Neuronal activity rapidly reprograms dendritic translation via eIF4G2:uORF binding.

Learning and memory require activity-induced changes in dendritic translation, but which mRNAs are involved and how they are regulated are unclear. In this study, to monitor how depolarization impacts local dendritic biology, we employed a dendritically targeted proximity labeling approach followed by crosslinking immunoprecipitation, ribosome profiling and mass spectrometry. Depolarization of primary cortical neurons with KCl or the glutamate agonist DHPG caused rapid reprogramming of dendritic protein expression, where changes in dendritic mRNAs and proteins are weakly correlated. For a subset of pre-localized messages, depolarization increased the translation of upstream open reading frames (uORFs) and their downstream coding sequences, enabling localized production of proteins involved in long-term potentiation, cell signaling and energy metabolism. This activity-dependent translation was accompanied by the phosphorylation and recruitment of the non-canonical translation initiation factor eIF4G2, and the translated uORFs were sufficient to confer depolarization-induced, eIF4G2-dependent translational control. These studies uncovered an unanticipated mechanism by which activity-dependent uORF translational control by eIF4G2 couples activity to local dendritic remodeling.

PTSD and depression severity are associated with cardiovascular disease symptoms in trauma-exposed women.

Background: Posttraumatic stress disorder (PTSD) and depression are associated with increased risk for cardiovascular disease (CVD), which is the leading cause of death and disability worldwide. Epidemiological studies have revealed these illnesses to be highly comorbid, particularly among women. In the current study, we explored associations between indices of cardiovascular health, PTSD, and depression among a sample of trauma-exposed individuals assigned female at birth.Methods: Participants were N = 49 individuals without CVD who reported lifetime Criterion A trauma exposure. Blood pressure (BP), heart rate (HR), and high-frequency heart rate variability (HF-HRV) were collected during a 5-minute resting period. Symptoms of CVD (e.g. extremity pain and swelling, shortness of breath), PTSD, and depression were assessed, along with an exploratory measure of anhedonia.Results: Trauma exposure was positively correlated with systolic BP (r = .32, p = .029) and diastolic BP (r = .30, p = .040). The number of reported CVD symptoms was positively correlated with symptoms of PTSD (r = .41, p = .004), depression (r = .40, p = .005) and anhedonia (r = .38, p = .007). CVD symptoms were also significantly associated with PTSD (ß = .41, t = 2.43, p = .023), depression (ß = .40, t = 2.76, p = .009), and anhedonia (ß = .38, t = 2.51, p = .017) after controlling for age and trauma exposure. These associations were not moderated by HF-HRV in our sample.Conclusions: Our results support the association between PTSD and depressive symptoms and worse cardiovascular functioning among an often-overlooked population that is particularly vulnerable to these illnesses. Future studies should investigate residual impacts of PTSD and depression treatment on CVD risk among trauma-exposed individuals, particularly women.

Trauma exposure and PTSD are associated with depression and cardiovascular disease (CVD) risk.We explored cardiovascular health, PTSD, and depression among 49 trauma-exposed individuals assigned female at birth.Trauma exposure positively correlated with blood pressure.CVD symptoms were positively correlated with PTSD, depression, and anhedonia.Associations were not moderated by heart rate variability.

Vagal control moderates the association between endothelial function and PTSD symptoms in women with T2DM.

Background: Individuals with posttraumatic stress disorder (PTSD) are more likely to present with metabolic diseases such as type-2 diabetes mellitus (T2DM), and cardiovascular dysfunction has been implicated in this link. These diseases disproportionately affect women and individuals exposed to chronic environmental stressors (e.g., community violence, poverty). We examined associations among PTSD, cardiovascular indices, and metabolic function in highly trauma-exposed Black women with T2DM. Methods: Participants (N = 80) were recruited for a follow-up study of stress and T2DM as part of the Grady Trauma Project. PTSD symptoms were assessed with the Clinician Administered PTSD Scale (CAPS-IV). Cardiovascular indices included heart rate (HR), blood pressure (BP), respiratory sinus arrhythmia (RSA), and endothelial function (assessed via flow-mediated dilation; FMD). An oral glucose tolerance test was used as an indicator of metabolic function. Results: Of the cardiovascular indices, only FMD was significantly associated with PTSD symptoms (CAPS Avoidance symptoms; ß = -0.37, p = .042), and glucose tolerance (ß = -0.44, p = .019), controlling for age and body mass index. The association between FMD and PTSD Avoidance was moderated by RSA such that the effect of FMD was only significant at low levels of RSA (simple slopes ß = -0.87, p = .004). Conclusions: Our results indicate that endothelial function is significantly related to PTSD and glucose tolerance, over and above other cardiovascular measures (HR, BP, RSA). Further, our results suggest that low RSA may be a risk factor for the link between poor endothelial function and PTSD in women with T2DM.

Barrel cortex plasticity after photothrombotic stroke involves potentiating responses of pre-existing circuits but not functional remapping to new circuits.

Recovery after stroke is thought to be mediated by adaptive circuit plasticity, whereby surviving neurons assume the roles of those that died. However, definitive longitudinal evidence of neurons changing their response selectivity after stroke is lacking. We sought to directly test whether such functional "remapping" occurs within mouse primary somatosensory cortex after a stroke that destroys the C1 barrel. Using in vivo calcium imaging to longitudinally record sensory-evoked activity under light anesthesia, we did not find any increase in the number of C1 whisker-responsive neurons in the adjacent, spared D3 barrel after stroke. To promote plasticity after stroke, we also plucked all whiskers except C1 (forced use therapy). This led to an increase in the reliability of sensory-evoked responses in C1 whisker-responsive neurons but did not increase the number of C1 whisker-responsive neurons in spared surround barrels over baseline levels. Our results argue against remapping of functionality after barrel cortex stroke, but support a circuit-based mechanism for how rehabilitation may improve recovery.