Does Dim Light During the Day Impair Memory? Podcast with Antonio Nunez

Blue light has gotten a bad rap of late. Exposure to blue light at night suppresses production of melatonin, which in turn can disrupt sleep and misalign circadian rhythms (as discussed in my podcast with Professor Jamie Zeitzer). Societal awareness of these perils is growing, and lots of people have embraced blue-blocking glasses and other blue-light reducing tools, like F.lux for computer screens, that reduce exposure to short-wavelength light after sundown.

But are some of us throwing the baby out with the bathwater?

It is worth bearing in mind that the problems that are associated with intense, blue light are primarily an issue of timing, and it doesn’t deserve to be totally maligned. In fact, we recently posted a podcast episode with Professor Peter Light discussing how intense full spectrum light can penetrate the skin and thereby affect fat metabolism.

More recently, a fascinating study of rodents found that exposure to ultraviolet light improved performance in tests of motor learning and memory. So, blue light exposure isn’t bad, it just needs to be timed correctly.

The effects of light on cognitive performance have been well-documented, but underlying neural mechanisms are not as well understood. In particular, we don’t know a great deal about long-term effects of different patterns of ambient lighting, which is particularly relevant since most of us spend large portions of our days indoors in relatively dim lighting conditions. If blue light during the day is good for brain function, could this mean there are possible deleterious effects of insufficient light exposure?

That brings me to our latest podcast.

On this episode of humanOS Radio, I talk to Professor Antonio Nunez. Professor Nunez is principal investigator at the Nunez Lab at Michigan State University, where he studies neural and endocrine control of circadian rhythms in mammals. The lab aims to understand the neural pathways through which light influences function of the hippocampus – a brain region critical for learning and memory. To this end, they have been using Nile grass rats as a model organism to test the impacts of different ambient light conditions on learning and memory because these animals diurnal – they are awake during daylight hours like us humans.

In a previous study, researchers found that Nile grass rats that were housed under bright light (~1000 lux) during the day had more dopaminergic neurons after four weeks compared to rodents who lived in relatively dim light (~50 lux) during the day. Interesting. This suggests that ambient lighting might be making measurable changes in the brain, beyond just temporary shifts in arousal.

Accordingly, Nunez and his team designed this study to test how different intensities of ambient light affect cognitive performance and to elucidate underlying neural mechanisms. Let’s look at what they did.

The researchers took a group of Nile grass rats that had been exposed to a normal 12:12 hour light-dark cycle (~300 lux during the day) in a colony together. They separated them into individual cages and exposed each rat to either:

Then, to assess memory and spatial learning, the rodents were trained to navigate the Morris Water Maze task. Rather than even try to describe this, I’ll point you to this video so you can see how it works. This is a validated test of memory and hippocampal capacity – in fact, animals whose hippocampi have been removed cannot successfully complete this task. Afterward, rodents were sacrificed, and their central nervous systems were examined.

So, what happened?

The group that was exposed to dim light for four weeks struggled to learn the maze task. In fact, their performance did not differ statistically from random chance. In contrast, the rodents in the bright light group oriented their search to the correct region of the water pool, showing they remembered from their training where to look. They also took less time to locate the hidden platform.

Before you feel bad for the poor, lost rats in the chronic dim light group, here’s some good news: To determine whether these impairments were reversible, some of the rats were exposed to dim light for four weeks, but then were switched to bright light for another four weeks. These animals had full recoveries of task performance, suggesting that bright light can restore the losses associated with dim light.

When the brains of the rats were examined, the source of the performance deficits became clear.

Rodents exposed to dim light during the day lost about 30% of their hippocampal capacity. Specifically, there was a big drop in brain-derived neurotrophic factor (BDNF), a protein that is essential for learning and long-term memory. (For more on how BDNF works, check out this article.) Their hippocampi also had few dendritic spines – the connections that neurons use to communicate with one another. Finally, rats that had been switched from dim light to bright light had more BDNF expression and greater dendritic spine density, again suggesting that the deficits are related to dim daytime light, and that function can be restored with bright daytime light.

This study is the first to show that insufficient environmental light can lead to structural changes in the brain and worse cognitive performance. Importantly, the light levels studies were in an ecologically relevant range that might habitually be experienced by humans.

For the great majority of us who aren’t spending our days hunting and gathering, this could have important implications for our health and perhaps our productivity. The Environmental Protection Agency has reported that Americans spend, on average, about 90% of their time indoors.

Is it possible that spending too much time in dimly lit rooms and offices is affecting our ability to learn?

What can we do about our lighting environment to maximize cognitive performance and mental health?

Tune in below for more!

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And since we are on the subject of light, be sure to check out our courses by Greg Potter, PhD, on how the circadian system works and its critical effects on the body.

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Antonio Nunez - 00:07: Even if these changes in the brain occur due to lack of light exposure, that returning to a bright light environment can reverse those detrimental effects.

Kendall Kendrick - 00:24: Human OS, learn, master, achieve.

Dan Pardi - 00:33: Welcome everybody to this episode of Human OS Radio. Today, I am pleased to welcome Antonio Nunez, who is the principal investigator at the Nunez Lab at Michigan State University. He also serves as the associate dean of Academic Affairs and Postdoctoral Training in the graduate school. Dr Nunez, welcome to Human OS.

Antonio Nunez - 00:50: Thank you for having me.

Dan Pardi - 00:51: [We shared 00:00:51] in common, both having gone to Florida State, so go 'Noles.

Antonio Nunez - 00:55: That's right.

Dan Pardi - 00:56: You've come out with this very interesting research study about how light affects the brain. We're going to talk about that today, but before we get into that, tell us a little bit about your background and how you became interested in light overall and its effects on the body.

Antonio Nunez - 01:10: Well, I got my PhD from Florida State University working with [Fred Stephan 00:01:14], who was one of the discoverers of the location of the primary biological clock in the brain, and my dissertation with Fred related to how rhythms are synchronized to the light-dark cycle and how information about circadian signals are distributed throughout the brain. Ever since graduate school, I've been interested in circadian rhythmicity and the effects of light on the circadian system.

01:43: When I started my own lab here at Michigan State, I was working with traditional laboratory species, mice, rats, hamsters, and all of them are nocturnal. They are night active and therefore, different from us, from humans. It was not until my colleague, Laura Smale imported from Africa rodent that is related to mice and rats, but happens to be diurnal and that has been the focus of a lot of my work for the last 15, 20 years or so.

Dan Pardi - 02:15: You must be excited to see the explosion in interest in circadian rhythms overall. You are definitely early to the game.

Antonio Nunez - 02:22: Right, and it was very rewarding to see the Nobel prize going to [really 00:02:27] the pioneers in the field.

Dan Pardi - 02:28: Tell us more about what your lab has looked at over, let's say, just the last couple of years since you've been working this for 15 years.

Antonio Nunez - 02:34: This work started with collaboration with Laura Smale and Lily Yan who are both colleagues of mine here at Michigan State and we focus a lot on differential effects of light on behavior in diurnal and nocturnal species. What we found was that there's a remarkable, almost opposite effect of light on behavior where if you turn on the lights, a diurnal species, regardless of time of day, will wake up and be active. Same light presented to a nocturnal species like rats or mice will induce [with short latency 00:03:12] sleep. So that told us that if we want to understand how light affects humans, we had to focus on a diurnal mammal to answer questions about mechanism. So that's the background for this particular paper.

Dan Pardi - 03:28: What are some of the neuroanatomical players that are involved in coordinating some of these signals?

Antonio Nunez - 03:33: The original [key 00:03:34] projection, which was discovered in the 1970s, is a direct projection to the hypothalamus, to the superchiasmatic nucleus where the principal circadian oscillator in mammals resides, but now we know that projections from retinal ganglion cells that are not involved in visual perception per se, but they're involved in transduction of light information project to a number of regions in the brain that are not involved with vision. They're not involved with image formation, but they are responsible for more reflexive effects of light as well as for synchronizing biological clocks to the light-dark cycle. You can have an individual that is blind with respect to being able to form images, but if this ganglion cells, these cells in the retina that photoreceptive themselves have a substance called melanopsin, they can respond to light even though they don't see, consciously see light.

04:35: I'm looking at parts of the brain that are retinorecipient, receive input from the retina, but are not involved in seeing. They're not involved in visual perception. Some of these effects of light on arousal, on activity, on sleep are mediated by those projections from the retina as well as the synchrony of circadian rhythms to the light-dark cycle.

Dan Pardi - 04:57: You said something earlier that I'm going to repeat because it was so interesting. In diurnal rodents, like this type that you used from Africa, when they are exposed to light, it will wake them up no matter what time of day it is.

Antonio Nunez - 05:07: Exactly.

Dan Pardi - 05:08: Conversely, if you're a nocturnal species, and you're exposed to light, that signal makes them go to sleep and rather quickly, so light itself is not necessarily doing one thing, but it is having a strong response depending on whatever the nature of your awake timing is.

Antonio Nunez - 05:22: Correct.

Dan Pardi - 05:23: We've got a clear signal here. In your paper, you talk about how the effects of light on cognitive performance are well known in humans. Tell us a little bit more about the findings that led up to you generating a hypothesis and the protocol for the study.

Antonio Nunez - 05:39: As you said, there is convincing evidence in the literature with humans, different populations showing that different cognitive competencies are improved by exposing humans to bright light, and since most of the work with the effects of light in laboratories looking for mechanisms has been done with nocturnal species, there was this gap in our knowledge about mechanism, how is light affecting cognition in a diurnal species? That's why we took advantage of this diurnal rodent to ask questions about mechanism. The first thing we had to do was to show that in our animal model, in our diurnal rodent, the grass rat or Arvicanthis, there was an actual effect of light intensity on cognitive functions.

06:26: Our first task was exploratory, which was the work of one of our graduate students, Joel Soler, and what we asked Joel to do was to test animals that had been either dim light or bright light for four weeks on a task that depends upon an intact and functioning hippocampus, which is part of the brain that is essential for normal human memory. It's also very important for navigation and spatial memory, recognizing the places you have visit, remembering where you park your car, if you park your car, jump on an airplane for a week and come back to the airport, things like that.

07:03: What he found was a remarkable effect of light illumination on the performance, the retention of this task that involves using a very common apparatus called Morris water maze where the animal needs to navigate and to find safe platform in an otherwise deep water environment.

07:22: What Joel found was that these animals that have been in dim light basically overnight, over a 24-hour period between days of training would forget what they learned the day before and show very poor performance as a function of time since learning the task. The animals that were in bright light show full retention, what you would expect from animals that are using their hippocampus to an optimal level. That was the first step was to establish in our animal model an effect of light on cognitive performance. The hypotheses that we had was that it was probably a change in the hippocampus since that task depends upon the integrity of that part of the brain.

08:04: We focus on the hippocampus and we found two remarkable effects of four weeks in dim light. One was a chemical change. Hippocampus of the animals in dim light had significantly less of a substance called BDNF is a growth factor that is essential for plasticity and retention of acquired information in the hippocampus. There was a measurable chemical change in the hippocampus in four weeks. It was not an immediate change after a week in dim light, but there was no change so it had to be a more sustained exposure. But after four weeks, both the memory was deficient. They're cognitive performance was challenged and there was a reduction in this growth factor.

08:49: We took it one step further and look at the morphology of the neurons in the hippocampus. We have known for many years that the inputs to the hippocampus in the particular area that we looked at depend upon the presence of what are called dendritic spines, which are just extensions of the neurons that receive the information from other neurons. They are the post-synaptic receiving end of these neurons. We found a remarkable reduction in the number of dendritic spines in the hippocampus after four weeks in dim light. The reduction was statistically significant, but the effect was close to 30% reduction so it was a big effect that correlated with the reduction in growth factor production and correlated with the behavioral deficits.

09:40: Our contribution here was to at least suggest a mechanism that is responsible for how bright light or dim light can differentially affect cognitive functions in diurnal species and by extension in humans as well.

Dan Pardi - 09:55: You exposed these diurnal rats to dim light for a period of four weeks and then, you measured the amount of BDNF or this growth factor that was present in the brain that correlated with a 30% reduction in the amount of hippocampal neurons and that loss of hippocampal neurons, which are associated with memory formation also paired with a reduced performance on this memory task, this water maze task.

Antonio Nunez - 10:17: Correct, but we didn't find a reduction in the number of neurons. We actually didn't count neurons. We count how many dendritic spines were present and that's the 30% reduction.

Dan Pardi - 10:28: Thank you for that clarification. That's useful. This is a bit scary because we are diurnal animals as well. We spend 90% of our time indoors, much different than how we used to live as humans prior to the modern age. Are there some hopeful signs here from your research, too?

Antonio Nunez - 10:44: The good news is that we took animals that had been in dim light for four weeks and we transferred them to bright light for another four weeks so they were moved back to bright light after being exposed to four weeks of restricted light. What we found was that everything returned to normal. The performance, the memory ability of the animals returned to normal. The production of BDNF returned to normal and the number of dendritic spines that had been reduced in dim light returned to normal. The good news is that even if these changes in the brain occur due to lack of light exposure, returning to a bright light environment can reverse those detrimental effects. The caveat here is that we use young adults. These were relatively young animals. One question that is there for future research is whether or not this ability to rebound persists in aging organisms.

Dan Pardi - 11:42: Were you able to measure how quickly the neurons that had been exposed to the dim light condition were rescued by bright light exposure, or you're just able to look at before and after?

Antonio Nunez - 11:53: No, that's also for future research, to see how quickly and whether or not there might be trade offs like what if it's one week of very intense bright lights. All those future parametric studies that should clarify the time course both on the decay and the rebound.

12:08: We know with respect to the decay that one week of exposure to dim lights doesn't do anything so we know that much, but we don't know if two would be enough or three. We know that four can do it. One doesn't. We know that four weeks of bright light after four weeks of dim light can reverse the effects, but we don't know if it happens sooner or it could be accelerated by increasing the light intensity or whether or not it interacts with the age of the organism. So all those are really good questions for future studies.

Dan Pardi - 12:41: Have you exposed the diurnal animals to mostly dim light, but they did receive an hour of bright light per day in that [in-light 00:12:49] four-week period? Is there some sort of Pareto principle where you get 80% of the effect of preservation of these healthy dendritic spines and if you just get enough per day?

Antonio Nunez - 12:58: Right. We don't know that, another interesting manipulation so give them like a pulse of one hour of light at the end of the day or at the beginning of the day and see if that's enough to sustain normal functioning. Those are all good questions, but would take a lot of work to answer them.

Dan Pardi - 13:14: My mentor, Jamie Zeitzer at Stanford, he's doing the light pulses to shift circadian timing, but what I'm immediately thinking about now is the potential utility of wearing a device like that in an office. You put it on for 10 minutes a couple times a day just to get bright light exposure through the flashes. Could that actually help to preserve cognitive function and neural health?

Antonio Nunez - 13:33: Or you can spend four weeks in Tallahassee or something.

Dan Pardi - 13:36: Antonio, are you suggesting that employers should give their employees one week off to go to the beach every four weeks? It sounds like-

Antonio Nunez - 13:42: Absolutely, especially during winter in Michigan for sure.

Dan Pardi - 13:44: You are now my most popular podcast guest ever. The next interesting question that you're going to look into is if orexin given to these rats during the dim light exposure has the ability to rescue and recover the neurons like the light exposure does?

Antonio Nunez - 13:59: That suggestion, that hypothesis comes from my collaborator, Lily Yan. She has looked at orexin abundance in diurnal animals, exactly the same species that have been kept in dim light or bright light, and she sees [a reliable 00:14:13] reduction in orexin in animals that are in dim light. There are two other things that are pertinent here. One, we talked at the beginning about how the key retinal projections that go to different parts of the brain involved in responses to light are not associated with visual perception. We have a number of [inaudible 00:14:33] and the hippocampus is not one of them. We're seeing an effect of light on hippocampal structure and function, but we know in our species as well as in traditional nocturnal rodents that the retina doesn't project directly to the hippocampus, but there's retinal input to the orexin-producing neurons. Orexin neurons project to a multitude of places, but one of them is the hippocampus.

15:00: Lily Yan's hypotheses based on her observations [of that reduced 00:15:03] orexin abundance in dim light is that orexin input to the hippocampus is a mediator of this [effect applied 00:15:12]. You had dim light, reduced orexin input on the hippocampus and, therefore, a change in BDNF production and dendritic spines.

15:22: The next step in her side of this research project is to take animals that are in dim light and through different approaches, increase orexin production and see if that reverses the effects of dim light and in parallel, look and see if blocking the effects of orexin in the hippocampus can diminish BDNF and dendritic spines and impair behavior in animals that are in bright lights. That's Lily Yan's next experiment going on in her lab at this point.

Dan Pardi - 15:53: That'll really help to flesh out the mechanism and for the listener, just to add a little bit more context, orexin is a neuro peptide that is produced in perifornical regions of the hypothalamus. These are the neurons that go missing when somebody develops the condition of narcolepsy. What's so interesting here is that if we're not getting enough light during the day, we're getting input to these orexin-producing neurons when we get adequate light and then, that will facilitate BDNF growth factor in the hippocampus to keep our memory forming neurons and dendritic spines healthy and functioning. This next work is going to look at this in multiple ways, pharmacological manipulation of orexin and also blocking orexin's effects to just challenge it from two different sides. That would help 'cause one potential therapy instead of having people get outside because that can be difficult if you have a job at a desk like most people do, would be a pharmacologically delivered orexin-A intranasally or orally. Yeah, that could be a potential way to keep our brains healthy.

Antonio Nunez - 16:46: Yeah, the intra-nasal avenue is really interesting. In Joel Soler, the graduate student who's working in this project, is doing a pilot just to see if that approach would work with our animals [to see if just 00:16:58] peripheral administration through the nasal cavities could work in reversing the effects of dim light.

Dan Pardi - 17:05: Once again, I'm a big fan of the ancestral paradigm for health, so what were our lives like prior to modernity and all the invention, including buildings and air conditioning and jobs, all these forces that actually get us to live in a way that is very normal now, but actually pretty unique and weird to our physiology? There's another great example is just the amount of light that we receive during the day and yet again, another important aspect of it, keeping our hippocampal memory forming neurons strong as this work indicates by Dr. Nunez. Dr. Nunez, thank you so much for coming onto the show and I really appreciate your time and this contribution. It's fascinating stuff.

Antonio Nunez - 17:41: My pleasure. Thank you.

Kendall Kendrick - 17:44: Thanks for listening and come visit us soon at humanos.me.