HDAC6 Regulates Glucocorticoid Receptor Signaling in Serotonin Pathways with Critical Impact on Stress Resilience

Genetic variations in certain components of the glucocorticoid receptor (GR) chaperone complex have been associated with the development of stress-related affective disorders and individual variability in therapeutic responses to antidepressants. Mechanisms that link GR chaperoning and stress susceptibility are not well understood. Here, we show that the effects of glucocorticoid hormones on socioaffective behaviors are critically regulated via reversible acetylation of Hsp90, a key component of the GR chaperone complex. We provide pharmacological and genetic evidence indicating that the cytoplasmic lysine deacetylase HDAC6 controls Hsp90 acetylation in the brain, and thereby modulates Hsp90–GR protein–protein interactions, as well as hormone- and stress-induced GR translocation, with a critical impact on GR downstream signaling and behavior. Pet1-Cre-driven deletion of HDAC6 in serotonin neurons, the densest HDAC6-expressing cell group in the mouse brain, dramatically reduced acute anxiogenic effects of the glucocorticoid hormone corticosterone in the open-field, elevated plus maze, and social interaction tests. Serotonin-selective depletion of HDAC6 also blocked the expression of social avoidance in mice exposed to chronic social defeat and concurrently prevented the electrophysiological and morphological changes induced, in serotonin neurons, by this murine model of traumatic stress. Together, these results identify HDAC6 inhibition as a potential new strategy for proresilience and antidepressant interventions through regulation of the Hsp90–GR heterocomplex and focal prevention of GR signaling in serotonin pathways. Our data thus uncover an alternate mechanism by which pan-HDAC inhibitors may regulate stress-related behaviors independently of their action on histones

Proceedings of the 13th annual conference of INEBRIA

CITATION: Watson, R., et al. 2016. Proceedings of the 13th annual conference of INEBRIA. Addiction Science & Clinical Practice, 11:13, doi:10.1186/s13722-016-0062-9.The original publication is available at https://ascpjournal.biomedcentral.comENGLISH SUMMARY : Meeting abstracts.https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-016-0062-9Publisher's versio

Data from: Electricity and water conservation on college and university campuses in response to national competitions among dormitories: quantifying relationships between behavior, conservation strategies and psychological metrics

“Campus Conservation Nationals” (CCN) is a recurring, nation-wide electricity and water-use reduction competition among dormitories on college campuses. We conducted a two year empirical study of the competition’s effects on resource consumption and the relationship between conservation, use of web technology and various psychological measures. Significant reductions in electricity and water use occurred during the two CCN competitions examined (n = 105,000 and 197,000 participating dorm residents respectively). In 2010, overall reductions during the competition were 4% for electricity and 6% for water. The top 10% of dorms achieved 28% and 36% reductions in electricity and water respectively. Participation was larger in 2012 and reductions were slightly smaller (i.e. 3% electricity). The fact that no seasonal pattern in electricity use was evident during non-competition periods suggests that results are attributable to the competition. Post competition resource use data collected in 2012 indicates that conservation behavior was sustained beyond the competition. Surveys were used to assess psychological and behavioral responses (n = 2,900 and 2,600 in 2010 and 2012 respectively). Electricity reductions were significantly correlated with: web visitation, specific conservation behaviors, awareness of the competition, motivation and sense of empowerment. However, participants were significantly more motivated than empowered. Perceived benefits of conservation were skewed towards global and future concerns while perceived barriers tended to be local. Results also suggest that competitions may be useful for “preaching beyond the choir” – engaging those who might lack prior intrinsic or political motivation. Although college life is distinct, certain conclusions related to competitions, self-efficacy, and motivation and social norms likely extend to other residential settings

Anatomically and functionally distinct thalamocortical inputs to primary and secondary mouse whisker somatosensory cortices

Subdivisions of mouse whisker somatosensory thalamus project to cortex in a region-specific and layer-specific manner. However, a clear anatomical dissection of these pathways and their functional properties during whisker sensation is lacking. Here, we use anterograde trans-synaptic viral vectors to identify three specific thalamic subpopulations based on their connectivity with brainstem. The principal trigeminal nucleus innervates ventral posterior medial thalamus, which conveys whisker-selective tactile information to layer 4 primary somatosensory cortex that is highly sensitive to self-initiated movements. The spinal trigeminal nucleus innervates a rostral part of the posterior medial (POm) thalamus, signaling whisker-selective sensory information, as well as decision-related information during a goal-directed behavior, to layer 4 secondary somatosensory cortex. A caudal part of the POm, which apparently does not receive brainstem input, innervates layer 1 and 5A, responding with little whisker selectivity, but showing decision-related modulation. Our results suggest the existence of complementary segregated information streams to somatosensory cortices. The thalamus provides sensory input to the cortex, but many aspects of thalamocortical signaling remain unknown. Here, the authors reveal parallel non-overlapping thalamic pathways with distinct representations of tactile and decision-related information during a goal-directed sensorimotor task

Spring 2012 CCN data with psychological variables

This data file contains data at the dorm level collected from our online survey and merged with the resource use data. The first sheet contains metadata defining all variable names

Fall 10 CCN data aggregated at dorm level with psychological variables

This data file contains data at the dorm level collected from our online survey and merged with the resource use data. The first sheet contains metadata defining all variable names

Fall 10 Campus Conservation Nationals electricity, water, webhit, and commitment data

This data file contains data at the dorm level collected by Lucid before, during, and after the Fall 2010 CCN competition. The first sheet contains metadata defining all variable names

Spring 2012 Campus Conservation Nationals survey

This online survey was administered to students attending colleges who participated in the Spring 2012 Campus Conservation Nationals competition. Not all schools who participated in the competition administered the survey

Fall 2010 Campus Conservation Nationals survey

This online survey was administered to students attending colleges who participated in the Fall 2010 Campus Conservation Nationals competition. Not all schools who participated in the competition administered the survey

Spring 2012 Campus Conservation Nationals electricity, water, and commitment data

This data file contains data at the dorm level collected by Lucid before, during, and after the Spring 2012 CCN competition. The first sheet contains metadata defining all variable names