No abstract

Exposure-based therapies help patients with post-traumatic stress disorder (PTSD) to extinguish conditioned fear of trauma reminders. However, controlled laboratory studies indicate that PTSD patients do not extinguish conditioned fear as well as healthy controls, and exposure therapy has high failure and dropout rates. The present study examined whether vagus nerve stimulation (VNS) augments extinction of conditioned fear and attenuates PTSD-like symptoms in an animal model of PTSD. To model PTSD, rats were subjected to a single prolonged stress (SPS) protocol, which consisted of restraint, forced swim, loss of consciousness, and 1 week of social isolation. Like PTSD patients, rats subjected to SPS show impaired extinction of conditioned fear. The SPS procedure was followed, 1 week later, by auditory fear conditioning (AFC) and extinction. VNS or sham stimulation was administered during half of the extinction days, and was paired with presentations of the conditioned stimulus. One week after completion of extinction training, rats were given a battery of behavioral tests to assess anxiety, arousal and avoidance. Results indicated that rats given SPS 1 week prior to AFC (PTSD model) failed to extinguish the freezing response after eleven consecutive days of extinction. Administration of VNS reversed the extinction impairment and attenuated reinstatement of the conditioned fear response. Delivery of VNS during extinction also eliminated the PTSD-like symptoms, such as anxiety, hyperarousal and social avoidance for more than 1 week after VNS treatment. These results provide evidence that extinction paired with VNS treatment can lead to remission of fear and improvements in PTSD-like symptoms. Taken together, these findings suggest that VNS may be an effective adjunct to exposure therapy for the treatment of PTSD.

BackgroundWe and others have previously shown that alterations in the mammalian gut microbiome are associated with diet, notably early life exposure to a maternal high fat diet (HFD). Here, we aimed to further these studies by examining alterations in the gut microbiome of juvenile Japanese macaques (Macaca fuscata) that were exposed to a maternal HFD, weaned onto a control diet, and later supplemented with a synbiotic comprised of psyllium seed and Enterococcus and Lactobacillus species.ResultsEighteen month old offspring (n = 7) of 36% HFD fed dams were fed a control (14% fat) diet post weaning, then were synbiotic supplemented for 75 days and longitudinal stool and serum samples were obtained. All stool samples were subjected to 16S rRNA metagenomic sequencing, and microbiome profiles and serum lipids and triglycerides were compared to untreated, healthy age matched and diet matched controls (n = 7). Overall, 16S-based metagenomic analysis revealed that supplementation exerted minimal alterations to the gut microbiome including transient increased abundance of Lactobacillus species and decreased abundance of few bacterial genera, including Faecalibacterium and Anaerovibrio. However, serum lipid analysis revealed significant decreases in triglycerides, cholesterol, and LDL (p < 0.05). Nevertheless, supplemented juveniles challenged 4 months later were not protected from HFD-induced gut dysbiosis.ConclusionsSynbiotic supplementation is temporally associated with alterations in the gut microbiome and host lipid profiles of juvenile Japanese macaques that were previously exposed to a maternal HFD. Despite these presumptive temporal benefits, a protective effect against later HFD-challenge gut dysbiosis was not observed.Electronic supplementary materialThe online version of this article (10.1186/s12866-018-1169-9) contains supplementary material, which is available to authorized users.

Neural circuit plasticity and sensory response dynamics depend on forming new synaptic connections. Despite recent advances toward understanding the consequences of circuit plasticity, the mechanisms driving circuit plasticity are unknown. Adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and circuit integration. We and others have shown that efficient adult-born neuron circuit integration hinges on presynaptic activity in the form of diverse signaling peptides. Here, we demonstrate a novel oxytocin-dependent mechanism of adult-born neuron synaptic maturation and circuit integration. We reveal spatial and temporal enrichment of oxytocin receptor expression within adult-born neurons in the murine olfactory bulb, with oxytocin receptor expression peaking during activity-dependent integration. Using viral labeling, confocal microscopy, and cell type-specific RNA-seq, we demonstrate that oxytocin receptor signaling promotes synaptic maturation of newly integrating adult-born neurons by regulating their morphological development and expression of mature synaptic AMPARs and other structural proteins.