SEX-SPECIFIC IMPACTS OF EARLY LIFE SLEEP DISRUPTION: ETHANOL SEEKING, SOCIAL INTERACTION, AND ANXIETY ARE DIFFERENTIALLY ALTERED IN ADOLESCENT PRAIRIE VOLES.

Early life sleep is important for neuronal development and maturation. Using the highly social prairie vole rodent model, we have previously reported that early-life sleep disruption (ELSD) during the pre-weaning period postnatal day (P)14 to 21 results in adult interference with social bonding and increases ethanol consumption following a stressor. Furthermore, we have reported increased parvalbumin expression and reduced glutamatergic neurotransmission in cortical regions in adult prairie voles that experienced this paradigm. To understand the impact of ELSD on the lifespan, examination of an earlier time in life is necessary. Thus, the aim of the present study was to examine the behavioral outcomes of ELSD on adolescent prairie voles. Here we hypothesized that anxiety and reward related behaviors, as measured by light/dark box, 2-bottle choice and social interactions, would be negatively impacted by ELSD in adolescent male and female prairie voles. Male ELSD voles were no different from control voles in measures of anxiety and ethanol preference or consumption, but affiliative social interactions were significantly reduced. ELSD differentially impacted female prairie voles, with increased anxiety-like behavior and reductions in ethanol consumption compared to Controls, but no impact on ethanol preference or social interactions. Together, these results suggest both male and female prairie voles experience differential changes to reward seeking behaviors, but only female prairie voles showed increases in anxiety-like behavior. These results further suggest that early-life sleep is critically important for neurotypical behaviors in adolescence, a time where reward-seeking and risky behaviors are adaptive for learning and promoting survival.

Early-life sleep disruption increases parvalbumin in primary somatosensory cortex and impairs social bonding in prairie voles.

Across mammals, juveniles sleep more than adults, with rapid eye movement (REM) sleep at a lifetime maximum early in life. One function of REM sleep may be to facilitate brain development of complex behaviors. Here, we applied 1 week of early-life sleep disruption (ELSD) in prairie voles (Microtus ochrogaster), a highly social rodent species that forms lifelong pair bonds. Electroencephalographic recordings from juvenile voles during ELSD revealed decreased REM sleep and reduced γ power compared to baseline. ELSD impaired pair bond formation and altered object preference in adulthood. Furthermore, ELSD increased GABAergic parvalbumin immunoreactivity in the primary somatosensory cortex in adulthood, a brain region relevant to both affected behaviors. We propose that, early in life, sleep is crucial for tuning inhibitory neural circuits and the development of species-typical affiliative social behavior.

Gait and Conditioned Fear Impairments in a Mouse Model of Comorbid TBI and PTSD.

STUDY OBJECTIVES: Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) commonly cooccur. Approaches to research and treatment of these disorders have been segregated, despite overlapping symptomology. We and others have hypothesized that comorbid TBI + PTSD generates worse symptoms than either condition alone. We present a mouse model of comorbid TBI + PTSD to further explore this condition. METHODS: A mouse model of TBI + PTSD was generated using the single prolonged stress (SPS) protocol in combination with the controlled cortical impact (CCI) protocol. This resulted in four experimental groups: control, TBI, PTSD, and TBI + PTSD. Behavioral phenotyping included gait analysis, contextual fear conditioning, acoustic startle response, and prepulse inhibition. RESULTS: Mice in the TBI + PTSD group showed a significantly impaired gait compared to their counterparts with TBI alone as well as control mice. Mice in the TBI + PTSD group showed significantly impaired contextual fear recall compared to controls. Prepulse inhibition testing revealed intact acoustic startle and auditory sensory gating. CONCLUSIONS: These results indicate that SPS paired with CCI in mice produces unique behavioral impairments in gait and fear recall that are not present in either condition alone. Further studies are underway to examine additional behavioral, physiological, and pathological phenotypes in this combined model of TBI + PTSD.