Lesion-induced sprouting promotes neurophysiological integration of septal and entorhinal inputs to granule cells in the dentate gyrus of rats.

Axonal sprouting of dentate gyrus (DG) afferents after entorhinal cortex (EC) lesion is a model preparation to assess lesion-induced functional reorganization in a denervated target structure. Following a unilateral EC lesion, the surviving contralateral entorhinal projection, termed the crossed temporodentate pathway (CTD), and the heterotypic septal input to the DG, the septodentate pathway (SD), undergo extensive axonal sprouting. We explored whether EC lesion alters the capacity of the SD pathway to influence CTD-evoked granule cell excitability in the DG. We recorded extracellular field excitatory postsynaptic potentials (fEPSPs) after CTD stimulation alone and paired SD-CTD stimulation. Male rats were given unilateral EC lesions or sham operations; evoked fEPSPs in the DG were recorded at 4-, 15-, and 90-days post-entorhinal lesion to assess functional reorganization of the CTD and SD pathways. We found significantly increased fEPSP amplitudes in cases with unilateral lesions compared to sham-operates at 15- and 90-days post lesion. Within each time point, paired SD-CTD stimulation resulted in significantly depressed fEPSP amplitudes compared to amplitudes evoked after CTD stimulation alone and this effect was solely seen in cases with EC lesion. In cases where granule cell discharge was observed, SD stimulation increased discharge amplitude elicited by the CTD stimulation at 90-days postlesion. These findings demonstrate that synaptic remodeling following unilateral cortical lesion results in a synergistic interaction between two established hippocampal afferents that is not seen in uninjured brains. This work may be important for models of neurodegenerative disease and neural injury that target these structures and associated hippocampal circuitry.

Racial disparities in sleep-related cardiac function in young, healthy adults: implications for cardiovascular-related health.

STUDY OBJECTIVES: Considerable evidence shows that individuals from marginalized racial/ethnic groups in the United States experience greater rates of sleep disturbance and cardiovascular complications. Because sleep is a modifiable factor that is critically involved in cardiovascular health, improved understanding of the association between sleep and cardiovascular health during early adulthood can prevent cardiovascular disparities. This study examined racial/ethnic differences in cardiovascular function during sleep using heart rate and heart-rate-variability analyses. METHODS: Participants in this laboratory-based sleep study included healthy, "good sleepers" who were in early adulthood and resided in the United States at the time of participation (14 non-Hispanic Black [NHB; age = 30.9 (6.6), 57% female], 12 Asian [Asian, age = 26.0 (5.2), 42% female], and 24 non-Hispanic white [NHW; age = 24.6 (5.8), 79% female]). RESULTS: After adjusting for demographic factors and an apnea-hypopnea index, we found significantly higher heart rate within NREM Stage 2 (N2) (b = -22.6, p = .04) and REM sleep (b = -25.8, p =.048) and lower heart rate variability during N2 sleep (b = -22.6, p = .04) among NHB individuals compared with NHW individuals. Furthermore, NHB and Asian participants demonstrated significantly lower percent of time in slow wave sleep (SWS) compared with NHW participants (NHB: b = -22.6, p =.04; Asian: b = -22.6, p = .04). Individuals' percent of time in SWS significantly mediated differences in heart rate during N2 (indirect = 0.94, 95% CI [0.03, 2.68]) and REM sleep (indirect = 1.02, 95% CI [0.04, 3.04]). CONCLUSIONS: Our results showed disparities in sleep-related cardiovascular function in early adulthood that are mediated by SWS. These data suggest targeting sleep health in early adulthood might help reduce cardiovascular disease burden on individuals from marginalized groups.

Experimental sleep disruption and reward learning: moderating role of positive affect responses.

STUDY OBJECTIVES: Sleep disturbances increase vulnerability for depression, but the mechanisms underlying this relationship are not well known. We investigated the effects of experimental sleep disruption on response bias (RB), a measure of reward learning previously linked to depression, and the moderating role of positive affect responses. METHODS: Participants (N = 42) were healthy adults enrolled in a within-subject crossover sleep disruption experiment that incorporated one night of uninterrupted sleep (US) and one night of forced awakenings (FA) in random order. On the day following each experimental sleep night, participants completed a probabilistic reward task to assess RB, and the Positive and Negative Affect Schedule-X. Participants were subgrouped according to positive affect responses: Preserved Positive Affect (i.e. positive affect scores maintained or increased; n = 15) or Reduced Positive Affect (i.e. positive affect scores decreased; n = 27) following FA. RESULTS: Contrary to our hypotheses, across participants, RB did not significantly differ between the US and FA sleep conditions (p = .67). However, the effect of sleep condition on RB was moderated by positive affect response (p = .01); those with preserved positive affect showed heightened RB following FA, whereas those with reduced positive affect showed diminished RB following FA. Changes in negative affect between US and FA did not moderate RB. CONCLUSION: The inability to preserve positive affect through periods of sleep disruption may be a marker of diminished reward learning capability. Understanding how sleep disruption impacts positive affect responses and reward learning identifies a pathway by which sleep disturbances may confer risk for depression.