Yes, we were looking to see whether a high fat diet led to stalls in non-AD mice and if the high fat diet led to a synergistic increase in stalls in AD mice — by this we mean the number of stalls in high fat diet AD mice is larger than the sum of the impact of AD and high fat diet alone.
We have not yet examined the impact of sleep duration or quality on the rates of capillary stalls. Monitoring and disrupting sleep in mice is tricky to do well and we would need an appropriate collaborator, I think. We did take an initial look to see if there were differences in the number of capillary stalls after a period of wakefulness as compared to after a period of sleep. We did not see a strong effect, although there was a trend toward more stalls after a period of wakefulness. We have not yet followed up on this, mostly due to other priorities.
We measure cognitive performance using a battery of relatively standard tests. The ones we use include: the novel object recognition test, the object replacement test, the Y-maze test, and a few others. These tests tend to take advantage of the natural curiosity and exploratory behavior of mice. For example, in the novel object recognition test, the mice are placed in a box with two objects (which they tend to spend much of their time exploring). After a few minutes, we take them out of the box for about an hour. We then put them back in the box, but exchange one of the objects for a new object. Mice tend to spend more time exploring the new object, if they have formed a memory of the first objects and recognize the new one as being new. So, mice with impaired cognitive function spend about the same amount of time exploring the old and the new object, while mice with intact memory function spend significantly more time exploring the new object.
We have not tested the impact of a cognitively stimulating environment for the impact on capillary stalls. We do house all our mice in groups and with toys (this is pretty standard housing conditions), but I’m not sure this is truly “cognitively stimulating.” So, right now, we do have minimum cognitive enrichment and the stalls are still there. I’m not sure how to make the mouse housing conditions robustly more cognitively engaging for the animals. This has been done with rats, which were housed in large groups with a lot of dirt where they could build warrens, and led to remarkable cognitive and neurological differences. Mice are less social animals, so it is not clear such housing options would work well.
Thank you for these suggestions. They would each be interesting to pursue.