RESUMO
Early-life sleep disruption (ELSD) has been shown to have long-lasting effects on social behaviour in adult prairie voles (Microtus ochrogaster), including impaired expression of pair bonding during partner preference testing. However, due to the limitations of manual behaviour tracking, the effects of ELSD across the time course of pair bonding have not yet been described, hindering our ability to trace mechanisms. Here, we used pose estimation to track prairie voles during opposite-sex cohabitation, the process leading to pair bonding. Male-female pairs were allowed to interact through a mesh divider in the home cage for 72 h, providing variables of body direction, distance-to-divider and locomotion speed. We found that control males displayed periodic patterns of body orientation towards females during cohabitation. In contrast, ELSD males showed reduced duration and ultradian periodicity of these body orientation behaviours towards females. Furthermore, in both sexes, ELSD altered spatial and temporal patterns of locomotion across the light/dark cycles of the 72 h recordings. This study allows a comprehensive behavioural assessment of the effects of ELSD on later life sociality and highlights subtle prairie vole behaviours. Our findings may shed light on neurodevelopmental disorders featuring sleep disruption and social deficits, such as autism spectrum disorders.
RESUMO
In mammals, sleep duration is highest in the early postnatal period of life and is critical for shaping neural circuits that control the development of complex behaviors. The prairie vole is a wild, highly social rodent that serves as a unique model for the study of complex, species-typical social behaviors. Previous work in our laboratory has found that early life sleep disruption (ELSD) in prairie voles during a sensitive window of postnatal development leads to long lasting changes in social and cognitive behaviors as well as structural changes in excitatory and inhibitory neural circuits in the brain. However, it is currently unknown how later sleep is impacted by ELSD, both shortly after ELSD and over the long term. Therefore, the aim of this study was to describe the effects of ELSD on later life sleep, compared to sleep in normally developing prairie voles. First, we conducted tethered electroencephalogram/electromyogram (EEG/EMG) recordings in juvenile prairie voles undergoing ELSD, compared to Control conditions. Second, we conducted 24 h of home cage tethered EEG/EMG recordings in either adolescent or adult male and female prairie voles that had previously undergone ELSD or Control conditions as juveniles. We found that, as adults, male ELSD prairie voles showed persistently lower REM sleep duration and female ELSD prairie voles showed persistently higher NREM sleep duration compared to Controls, but no other sleep parameters differed. We concluded that 1) persistent effects of ELSD on sleep into adulthood may contribute to the social and cognitive deficits observed in adult voles, and 2) sleep disruption early in life can influence later sleep patterns in adulthood.
RESUMO
Sleep is an essential component of development. Developmental sleep disruption (DSD) impacts brain maturation and has been associated with significant consequences on socio-emotional development. In humans, poor sleep during infancy and adolescence affects neurodevelopmental outcomes and may be a risk factor for the development of autism spectrum disorder (ASD) or other neuropsychiatric illness. Given the wide-reaching and enduring consequences of DSD, identifying underlying mechanisms is critical to best inform interventions with translational capacity. In rodents, studies have identified some mechanisms and neural circuits by which DSD causes later social, emotional, sensorimotor, and cognitive changes. However, these studies spanned methodological differences, including different developmental timepoints for both sleep disruption and testing, different DSD paradigms, and even different rodent species. In this scoping review on DSD in rodents, we synthesize these various studies into a cohesive framework to identify common neural mechanisms underlying DSD-induced dysfunction in brain and behavior. Ultimately, this review serves the goal to inform the generation of novel translational interventions for human developmental disorders featuring sleep disruption.
RESUMO
Recent increases in human longevity have been accompanied by a rise in the incidence of dementia, highlighting the need to preserve cognitive function in an aging population. A small percentage of individuals with pathological hallmarks of neurodegenerative disease are able to maintain normal cognition. Although the molecular mechanisms that govern this neuroprotection remain unknown, individuals that exhibit cognitive resilience (CgR) represent a unique source of therapeutic insight. For both humans and animal models, living in an enriched, cognitively stimulating environment is the most effective known inducer of CgR. To understand potential drivers of this phenomenon, we began by profiling the molecular changes that arise from environmental enrichment in mice, which led to the identification of MEF2 transcription factors (TFs). We next turned to repositories of human clinical and brain transcriptomic data, where we found that the MEF2 transcriptional network was overrepresented among genes that are most predictive of end-stage cognition. Through single-nucleus RNA sequencing of cortical tissue from resilient and nonresilient individuals, we further confirmed up-regulation of MEF2C in resilient individuals to a subpopulation of excitatory neurons. Last, to determine the causal impact of MEF2 on cognition in the context of neurodegeneration, we overexpressed Mef2a/c in the PS19 mouse model of tauopathy and found that this was sufficient to improve cognitive flexibility and reduce hyperexcitability. Overall, our findings reveal a previously unappreciated role for MEF2 TFs in promoting CgR, highlighting their potential as biomarkers or therapeutic targets for neurodegeneration and healthy aging.
