



A study published earlier this year in Science shows that changes in photoperiod cause a novel neural plasticity, neurotransmitter switching. Neurotransmitter switching was shown to directly cause changes in measured anxiety and depression.













The winter solstice is almost upon us, which means daytime is scarce. The lack of daylight during the winter can be more than an inconvenience for people suffering from Seasonal Affective Disorder (SAD). For residents of the northern latitudes, the lack of light during the winter is especially acute. A study that came out earlier this year in Science suggests that changes in photoperiod cause a physical phenomenon, called neurotransmitter switching (Neurotransmitter Switching in the Adult Brain Regulates Behavior, 2013. Dulcis, et al.). Perhaps, more interesting, is that this study highlights a new type of neuronal plasticity; one that is directly influenced by our environment.

The brain is incredibly complex. Neuroscientists estimate that the human adult brain contains 1011 neurons, each with 104 synaptic connections (connections between neurons). There are 100 different known classes of neurons and 100 different neurotransmitters, the small, secreted molecules that neurons use to communicate with each other. In addition to its structural diversity, the brain is incredibly dynamic. Synaptic connections are being created and destroyed with every new experience. In the hippocampus, new neurons are born. And now the aforementioned study demonstrates that our neurons can change their type in the adult brain, a phenomenon called neurotransmitter switching. Neurons are generally excitatory, releasing neurotransmitters such as glutamate and aspartate, or inhibitory, releasing neurotransmitters such as glycine and GABA. Neurons may release more than one neurotransmitter, but their neurotransmitter release concoction is fixed after the birth of the neuron-or so we thought.

In the aforementioned study, the researchers set mice in three different photoperiod conditions. The experimental photoperiod conditions were 19 hours light and 5 hours dark and 5 hours light and 19 hours dark. The control condition was split 12 hours light and 12 hours dark. It should be noted that mice are nocturnal, and thus more comfortable in the dark condition. If we were to extrapolate the results to humans, we would flip the light and dark conditions. The mice were maintained in these conditions for one week. At the end of the week the mice were subjected to behavioral tests to measure anxiety and depression. Sections in the lateral preoptic area (LPO), paraventricular nucleus (PaVN) and periventricular nucleus (PeVN) were analyzed for somatostatin and dopaminergic neuron switching.

Dopaminergic neurons were quantified using tyrosine hydroxylase, an enzyme necessary for dopamine production. The ratio of dopaminergic neurons to total nuclei increased in the dark condition relative to the light and dark 12:12 hour control. In contrast, the ratio of dopaminergic neurons to total nuclei decreased in the dark condition relative to the control. The data for the dopaminergic neuron quantification can be seen in the figure A below. In addition, an example of the confocal immunochemistry images the researchers used to quantify the dopaminergic neurons is displayed in figure B.

The authors quantified somatostatin neurons as well. A pattern in reverse of the dopaminergic neurons is observed. The somatostatin neurons decreased with an increasingly dark photoperiod. The data can be seen in the figure below.

The results discussed so far do not eliminate the possibility that the changes observed are a result of neurogenesis (forming new neurons) or apoptosis (cell death). The authors used BrdU, a neurogenesis marker, to demonstrate that neurogenesis was not taking place. An apoptosis assay called TUNEL was used to show that apoptosis was not occurring at a higher rate than under homeostatic conditions. Thus, the researchers showed that photoperiod was directly responsible for switching the neuronal neurotransmitter identity. The presynaptic neuron (the neuron releasing the neurotransmitter into the synapse) neurotransmitter identity directs the neurotransmitter receptor identity of the postsynaptic neuron (the neuron reacting to the neurotransmitter). Thus, we can think of this neurotransmitter switching as synaptic, rather than neuronal, in nature because both the presynaptic and postsynaptic neurons are changing their respective neurotransmitter release and receptor machinery.

The authors tested the mice for anxiety and depression following the experimental photoperiods. Anxiety was tested using a elevated plus maze and depression was evaluated with a swim test. According to the test results, the mice in the dark photoperiod had significantly less anxiety and depression. Recall that mice are nocturnal and, thus, are more comfortable in dark. This result parallels people being afflicted with SAD during the short days of the winter months.

To demonstrate that the behavioral changes were a direct result of the neurotransmitter switching the authors looked at behavioral changes after lesion of dopaminergic neurons. Anxiety and depression were induced after lesion of the dopaminergic neurons. However, treatment with a dark photoperiod restored the dopaminergic neuron balance and removed symptoms of anxiety and depression. Similarly, doctors have found that light therapy is effective in treating SAD.

This study is certainly important to neuroscience because it demonstrates a new type of neuronal plasticity. Furthermore, the study demonstrates something we all can appreciate: the incredible influence that our environment and lifestyle can have on us physically and mentally. On Exercise Medicine our mission is to help better understand the relationship between our lifestyle, often exercise, and our physical health and well-being. Light exposure seems mundane compared to other lifestyle choices that affect our health such as physical activity, mental stress, sleep and nutrition. This study demonstrates how fragile our bodies are to the environmental and physical stresses we are subjected to.

Stay healthy this winter, your body will thank you!

Update: I spoke with the principal investigator of the lab that discovered neurotransmitter switching. He told me they are now exploring the effect of running on neurotransmitter switching. So more to come when that research is published!