Early life sleep disruption alters glutamate and dendritic spines in prefrontal cortex and impairs cognitive flexibility in prairie voles

Early life sleep disruption potentiates lasting sex-specific changes in behavior in genetically vulnerable Shank3 heterozygous autism model mice

“…Here we show that early life sleep disruption interacts with genetic vulnerability in Shank3 WT/C heterozygous ASD model mice to drive lasting and sex-specific changes in behavior. This work adds to a growing body of work using drosophila, prairie voles, and mice, showing that sleep disruption during vulnerable periods of brain development drive long-lasting changes in brain function and behavior (7)(8)(9)(10). The broader implications of this work are that developmental sleep disruption commonly seen in ASD patients may contribute to other phenotypes in the condition.…”

“…In order to test whether developmental sleep disruption contributes to altered adult behavior in our Shank3 ASD model, we utilized the experimental early life sleep disruption (ELSD) paradigm recently established by Jones and colleagues (7, 9). In their recent publications Jones et al, exposed developing prairie voles to ELSD from P14-P21, using an automated method in which the home cage is placed on an orbital shaker, and sleep is regularly disturbed by agitation at 110 RPM for 10 seconds every 109 seconds (10 seconds on, 99 seconds off).…”

“…Here, we tested the lasting effects of this ELSD paradigm on WT and Shank3 WT/ΔC mice (littermates), reproducing the method described by Jones et al (7, 9)(see methods). To specifically investigate whether early life represents a unique period of vulnerability to sleep disruption, we also tested the effects of sleep disruption treatment delivered later in life from P56-P63, referred to as post-adolescent sleep disruption (PASD) (Fig.…”

“…We speculate that sleep disruption during this period interacts with underlying genetic vulnerability, negatively impacting synapse maturation in sensitive neural circuits. In support of this idea, Jones at al., have shown that ELSD treatment in prairie voles drives increased dendritic spine density of layer II/III pyramidal neurons in the pre-frontal cortex (9), indicating a lasting change in glutamatergic synapses. Whether similar changes are seen in Shank3 WT/ΔC heterozygous mice exposed to ELSD will need to be determined.…”

“…Recent studies using rodent or fruit fly models showed that early life sleep disruption results in altered cognitive and social behaviors in adults, often with a male bias, strongly suggesting that sleep disruption during development can contribute to lasting ASD relevant phenotypes (7)(8)(9)(10).…”