The period of neurodevelopment extending from birth to roughly two years of age is one of frenetic, constant change. Neurons and synapses form, are organized, and are pruned. It is well known that sleep plays a fundamental role in these processes, and disruptions to sleep at this stage can be devastating to neurodevelopment and may be the cause of disorders like autism spectrum disorder (ASD).
Understanding the relation between sleep and neurodevelopment in early life is thus essential to understanding (and perhaps preventing) developmental disorders. Building on previous work with prairie voles—a highly social animal with neurodevelopmental similarities to humans—researchers from Portland and California recently published a paper in Current Research in Neurobiology examining the effects of early life sleep disruptions (ELSD) on the prefrontal cortex (PFC).
The prefrontal cortex plays an important role in higher-order social learning, executive function, and cognitive flexibility. It’s also one of the last brain structures to mature, and is thus particularly sensitive to disruptions in development.
In the study, male and female prairie voles were either subject or not to ELSD from 14 to 21 days of age. This period roughly corresponds to the first and second years of human neurodevelopment. The authors then tested the voles for reduced cognitive flexibility and related disruptions in synaptic structures in the prefrontal cortex.
To test cognitive flexibility, the authors subjected voles to fear conditioning, applying a light electric shock through the floor in association with a sound (acquisition phrase). Then, in a separate session, the sound was played repeatedly without shock (extinction phrase). The more quickly a subject is able to adjust its response to the sound, the greater its cognitive flexibility.
The results of the study confirmed the authors hypothesis, in that voles subject to ELSD were less able to change their behavior following the “extinction” phase. That is, while control voles froze (a fear response) less and less frequently as they learned that the sound no longer predicted a shock, ELSD voles continued to freeze in anticipation. Importantly, both groups froze at similar levels during acquisition, meaning they acquired information equally well, but could not adapt it to the same degree.
As in humans, cognitive flexibility in voles relies on the prefrontal cortex. Neurodevelopmentally, the authors found significantly more dendritic spines in the PFC of ELSD voles, compared to the control group. The spines were also much thinner, which is a sign of underdevelopment. Dendritic spines are small protrusions on dendrites, the “receiving” part of a neuron, where other neurons connect via the synapse.
Both greater numbers of dendritic spines and their malformation can both result in cognitive and behavioral disorders. Indeed, neurodevelopmental disorders like ASD, also characterized by cognitive inflexibility, show similar neurophysiological malformations.
The mechanism by which sleep disruption impedes neurodevelopment, however, is still not well understood. It may be that increased wakefulness due to sleep disruption increases glutamate circulation in the brain, affecting glutamatergic structures. Alternatively, decreased REM sleep may reduce “pruning”, an essential developmental process in which superfluous synapses are removed to improve signaling and organization.
The authors note a few limitations, including the limited timespan of the study. Future work, they suggest, should examine ELSD at different points in time and for different durations. And, of course, any lessons learned from animal studies should be considered in light of all the developmental and neurological differences between subjects and humans.
Neurodevelopmental disorders are among the most difficult to diagnose, treat, and understand. Animal models provide an important opportunity, especially where developmental and cognitive correlates exist, as they do in voles and humans. It seems clear that sleep plays a critical role in the development of the prefrontal cortex. Furthering our knowledge of that role will lead to more effective interventions.
The study, “Early life sleep disruption alters glutamate and dendritic spines in prefrontal cortex and impairs cognitive flexibility in prairie voles”, was authored by Carolyn E. Jones et al and published July 10, 2021.
