Serotonin neuron abnormalities in the BTBR mouse model of autism.
BTBR mice have a local serotonin shortfall in the hippocampus, giving us a spot to aim new treatments.
01Research in Context
What this study did
Guo et al. (2017) looked inside the brains of BTBR mice. These mice act like people with autism. The team counted serotonin cells and fibers in two places: the hippocampus and the raphe. They used dyes and a microscope. No drugs or training were given.
What they found
The hippocampus had fewer serotonin fibers and less serotonin itself. The raphe tried to fix this by making more cells, but the fix did not reach the hippocampus. The result is a local shortage of serotonin in a key memory-and-social area.
How this fits with other research
Ryan et al. (2019) showed BTBR males avoid stranger mice but still like social smell. The low serotonin shown here may explain why they stop at the smell and do not move closer.
Reynolds et al. (2013) found that adding toys and tunnels cut grooming time in half, yet the grooming stayed rigid. The new study hints why: serotonin is low only in the hippocampus, not in motor circuits, so the ritual stays fixed even when time drops.
Whitehouse et al. (2014) saw the same serotonin 2A receptor gene linked to autism in families. The mouse data now give a brain picture for that genetic link.
Why it matters
You now have a clear brain target. When BTBR mice show social rigidity, the problem is not a global serotonin lack; it is a wiring gap in the hippocampus. Future drugs or DREADDs can aim there. For now, pair social tasks with odor cues, because the nose-to-hippocampus route still works even when full contact fails.
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02At a glance
03Original abstract
The inbred mouse strain BTBR T+ Itpr3tf /J (BTBR) is studied as a model of idiopathic autism because they are less social and more resistant to change than other strains. Forebrain serotonin receptors and the response to serotonin drugs are altered in BTBR mice, yet it remains unknown if serotonin neurons themselves are abnormal. In this study, we found that serotonin tissue content and the density of serotonin axons is reduced in the hippocampus of BTBR mice in comparison to C57BL/6J (C57) mice. This was accompanied by possible compensatory changes in serotonin neurons that were most pronounced in regions known to provide innervation to the hippocampus: the caudal dorsal raphe (B6) and the median raphe. These changes included increased numbers of serotonin neurons and hyperactivation of Fos expression. Metrics of serotonin neurons in the rostral 2/3 of the dorsal raphe and serotonin content of the prefrontal cortex were less impacted. Thus, serotonin neurons exhibit region-dependent abnormalities in the BTBR mouse that may contribute to their altered behavioral profile. Autism Res 2017, 10: 66-77. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Autism research : official journal of the International Society for Autism Research, 2017 · doi:10.1016/j.ijdevneu.2007.09.008