Food for Thought

08 February 2016

Interview with

Dawn Loh, UCLA

The midnight feast will be a concept familiar to many youngsters but, increasingly, older kids - including some in their 30s, 40s and 50s - are embracing lifestyles that lead to sleep deprivation and eating at what could be regarded as "all the wrong times" including late into the night. Often this is to meet deadlines or cram in work around family life and other obligations. But it could be having a detrimental effect on your memory, by throwing the body clock off kilter in your hippocampus, the part of the brain where memories are first made. Chris Smith spoke to Dawn Loh...

Dawn - We took two groups of mice. We put one of them under fairly normal housing conditions and allowed them to eat when they should be active. In the second group of mice, we gave them food during what should’ve been their sleep time and then we tested their ability to learn and remember after being housed in these two conditions.

Chris - Now, these mice that you are feeding, the mouse equivalent to the midnight feast to, were they being woken up for that? In other words, were you depriving them of sleep and upsetting them in other ways?

Dawn - In this study, we used some automated feeders so we didn’t have to disturb the mice. So we didn’t have to go into the cage and wake them up and give them food. But it is true that the mice had to stay up during a time that they would not normally want to stay up to eat their food. And they actually adapted to that within about 6 days. What happened to their sleep was that although the sleep in the first few days was disturbed, the sleep caught up later on so that they no longer was sleep deprived when you considered them over a 24-hour cycle.

Chris - What sorts of measurements were you making on the mice when you did this to them?

Dawn - Well, we were able to test them at two different times of day with the same test. So with one group of mice, we tested them at what should have been their normal week time when they should perform very well on the test that we called ‘novel object recognition test’. So this is a test where we give them two identical objects and we train them to recognise them. The next day, we replace one of those objects and a normal mouse would spend more time with the new object, the novel object. That’s how we would know that the mouse remembers the old object. What happened to our two groups of mice was that while the aligned mice, the mice who were eating during their normal time performed this test remarkably well, spending most of their time with the new object, the novel object. The misaligned mice who were eating during their sleep time spend significantly less time with the new object and in fact, they didn’t pass the criteria for this novel object recognition test at all.

Chris - This would suggest that something is impaired in their ability to form memories.

Dawn - That’s right. We suspect some of these problems may be arising in the hippocampus and this suspicion is borne by previous evidence from another lab showing that the clock in the hippocampus may actually shift according to when you eat. So we specifically looked at a hippocampal dependent learning and memory test where we train a mouse to recognise a specific context with a fearful stimulus. Again in this case, the misaligned mice were unable to remember the context. So they had a hippocampal-specific loss of memory.

Chris - How do you account for this? What do you think is going on? Is this just sleep deprivation? It would argue not if they're making up the sleep. So, what underlies this?

Dawn - We think that perhaps the clock in the hippocampus is changing the state of the hippocampus. The clock that I'm referring to is this endogenous set of genes that we have that causes a feedback loop that autocompletes within the day. This little clock is in each and every one of our cells. We know that the cells in the hippocampus express this clock and it’s a rhythmic clock, and it drives certain types of physiology in the hippocampus. What we think is going on in these misaligned mice is that the master clock which is driven by light, it’s in a different part of the brain called the suprachiasmatic nucleus. It’s ticking along and following the light/dark cycle. There are certain other clocks in the rest of the body that might be more prone to being entrained or being driven by food so some of these clocks in the body include the liver and quite surprisingly, the hippocampus, so some of these other clocks are starting up at a different time compared to the master pace maker in the brain. What we think we’ve done in these misaligned mice is set up this internal desynchronization between some metabolic parameters and other brain function.

Chris - So in other words, the hippocampus is effectively optimised to operate at the wrong time of day in these mice.

Dawn - That’s right. That’s what we think is happening.

Chris - If you were then to test the mice at the time when the hippocampus was more optimally operating, would they perform better?

Dawn - So we did those tests but when we performed those tests at the opposite time of day, we found that the mice were still not performing well on the test.

Chris - So, how do you explain that then?

Dawn - We don’t have a very good explanation for that at present. We think that perhaps the internal desynchronization has led to some changes in the hippocampus that are long lasting.

Chris - If you move your misaligned mice so that you start to feed them at the right time again, do they go back to normal?

Dawn - That is an experiment that we have yet to do and would definitely be part of our next study. Whether this is a long term chronic effect or whether the mice can recover.

 

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