape and jumping behaviors in response to fear stimuli, indicating a shift in fear expression rather than impaired fear learning.
02Neurons in the dorsal periaqueductal grey (dPAG), a region controlling flight responses, are hyperexcitable in Nlgn3-deficient rats, while ventral PAG neurons remain normal.
03Direct electrical stimulation of the dPAG triggers flight responses in a significantly higher percentage of Nlgn3-deficient rats compared to controls, confirming a lowered threshold for escape behavior.
STILL TO COME
How it was doneWhat they found
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What it does not show
The study uses a rat model of autism; findings may not translate directly to human behavior or physiology. The precise cell types within the heterogeneous dorsal PAG responsible for the hyperexcitability were not identified. Fear responses were tested primarily using foot-shock; other fear-evoking stimuli like visual looming were not assessed. Behavioral phenotypes were examined in young adult animals, not during early development when symptoms typically emerge in humans. The biological relevance of the observed shorter duration of event-related potentials in the PAG is unclear.
Declared interests
Funded by the Simons Foundation Autism Research Initiative, the Medical Research Council, and the Department of Biotechnology Government of India.
The easy way to misread this
Do not interpret the reduced freezing behavior in these rats as a lack of fear or impaired memory. The study shows these animals still learn the association between the tone and the shock but express their fear through flight and escape behaviors instead of freezing.