Sleep is critical for proper sensory and social development in young prairie voles, an affiliative and monogamous rodent species.

These data are the first to report the prevalence and association between sensory sensitivity and sleep disturbances in Veterans with TBI. These data also suggest that the underlying mechanism of the sleep-sensory relationship could be due in part to comorbid PTSD and autonomic nervous system hyperarousal.

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including bradykinesia, tremor, rigidity and sleep-wake disturbances (SWD). SWDs are one of the most frequent non-motor symptoms of PD, often preceding the onset of other symptoms and, despite growing interest in studying SWD in the context of PD, there is a lack of appropriate murine models. Some lines of evidence recently suggested that sleep deficits correlate with increased burden in neurodegenerative disease and that sleep might alleviate disease severity by increasing clearance of metabolites and proteins from interstitial space, which could prove beneficial in diseases with protein accumulation/aggregation as primary pathology. Methods: We performed EEG/EMG recordings in vesicular monoamine transporter 2 (VMAT2) deficient mice at age of 5 months. Afterwards, at age of 14 months we investigated whether sleep modulation by means of pharmacological sleep induction and chronic REM sleep restriction had an effect on alpha-synuclein accumulation in the brain of VMAT2 deficient mice and behavioral symptoms. Results: EEG/EMG recordings in VMAT2 deficient mice (n=6) and wild type (WT) littermates (n=7) at age of 5 months shows that VMAT2 deficient animals present SWD and EEG changes similar to those seen in PD, namely: increased arousal, decreased time spent in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep and lower sleep efficiency. Furthermore, our results suggest that alpha-synuclein burden was reduced in the sleep-induced (SI) group as compared to the untreated (Ctrl) group. However, we found sleep modulation not associated with improved motor ability, which probably indicates hypodopaminergia as the primary cause of the phenotype as opposed to synucleopathy. Conclusion: Overall, our results suggest that VMAT2 deficient mice present increased arousal and reduced sleep efficiency and that revers- We therefore evaluated longitudinal changes in sleep and drug response. Methods: Adult male mice (n=9 each genotype) underwent surgery for EEG/EMG electrodes and E-mitters. Baseline was recorded at 10 (absent from motor symptoms), 15 (mild), 20 (moderate), and 25 (severe) weeks of age. Sleep deprivation was performed for 6 hours after baseline. Three doses of ropinirole, a dopamine D2-like receptor agonist, were intraperitoneally administered before the light off at 13, 17, 21, and 25 week olds. Results: MitoPark mice showed an age-dependent decline of up to 40% in locomotion following a new environment, while there was no difference between control and MitoPark mice in spontaneous locomotion through 24 hours on baseline in all ages examined. MitoPark mice had normal amounts, and natural diurnal distributions, of wakefulness and sleep in the baseline by 20 weeks. Once motor symptoms severely exacerbated at 25 weeks, sleep fragmentation and a decrease in NREM sleep amount occurred during light period. There was no difference in the occurrence of REM without atonia at 25 weeks. MitoPark mice age-dependently showed more enhanced increases in locomotion at middle and high doses than controls for 3 hours...

Synaptic pruning within neurons in the brain during development allows for maintenance of proper neuronal connections and the elimination of aberrant ones. Rapid eye movement (REM) sleep is critical for pruning and maintaining new synapses formed during both development and learning. We hypothesize that disrupting REM sleep early in life will result in long lasting changes in synaptic density in cortical brain regions. The prefrontal cortex (PFC) is a late-maturing region that modulates higher order social and cognitive functions. Abnormally high dendritic spine density in the PFC is implicated in neurodevelopmental disorders such as autism spectrum disorder (ASD). Emerging research in our lab suggests that selectively suppressing REM sleep early in life in the socially monogamous prairie vole (Microtus ochrogaster) impairs social development and increases inhibitory interneurons in the PFC, consistent with ASD pathology. Using Golgi-Cox staining in adult prairie vole post-mortem tissue, we quantified dendritic spines in the prefrontal cortex in adult animals that underwent early life sleep disruption (ELSD). In males, ELSD increased spine density and decreased spine width selectively in the apical oblique distal (> 90 µm) segments of pyramidal neurons in prelimbic cortex layers II/III. Distal dendrites reflect long range inputs from further cortical and thalamic regions, suggesting that ELSD may lead to an impaired ability to integrate sensory information. Ongoing work will examine dendritic spine density and morphology earlier in development and in additional brain regions, including the primary somatosensory cortex and other layers of the PFC. Results from these studies will enhance our understanding of how modulation of sleep early in life contributes to the neuropathology of developmental disorders.