In the last decade advances in human neuroscience have identified the critical importance of time in creating long-term memories. Circadian neuroscience has established biological time functions via cellular clocks regulated by photosensitive retinal ganglion cells and the suprachiasmatic nuclei. Individuals have different circadian clocks depending on their chronotypes that vary with genetic, age, and sex. In contrast, social time is determined by time zones, daylight savings time, and education and employment hours. Social time and circadian time differences can lead to circadian desynchronization, sleep deprivation, health problems, and poor cognitive performance. Synchronizing social time to circadian biology leads to better health and learning, as demonstrated in adolescent education. In-day making memories of complex bodies of structured information in education is organized in social time and uses many different learning techniques. Research in the neuroscience of long-term memory (LTM) has demonstrated in-day time spaced learning patterns of three repetitions of information separated by two rest periods are effective in making memories in mammals and humans. This time pattern is based on the intracellular processes required in synaptic plasticity. Circadian desynchronization, sleep deprivation, and memory consolidation in sleep are less well-understood, though there has been considerable progress in neuroscience research in the last decade. The interplay of circadian, in-day and sleep neuroscience research are creating an understanding of making memories in the first 24-h that has already led to interventions that can improve health and learning.
Keywords: Circadian timing, long-term memory, social time, spaced learning
Circadian cycles create the patterns of wake and sleep in which short and long-term memories are created. Social factors leading to mistiming wake and disrupting sleep can have a negative impact on these memory functions. Memory processes in the initial 24-h cycle are critical in determining what is encoded into long-term memory (LTM) rather than left to fade in short term memory (STM). There are many stimuli that can trigger LTM but, in this review, we focus on spaced repetition leading to LTM of bodies of complex information, an essential process in learning.
The fundamental role of circadian timing processes has been emphasized by the award of the Nobel Prize in 2017 in physiology or medicine to Hall, Rosbash, and Young for their discoveries of the genetic mechanisms that create circadian 24-h timing in drosophila and humans alike (Bargiello et al., 1984; Siwicki et al., 1988; Hardin et al., 1990; Liu et al., 1992; Price et al., 1998). Circadian 24-h cellular mechanisms are genetic, evolutionarily conserved, and found across all photosensitive forms of life (Bass and Lazar, 2016). In the last 10 years circadian timing has been shown to have a direct impact on human disease, immunity, metabolism, and neurodegeneration (Man et al., 2016; Musiek and Holtzman, 2016; Panda, 2016; Turek, 2016).
Circadian timing can also have a direct impact on human LTM and learning. Circadian clocks are driven by complex genetic and neuroscientific processes. In turn these clocks co-ordinate most 24-h activity including physiological, metabolic, organ and brain functions, including wake/sleep and cognition. When circadian timing is disrupted, then the biological clocks in different tissues can become uncoupled, resulting in a state of internal desynchrony that can have negative impacts on memory creation and health (Foster et al., 2013). Here we consider the central role of modern societies in creating desynchrony when social and biological times are in conflict (Merton, 1936; Sorokin and Merton, 1937; Zerubavel, 1982, 1985; Foster et al., 2013).
There are many ways in which LTM can be created, though it is only recently that the neuron's intracellular synaptic plasticity mechanisms have been discovered in mice (Fields et al., 2005, Fields, 2005). In Fields' research these mechanisms required a “time code” of periods without stimuli to encode LTM. Specifically, the timing pattern was three stimuli separated by two 10-min periods without stimuli. Later, other researchers applied this timing pattern to humans learning complex bodies of structured information (Kelley and Whatson, 2013).
The first section explores recent advances in our understanding of circadian neuroscience, chronotypes, and sleep deprivation. These advances identify research-based applications for improving learning (and health) in adolescent education through synchronizing education times to circadian time. The second section focuses on advances in LTM neuroscience, and an application for improving learning based on these advances leading to creating LTM in humans of complex bodies of structured information. Both circadian and LTM neuroscience are then considered in memory consolidation in sleep.
Like most life on earth, our physiology, health and behaviors have 24-h rhythms that follow the increasing and decreasing light levels throughout the day and night. These changes in light are the most significant environmental time system and have led to a variety of biological systems to attune animals to circadian timing. In mammals, circadian timing is in effect a two-stage process, with cells individually generating a 24-h rhythm and a master circadian pacemaker establishing more consistent timing throughout the body. In humans the 24-h pacemaker is the suprachiasmatic nuclei (SCN) in the hypothalamus, and the SCN itself is synchronized, or “entrained,” to the variations in light, specifically irradiance. The specific biological mechanism for sensing these changes are triggered when blue light of ~480 nm wavelength enters the eye and strikes photosensitive retinal ganglion cells (pRGC) (Foster and Hankins, 2007). Generally, humans respond most strongly to light levels in twilight (before dawn or after sunset) that entrain circadian timing to the 24-h day.
This pRGC/SCN timing mechanism was discovered in mammals only recently and has implications for human functions including making memories. As circadian time systems adjust physiology and behavior in preparation for expected requirements during the day-night cycle, synchronization to changes in light are critical. Even sensing a single photon of light can be important: the absorption of a ~480 nm wavelength photon by 11-cis-retinaldehyde and the photoisomerization of this molecule in a pRGC leads to a strong signal being sent from the eye directly to the SCN (Wald, 1968; Foster and Hankins, 2007). The number of pRGC cells in the eye is relatively low, and consequently our sense of time depends on the gross amount of light of the appropriate wave length (Lucas et al., 2014). Changing levels of illuminance directly regulate pRGC activity and thus the SCN, creating an automatic, unconscious circadian time system. Indeed, totally blind subjects can retain normal circadian time function, demonstrating the separation of vision and time functions in the human eye (Zaidi et al., 2007).
Socially created lighting environments can also negatively impact on making memories as light itself has an important role in securing optimal physical and cognitive performance (Cajochen, 2007). Light has a direct impact on important aspects of creating memory: light levels act as a neurophysiological stimulant that increases alertness, attention, and improves reaction times. The direct response to bright light has differing impacts depending on the time as has been demonstrated in several ingenious studies (Cajochen et al., 2000; Phipps-Nelson et al., 2003; Rüger et al., 2006). While sunlight and very high light levels can boost human alertness, attention, cognition, and performance, low light levels can have the reverse effect (Lockley and Gooley, 2006; Lockley et al., 2006). For example, Rüger and colleagues concluded light levels may have a wide range of applications, ranging from optimizing a work environment to treating depressed patients. In contrast, many work environments rely on artificial light, reducing light levels far below the lux level of natural light, lowering light-induced alertness, and decreasing access to light with appropriately timed changes in illuminance that are critical in the pRGC/SCN timing system. The overall impact in schools, universities and employment is creating a more uniform, lower light experience throughout the day and increasing light at night, and this may have many direct and indirect impacts. In comparison to natural light levels many artificial light environments can negatively impact on natural circadian timing and health (Chang et al., 2015).
Although modern social behaviors, artificial light, and many other factors may cause individuals to become desynchronized from their circadian timing system, our research team found the most significant chronic desynchronization arises from the introduction of socially determined time or universal time (UTC), and fixed times for education, work and other activities. In order to measure desynchronization caused by UTC, our research team developed a new method of measuring time. We reasoned that UTC uses socially determined time zones, daylight savings time, and discounts changes in illuminance within time zones. In contrast, changes in light depend only on geophysical location and the pRGC/SCN timing mechanism, leading us to measure biological time as Geophysical Biological Time (GBT). GBT uses only the environmental cues of changing light in a specific geophysical location to calculate biological time and determining optimal timings for human activities (Bass and Lazar, Category :attorney