The gut microbiome regulates the increases in depressive-type behaviors and in inflammatory processes in the ventral hippocampus of stress vulnerable rats.

Chronic exposure to stress is associated with increased incidence of depression, generalized anxiety, and PTSD. However, stress induces vulnerability to such disorders only in a sub-population of individuals, as others remain resilient. Inflammation has emerged as a putative mechanism for promoting stress vulnerability. Using a rodent model of social defeat, we have previously shown that rats with short-defeat latencies (SL/vulnerable rats) show increased anxiety- and depression-like behaviors, and these behaviors are mediated by inflammation in the ventral hippocampus. The other half of socially defeated rats show long-latencies to defeat (LL/resilient) and are similar to controls. Because gut microbiota are important activators of inflammatory substances, we assessed the role of the gut microbiome in mediating vulnerability to repeated social defeat stress. We analyzed the fecal microbiome of control, SL/vulnerable, and LL/resilient rats using shotgun metagenome sequencing and observed increased expression of immune-modulating microbiota, such as Clostridia, in SL/vulnerable rats. We then tested the importance of gut microbiota to the SL/vulnerable phenotype. In otherwise naive rats treated with microbiota from SL/vulnerable rats, there was higher microglial density and IL-1ß expression in the vHPC, and higher depression-like behaviors relative to rats that received microbiota from LL/resilient rats, non-stressed control rats, or vehicle-treated rats. However, anxiety-like behavior during social interaction was not altered by transplant of the microbiome of SL/vulnerable rats into non-stressed rats. Taken together, the results suggest the gut microbiome contributes to the depression-like behavior and inflammatory processes in the vHPC of stress vulnerable individuals.

Changes in Female Drosophila Sleep following Mating Are Mediated by SPSN-SAG Neurons.

Female Drosophila melanogaster, like many other organisms, exhibit different behavioral repertoires after mating with a male. These postmating responses (PMRs) include increased egg production and laying, increased rejection behavior (avoiding further male advances), decreased longevity, altered gustation and decreased sleep. Sex Peptide (SP), a protein transferred from the male during copulation, is largely responsible for many of these behavioral responses, and acts through a specific circuit to induce rejection behavior and alter dietary preference. However, less is known about the mechanisms and neurons that influence sleep in mated females. In this study, we investigated postmating changes in female sleep across strains and ages and on different media, and report that these changes are robust and relatively consistent under a variety of conditions. We find that female sleep is reduced by male-derived SP acting through the canonical sex peptide receptor (SPR) within the same neurons responsible for altering other PMRs. This circuit includes the SPSN-SAG neurons, whose silencing by DREADD induces postmating behaviors including sleep. Our data are consistent with the idea that mating status is communicated to the central brain through a common circuit that diverges in higher brain centers to modify a collection of postmating sensorimotor processes.

The Drosophila Circadian Clock Gates Sleep through Time-of-Day Dependent Modulation of Sleep-Promoting Neurons.

STUDY OBJECTIVES: Sleep is under the control of homeostatic and circadian processes, which interact to determine sleep timing and duration, but the mechanisms through which the circadian system modulates sleep are largely unknown. We therefore used adult-specific, temporally controlled neuronal activation and inhibition to identify an interaction between the circadian clock and a novel population of sleep-promoting neurons in Drosophila. METHODS: Transgenic flies expressed either dTRPA1, a neuronal activator, or Shibire(ts1), an inhibitor of synaptic release, in small subsets of neurons. Sleep, as determined by activity monitoring and video tracking, was assessed before and after temperature-induced activation or inhibition using these effector molecules. We compared the effect of these manipulations in control flies and in mutant flies that lacked components of the molecular circadian clock. RESULTS: Adult-specific activation or inhibition of a population of neurons that projects to the sleep-promoting dorsal Fan-Shaped Body resulted in bidirectional control over sleep. Interestingly, the magnitude of the sleep changes were time-of-day dependent. Activation of sleep-promoting neurons was maximally effective during the middle of the day and night, and was relatively ineffective during the day-to-night and night-to-day transitions. These time-ofday specific effects were absent in flies that lacked functional circadian clocks. CONCLUSIONS: We conclude that the circadian system functions to gate sleep through active inhibition at specific times of day. These data identify a mechanism through which the circadian system prevents premature sleep onset in the late evening, when homeostatic sleep drive is high.