Recognizing why chronic stress causes only a subset of individuals to become depressed is critical to understanding depression on a basic level and, also, to developing treatments that increase resilience. Stress-induced alterations in the activity of reward-related brain regions, such as the nucleus accumbens (NAc), are linked to the pathophysiology of depression. However, it has been difficult to determine if differences in stress susceptibility are pre-existing or merely an effect of chronic stress. The NAc consists largely of medium spiny neurons (MSNs), distinguished by their predominant expression of either D1 or D2 dopamine receptors. Mice that develop depressive-like symptoms after chronic social defeat stress show distinct changes in the activity of these two cell subtypes. Until now it has not been possible to determine whether such effects are merely a consequence of stress or in fact precede stress and, thus, have utility in pre-identifying stress-susceptible individuals. The goal of this study was to define a cell-type specific signature of stress susceptibility and resilience. Using fiber photometry calcium imaging, we recorded calcium transients in NAc D1- and D2-MSNs in awake behaving mice and found that D1-MSN activity is a predictive marker of depression susceptibility: prior to stress, mice that will later become resilient had increased baseline D1- MSN activity, and increased calcium transients specific to social interaction. Differences in D2- MSN activity were not specific to social interaction. Our findings identify a pre-existing mechanism of stress-induced susceptibility, creating the potential to target preventative interventions to the most relevant populations.
We present constraints on cosmological parameters from the Pantheon+ analysis of 1701 light curves of 1550 distinct Type Ia supernovae (SNe Ia) ranging in redshift from z = 0.001 to 2.26. This work features an increased sample size, increased redshift span, and improved treatment of systematic uncertainties in comparison to the original Pantheon analysis and results in a factor of 2 improvement in cosmological constraining power. For a FlatΛCDM model, we find Ω M = 0.338 ± 0.018 from SNe Ia alone. For a Flatw 0 CDM model, we measure w 0 = −0.89 ± 0.13 from SNe Ia alone, H 0 = 72.86 +0.94 −1.06 km s −1 Mpc −1 when including the Cepheid host distances and covariance (SH0ES), and w 0 = −0.978 +0.024 −0.031 when combining the SN likelihood with constraints from the cosmic microwave background (CMB) and baryon acoustic oscillations (BAO); both w 0 values are consistent with a cosmological constant. We also present the most precise measurements to date on the evolution of dark energy in a Flatw 0 w a CDM universe, and measure w a = −0.4 +1.0 −1.8 from Pantheon+ alone, H 0 = 73.40 +0.99 −1.22 km s −1 Mpc −1 when including SH0ES, and w a = −0.65 +0.28 −0.32 when combining Pan-theon+ with CMB and BAO data. Finally, we find that systematic uncertainties in the use of SNe Ia along the distance ladder comprise less than one third of the total uncertainty in the measurement of H 0 and cannot explain the present "Hubble tension" between local measurements and early-Universe predictions from the cosmological model.
BACKGROUND: Stress is a major risk factor for depression, but not everyone responds to stress in the same way. Identifying why certain individuals are more susceptible is essential for targeted treatment and prevention. In rodents, nucleus accumbens (NAc) afferents from the ventral hippocampus (vHIP) are implicated in stress-induced susceptibility, but little is known about how this pathway might encode future vulnerability or specific behavioral phenotypes. METHODS: We used fiber photometry to record in vivo activity in vHIP-NAc afferents during tests of depressive-and anxiety-like behavior in male and female mice, both before and after a sex-specific chronic variable stress protocol, to probe relationships between prestress neural activity and behavior and potential predictors of poststress behavioral adaptation. Furthermore, we examined chronic variable stress-induced alterations in vHIP-NAc activity in vivo and used ex vivo slice electrophysiology to identify the mechanism of this change. RESULTS: We identified behavioral specificity of the vHIP-NAc pathway to anxiety-like and social interaction behavior. We also showed that this activity is broadly predictive of stress-induced susceptibility in both sexes, while prestress behavior is predictive only of anxiety-like behavior. We observed a stress-induced increase in in vivo vHIP-NAc activity coincident with an increase in spontaneous excitatory postsynaptic current frequency. CONCLUSIONS: We implicate vHIP-NAc in social interaction and anxiety-like behavior and identify markers of vulnerability in this neural signal, with elevated prestress vHIP-NAc activity predicting increased susceptibility across behavioral domains. Our findings indicate that individual differences in neural activity and behavior play a role in predetermining susceptibility to later stress, providing insight into mechanisms of vulnerability.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.