top of page

Neuroscience Breakthroughs Since Graduate School - Part 1: Sleep

Updated: Dec 21, 2022


Hippocampal Neurons

Behavioral neuroscience discoveries have proceeded at a rapid pace. This series highlights cutting-edge findings and explains their importance for neurofeedback providers and their clients. This initial installment focuses on sleep.

Sleep Architecture Overview


We can divide sleep into non-REM (NREM) sleep which contains three stages, and rapid eye movement (REM) sleep. Stage 3 sleep (NREM3), termed slow-wave sleep and REM sleep, are arguably the most crucial stages. Following total sleep deprivation, we spend more time in Stage 3 on night one and in REM on night two (Breedlove & Watson, 2020). Graphic retrieved from Healing Touch Diagnostics.


Sleep Study


An average night’s sleep contains 4-5 cycles, 90-110 minutes each. Adults spend about 20% of total sleep in REM. Early cycles contain more stage 3 slow wave sleep (SWS), while later cycles contain increasing amounts of REM sleep (Breedlove & Watson, 2020). The hormone hypocretin regulates the order of our sleep stages. Excessive hypocretin is associated with insomnia, whereas deficient hypocretin is observed in narcolepsy (Holm et al., 2022). Graphic of a typical night of young adult sleep © Oxford University Press.


Typical Night of Young Adult Sleep


Why Is SWS Important?


SWS performs four functions vital to brain health and performance: growth hormone release, glymphatic system waste removal, replenishing astrocyte glycogen stores, and consolidating memory.



Growth Hormone Release


The body releases most growth hormone (GH; somatotropin) during SWS in the first half of the night. GH promotes bodywide tissue growth and repair by influencing protein metabolism (Breedlove & Watson, 2020). Graphic by Smiley et al. (2019) retrieved from ResearchGate.



At age 60, we spend half the time in stage 3 compared with age 20. Stage 3 sleep disappears by age 90, and its loss may be associated with cognitive impairment. Patients diagnosed with senile dementia spend significantly less time in Stage 3 (Kondratova & Kondratova, 2012). Growth hormone loss due to sleep disruption and the progressive reduction in Stage 3 sleep may cause cognitive deficits. Graphic of elderly sleep © Oxford University Press.


Elderly Sleep


Glymphatic System Waste Removal


The human brain contains a recently-discovered glymphatic system. This astrocyte-controlled lymphatic system removes cellular debris, proteins, and wastes (Xie et al., 2013). The flushing of toxic substances may protect us from neurological disorders like Alzheimer’s (Breedlove & Watson, 2020). Jeff Illiff showed waste removal in mice brains during sleep in his excellent 2014 TED MED Talk, One More Reason to Get a Good Night's Sleep. However, the discovery of the glymphatic system contradicted his view that there are no lymphatic vessels in the brain.


In the diagram below: (1) cerebrospinal fluid (CSF) flows from the subarachnoid space to travel outside pulsing arteries, (2) CSF enters the brain via aquaporins and collects waste, and (3) CSF enters the perivascular space surrounding capillaries and is removed by venous circulation. Graphic adapted by Wostyn and Goddaer (2022).


Glymphatic system

Stage 3 sleep accelerates the glymphatic system’s clearance of β-amyloid (Holth et al., 2019), which is shown in orange. Graphic © The University of Chicago retrieved from Science Life Education & Research News. Immune cells in the brain play key role in relationship between gut microbes and beta-amyloid.


Beta-amyloid


β-amyloid may initiate a cascade that transforms tau protein into a highly toxic molecule (Zhang et al., 2020), shown in red. Image by Juan Gaertner. Retrieved from News-Medical.Net. Alzheimer's and its helper protein.


Beta-amyloid and tau


Replenishing Astrocyte Glycogen Stores


Astrocytes are star-shaped glial cells that comprise part of the protective blood-brain barrier (BBB). The human brain primarily stores the energy source glycogen in astrocytes (Öz et al., 2007). Astrocyte graphic © Kateryna Kon/Shutterstock.com.

Astrocyte with blood vessel

Due to generally reduced metabolic demand compared with waking, stage 3 sleep allows astrocytes to rebuild their energy reserves when demand from neurons is the lowest. Astrocytes release glycogen to neurons during peak activity when we are awake (Bellesi et al., 2018; Schummers et al., 2008).


Neurons convert glycogen to glucose. Glycolysis and oxidative phosphorylation transform glucose into ATP (Ashrafi & Ryan, 2017). ATP powers vital neuronal functions like the sodium-potassium pumps, which restore a neuron's membrane potential. Graphic © Designua/ Shutterstock.com.


Sodium-potassium pump



Consolidating Memory

NREM sleep helps to consolidate declarative memories, which are memories we can describe (Nishida & Walker, 2007). In contrast, sleep deprivation helps to create false memories (Marshall et al., 2006). Norepinephrine (NE) levels rise and fall every 30 seconds in the sleeping mouse brain. The peaks (high NE levels) are associated with more than 100 brief awakenings that may aid memory consolidation. The valleys (low NE levels) occur when they are asleep (Kjaerby et al., 2022). Memory consolidation during NREM sleep appears to involve replaying the pattern of

neuronal firing observed when learning a task (Euston et al., 2007).


Each NREM slow wave is a “courier” that moves “packets of information” between anatomical regions (Walker, 2018).


NREM slow waves transfer fragile short-term memories from temporary (hippocampal) to long-term (cortical) storage.



Ripples Contribute to Human Memory Consolidation


We store a memory's sensory elements in specialized areas (e.g., auditory and visual) that are distributed across the cortex. The brain may coordinate these widespread networks during sleep and waking through synchronized 90-Hz oscillations called ripples.


During waking, cortical ripples occur on local high-frequency activity peaks. During sleep, cortical ripples typically occur on the cortical down-to-upstate transition, often with 10- to 16-Hz cortical sleep spindles, and local unit firing patterns consistent with generation by pyramidal-interneuron feedback. We found that cortical ripples group cofiring within the window of spike-timing-dependent plasticity. These findings are consistent with cortical ripples contributing to memory consolidation during NREM in humans (Dickey et al., 2022).

Inferior parietal cortex ripples in the human brain during NREM and waking © PNAS.



NREM-REM Partnership


The consolidation process may also determine which synapses survive and which are pruned away. NREM sleep consolidates new information, and REM sleep integrates it with our experience. NREM sleep removes outdated synapses, while REM sleep strengthens necessary connections. Graphic © Christoph Burgstedt/Shutterstock.com.


synapses


Why Is REM Sleep Important?

Rapid eye movements during REM sleep track the dream imagery created by mouse brains (Senzai & Scanziani, 2022). Jagged sawtooth waves (STWs) during REM sleep may synchronize the replay of memories to consolidate them (Frauscher et al., 2020). Graphic © The Atlas of Adult Electroencephalography.


REM sleep revises autobiographical memories to reflect the previous day’s events (Walker, 2018). Below, oligodendrocytes mediate memory formation in the central nervous system (Fields, 2019).

Graphic © Juan Gaertner/Shutterstock.com.


Oligodendrocytes

The interaction between NREM and REM sleep remodels neural circuitry based on current priorities to efficiently manage our brain’s limited storage capacity (Walker, 2018).