Early-life sleep disruption impairs subtle social behaviours in prairie voles: a pose-estimation study.

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.

Early life sleep disruption has long lasting, sex specific effects on later development of sleep in prairie voles.

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.

Development of highly sensitive, flexible dual L-glutamate and GABA microsensors for in vivo brain sensing.

Real-time tracking of neurotransmitter levels in vivo has been technically challenging due to the low spatiotemporal resolution of current methods. Since the imbalance of cortical excitation/inhibition (E:I) ratios are associated with a variety of neurological disorders, accurate monitoring of excitatory and inhibitory neurotransmitter levels is crucial for investigating the underlying neural mechanisms of these conditions. Specifically, levels of the excitatory neurotransmitter L-glutamate, and the inhibitory neurotransmitter GABA, are assumed to play critical roles in the E:I balance. Therefore, in this work, a flexible electrochemical microsensor is developed for real-time simultaneous detection of L-glutamate and GABA. The flexible polyimide substrate was used for easier handling during implantation and measurement, along with less brain damage. Further, by electrochemically depositing Pt-black nanostructures on the sensor's surface, the active surface area was enhanced for higher sensitivity. This dual neurotransmitter sensor probe was validated under various settings for its performance, including in vitro, ex vivo tests with glutamatergic neuronal cells and in vivo test with anesthetized rats. Additionally, the sensor's performance has been further investigated in terms of longevity and biocompatibility. Overall, our dual L-glutamate:GABA sensor microprobe has its unique features to enable accurate, real-time, and long-term monitoring of the E:I balance in vivo. Thus, this new tool should aid investigations of neural mechanisms of normal brain function and various neurological disorders.