A “switch” for the winter blues

We’ve all been there. Mid-winter morning, you crawl out of bed, slouch towards work, and pass the day in a hazy daze. There seems to be no concept of time, just never-ending darkness and cold. You’re not depressed, just…bleh.

Well, rats have that feeling too. Being nocturnal though, they prefer long nights to long days – too much sun, and you’ll get one anxious and depressed rodent. Taking advantage of our shared woes, in this paper, researchers exposed rats to two different light regimes, and peeked into their brain for clues on their “summer” blues.

Davide Dulcid et al. Neurotransmitter Switching in the Adult Brain Regulates Behavior. Science 340, 449 (2013).

One cohort of rats received 19 hours of dark and 5 hours of light (long-dark), while the other unlucky bunch got the opposite regime (long-day). A week later, researchers zoomed in on a brain area called the hypothalamic nuclei, which receives information from the eyes. To the researchers’ surprise, compared to long-day rats, long-night rats had dramatically more dopamine-releasing neurons and less somatostatin-releasing neurons. Dopamine, a “star” neurotransmitter, is involved in motivation, mood and cognition. Somatostatin, the lesser-known counterpart, is a peptide neurotransmitter that seems to be involved in the regulation of stress responses. Intriguingly, this increase in dopamine neurons in long-night rats was reversible: if they went through another week of long-day regime, the dopamine neuron numbers went back down to normal.

So what’s going on? Perhaps long-nights signaled the hypothalamic nuclei to produce more dopamine-releasing cells and kill off somatostatin-releasing ones? Additional experiments ruled this out. Looking closer, researchers found that the different light-dark cycles indeed changed the ability of individual neurons to synthesize either dopamine or somatostatin. In other words, single neurons are switching their predominant neurotransmitter in response to different lengths of light and dark.

…Wait, what?! Neurons can release more than one type of transmitter?!

Yes, that’s right. For a long time neuroscientists believed that individual neurons can only make and release a single type of neurotransmitter. That’s why we traditionally call them “dopamine neurons” or “serotonin neurons”. But most, if not all, neurons are not married to their particular neurotransmitter - they can switch between or co-release multiple messengers, making traditional names mute (and why the neurons in this study were called dopamine-releasing neurons, since they can also release somatostatin if need be). These switches are often accompanied by corresponding changes in the receptor to ensure functional outcomes. Since neurotransmitters are a major way neurons communicate with each other, changing the “message” is a powerful way to change how neural circuits operate, and maybe, how animals behave.

Which is indeed the case here. Researchers tested the rats on two assays (elevated plus maze and forced swim test, for those wanting the nitty-gritty), which measure mood, anxiety and depression. Strikingly, compared to control rats (12 hours day/night), long-night rats were less anxious (spent more time in the open/scary part of the maze) and less depressed (spent more time struggling in the water before they gave up). Long-day exposure produced the opposite effect. This tells us that longer nights made happy, relaxed rats, while longer days brought on the blues.

Finally, researchers tied the story together, and showed that the changes in mood are in fact mediated by neurotransmitter switching. Long-day rats had decreased dopamine to somatostatin signaling, which correlated with increased amounts of circulating stress-related hormones. The opposite was true for long-night rats.

TL;DR: Increased dark -> somatostatin to dopamine switch -> less depressed mood; increased light -> dopamine to somatostatin switch -> increased stress hormones -> more depressed mood

This is a squeal-inducing study no matter from which angle you look at it. From a plasticity perspective, it shows that the adult brain is very adaptable, to the extent that LIGHT can influence which neurotransmitter is released. From a neurobiology perspective, it helps us start to decode how a mixture of neurotransmitters operates on neural networks. From a systems point of view, it offers a link between mood, light-dark cycle and neurotransmitter switch. From a therapeutic perspective, it illustrates why light therapy is helpful in seasonal affective disorders (SAD).

So next time you’re feeling the winter blues, turn on a light box and shine some light. And thank your neurons for “switch”ing off the blues.

Dulcis D, Jamshidi P, Leutgeb S, & Spitzer NC (2013). Neurotransmitter switching in the adult brain regulates behavior. Science (New York, N.Y.), 340 (6131), 449-53 PMID: 23620046