Disruptions in primary visual cortex physiology and function in a mouse model of Timothy Syndrome

Professor Frank Sengpiel, Dr Rosie Offer (nee Craddock), Dr Cezar Tigaret

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About 85% of children with Timothy Syndrome have autism spectrum disorder. Sensory abnormalities are a core feature of autism spectrum disorder. Sensory abnormalities where individuals have either heightened or lessened sensitivity to specific smells, tastes, touch, pain, light or sound have previously been suggested to be caused by physical brain changes.

Our team wanted to look at how Timothy Syndrome might impact sensory processing in the mouse brain, and if this was associated with any physical brain changes. We decided to specifically study how the Timothy Syndrome type II (TS2) genetic variant (G406R) alters visual processing in the primary visual cortex of the mouse brain. The primary visual cortex is involved in processing basic information from everything we see around us. Without the proper functioning of the primary visual cortex, we would not have a mental picture of what you see in front of you.

Our research found that brain cells in the primary visual cortex of mice with the TS2 variant responded to visual information differently as compared to mice without the variant. We found that brain cells in the primary visual cortex of mice with the TS2 variant were more likely to respond when the mouse was looking at narrower black-and-white strips, and they were less likely to respond when the mouse was looking at wider black-and-white strips as compared to brain cells from the visual cortex of mice without the variant. This suggests that the TS2 variant causes changes in visual processing at a very basic level.

After finding this difference, we wanted to see how the TS2 variant might change the properties of brain cells and brain tissue in the primary visual cortex cells. We hoped that this might indicate how the TS2 variant causes the change in basic visual processing that we had found in the mouse brain. We found that brain cells from the visual cortex of mice with the TS2 variant had different electrical properties as compared to those from mice without the variant.

We found that the action potential – the electrical pulse that brain cells fire when they send a signal to one-another – was prolonged in brain cells from the primary visual cortex of mice with the TS2 variant as compared to those from mice without the variant. We also found that mice with the TS2 variant had an altered makeup of primary visual cortex brain tissue. Mice with the TS2 variant had a lower number of a specific type of cell within the visual cortex as compared to mice without the variant. Specifically, mice with the TS2 variant had a lower number of parvalbumin-positive brain cells in the primary visual cortex as compared to mice without the variant.

Either of the change in the electrical property of the single-cell or the change in brain-tissue makeup we found in mice with the TS2 variant could potentially alter how visual information flows through the primary visual cortex, which could be related to the changes in visual processing we saw in the mouse. We suggest more research is done into how the TS2 variant impacts sensory processing in the brain.

See the full report: Disruptions in primary visual cortex physiology and function in a mouse model of Timothy syndrome