The Difference Between Night and Day in Cognition by Sonny

The Difference Between Night and Day in Cognition

With few exceptions, every cell in the body has its own internal clock, responds to the Earth’s 24-hour day-night cycling—circadian rhythms. Cells whose activity determines an organ’s function are often timed differently, but they all respond like clockwork to the arrival and departure of sunlight as directed by the brain. It’s an amazing chemical feat of coordination, first discovered in cyanobacteria, tiny “quasi-animals” that rely on plant-like photosynthesis. The chemical and genetic details are quite well known for such a complicated system, but they boil down to atomic movements synchronized with Earth’s rotation around the sun (see Dierickx, 2018 for a review). Those details are beyond the scope of this commentary, but, suffice it to say, these circadian rhythms also affect behavior. For instance, humans are diurnal and don’t normally eat at night because secretion of glucose from the liver and it’s “offsetting” hormone, pancreatic insulin, are coordinated with solar cycles, which balance (or imbalance) is transmitted to brain regions directing the drive for food. The brain’s central pacemaker, the “master conductor” the directs this cycling, is the suprachiasmatic nucleus (SCN), a cluster of neurons with direct connections to the retina’s light sensitive cells. The SCN’s output goes to virtually every part of the brain and body.

Importantly, gene expression, the first step in producing proteins that guide every cell’s function, also experiences circadian rhythms (see Kim, 2018, to learn how this is done). As a result, medical science pays attention to circadian rhythms for drug effectiveness; take them in the morning or at night. Most of the drugs known to be so affected by circadian rhythms are directly related to metabolism (e.g., statins and heart medications of various sorts), thus, it’s still unclear if the efficacy of “behavior-managing drugs” like selective serotonin inhibitors (SSRIs) are similarly affected by circadian rhythms (De Giorgi, 2013). I suspect they are because “82.2% of genes coding for proteins that have been identified as druggable targets by the U.S. Food and Drug Administration show cyclic changes in transcription in at least one tissue” (Mure, 2018). Additionally, drugs affecting melatonin production are sensitive to circadian rhythms (Simko, 2009), melatonin is produced by gut bacteria (Anderson & Maes, 2015), and melatonin is a major factor impacting the gut-brain-axis (what you eat impacts your behavior). Thus, the evidence points in favor of my suspicions that drugs affecting behavior should, like statins and heart drugs, be timed to circadian rhythms.

The chemical and genetic foundations of circadian rhythms come from studies in cyanobacteria, and they’re the same throughout the animal kingdom, but most knowledge of the SCN comes from experiments on mice. Mice are nocturnal animals, so we’ve assumed that the body’s pacemaker activities in diurnal animals like humans are simply shifted by 12 hours. We are probably wrong, or so conclude Mure and colleagues, who performed their experiments on diurnal baboons. Not only did their research suggest that this “12-hour shift” assumption regarding gene expression is incorrect, but it was different than the mouse on a body region-by-region basis. What struck me as especially important to the evolution of human cognition was what they observed about circadian gene expression in the cerebellum, one of those regions differing between nocturnal mice and diurnal baboons.

I conceptualize the cerebellum as a region specialized in “simple” computations utilized by all other brain regions, thus acting analogous to a “parallel computer” in expanding the computational power of functionally specialized brain regions. The cerebellum’s computational power is probably accounted for by the sheer number of its small, uncomplicated granular neurons, comprising about 75% of the brain’s total neurons. Even small neurons are voracious energy consumers, so this probably means the cerebellum is more sensitive to solar cycles than other brain regions. Not surprisingly, Mure and colleagues observed a “quiescent period” in genes transcribed (active) in the cerebellum. The set of genes active in a cell is its “transcriptome,” and the same type of neuron in different brain regions has a different transcriptome, bespeaking the region’s specialized function. That is, Mure and colleagues observed that in the first half of the night, cerebellar gene expression is “slowed down,” suggesting it is less capable of performing its most powerful calculations during this time. Metaphorically, the cerebellum is announcing, “Sorry, other brain regions, I’m off line now.” This reconciles with the belief that memory consolidation occurs during sleep, which consolidation presumably requires less energy. Thus, I suspect the brain’s computational power, and, subsequently, its cognitive capacity, is suboptimal during the first half of nighttime, important information for late hour work and ancient humans.

References

Mure, L. S., Le, H. D., Benegiamo, G., Chang, M. W., Rios, L., Jillani, N., … & Panda, S. (2018). Diurnal transcriptome atlas of a primate across major neural and peripheral tissues. Science, eaao0318. http://science.sciencemag.org/content/359/6381/eaao0318

De Giorgi, A., Menegatti, A. M., Fabbian, F., Portaluppi, F., & Manfredini, R. (2013). Circadian rhythms and medical diseases: does it matter when drugs are taken?. European journal of internal medicine, 24(8), 698-706. www.ejinme.com/article/S0953-6205(13)00103-9/abstract

Simko, F., & Pechanova, O. (2009). Potential roles of melatonin and chronotherapy among the new trends in hypertension treatment. Journal of pineal research, 47(2), 127-133. https://insights.ovid.com/pineal-research/jpinr/2009/09/000/potential-roles-melatonin-chronotherapy-among-new/2/00005208

Anderson, G., & Maes, M. (2015). The gut–brain axis: The role of melatonin in linking psychiatric, inflammatory and neurodegenerative conditions. Advances In Integrative Medicine, 2(1), 31-37. http://www.aimedjournal.com/article/S2212-9626(14)00081-9/abstract

Kim, Y. H., Marhon, S. A., Zhang, Y., Steger, D. J., Won, K. J., & Lazar, M. A. (2018). Rev-erbα dynamically modulates chromatin looping to control circadian gene transcription. Science, eaao6891. http://science.sciencemag.org/content/early/2018/02/07/science.aao6891

Dierickx, P., Van Laake, L. W., & Geijsen, N. (2018). Circadian clocks: from stem cells to tissue homeostasis and regeneration. EMBO reports, 19(1), 18-28. http://embor.embopress.org/content/19/1/18

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