Cartilage in the brain morphs while we sleep – possibly explaining why a good snooze can help consolidate memories, a new study suggests.
The neurons in our brains that exchange information and help us learn have a cartilage-like sheath around them, known as a perineuronal net (PNN).
US researchers believe that sleeping loosens this net enough to make our strong memories stronger and our weak memories weaker, causing them to drop out.
Using mice and brains from human donors, they worked out PNNs densities in brain regions involved in emotional memory processing during a day’s body cycle.
They found that PNNs change in their elasticity in a circadian manner – recurring naturally on a 24-hour cycle – but sleep deprivation can disrupt this cycle.
This suggests sleep deprivation disrupts the natural process of memory consolidation by having the opposite effect – essentially strengthening these nets.
Manipulating PNNs could help people avoid post-traumatic stress disorder (PTSD), by preventing distressing events from entering the long-term memory.
A perineuronal net, or PNN (shown in red) in the mouse brain, surrounding a neuron expressing Arc (green) – a protein involved in memory processing. The holes in the PNN may represent sites of memory storage that are regulated during sleep
‘Our results demonstrate that PNNs vary in a circadian manner and this is disrupted by sleep deprivation,’ say the researchers in the journal eNeuro.
‘We suggest that rhythmic modification of PNNs may contribute to memory consolidation during sleep.’
Sleep provides an opportunity for the human body to rest – except for the brain.
During sleep, the brain accounts for a day of learning by making strong memories stronger and weak memories weaker – a process known as memory consolidation.
Memory consolidation is a time-dependent process by which new-found knowledge and recent experiences are turned into long-term memories.
But changing memories requires changing synapses, the junctions through which information flows between neurons.
During REM sleep – the fourth stage of sleep, associated with vivid dreams – synapses are thought to undergo modification as memory consolidation processes occur.
However, sleep-induced changes need to overcome the cartilage-like sheaths known as PNNs.
PNNs not only surround and protect neurons but also prevent changes in synapses.
Although PNNs have been historically considered stable structures, recent studies suggest they are modified during learning to allow for formation of synapses.
The research team, led by scientists at University of Mississippi Medical Center, therefore theorised that PNNs vary during sleep, which they define as ‘a period of active synaptic modification’.
Changing memories requires changing synapses, the connections between neurons, shown here in an artist’s impression. Sleep-induced changes need to overcome PNNs, cartilage-like sheaths that not only surround and protect neurons, but also prevent changes in synapses
In the lab, mice were sleep deprived, euthanised and then had sections of their brain dissected for study.
By documenting whether or not they could tag the nets with a protein that binds to a specific sugar chain, they were able to observe the changes in synapses.
A decrease in the number of tagged nets would indicate an increase in the number of neurons allowing synaptic changes.
The team found that tagging increased during wakefulness and decreased during sleep – although sleep deprivation prevented this change.
This demonstrates that a lack of sleep during the night disrupts circadian rhythm, lowers the number of neurons allowing synaptic changes, and therefore puts a halt to memory consolidation.
Circadian rhythms in mammals are a natural, internal process that regulates the sleep-wake cycle independent of light and dark – which explains why we get jetlag.
‘Our data adds to a growing number of studies demonstrating that PNNs are dynamic structures, responding to the environment and potentially contributing to memory consolidation during sleep,’ the team say.
‘PNN rhythmicity occurs in mice kept in constant darkness, supporting the claim that these changes reflect circadian rhythms rather than a response to light-dark cycles.’
The research team also compared levels of tagged nets in human brain tissue obtained from the Harvard Brain Tissue Resource Center in Massachusetts with each donor’s time of death.
Human postmortem studies have successfully used time of death as a proxy for circadian rhythms in the human brain, providing a snapshot of activity.
They found that human brains displayed similar sleep-centric rhythms in net structure to mice, and suggest that altering the structure of PNNs may be one of the mechanisms behind sleep-induced memory changes.
Circadian rhythms of PNNs in human subjects have ‘broad implications’ for psychiatric disorders.
PNN deficits have been reported in the amygdala, entorhinal cortex, hippocampus, prefrontal cortex, and TRN in schizophrenia and bipolar disorder patients.
Disruption of PNNs in these disorders may alter rhythms of synaptic plasticity and in turn contribute to synaptic deficits.
Sleep deprivation has also been proposed as an early therapeutic approach for PTSD following a traumatic experience.
It’s possible that disrupting molecular processes involved in PNN rhythms, via sleep deprivation, could alleviate the strength of fear memories contributing to PTSD.