Understanding the neural code of stress to control anhedonia.

Anhedonia, the diminished drive to seek, value, and learn about rewards, is a core feature of major depressive disorder. The neural underpinnings of anhedonia and how this emotional state drives behaviour remain unclear. Here we investigated the neural code of anhedonia by taking advantage of the fact that when mice are exposed to traumatic social stress, susceptible animals become socially withdrawn and anhedonic, whereas others remain resilient.

Role of RNA structural plasticity in modulating HIV-1 genome packaging and translation.

HIV-1 transcript function is controlled in part by twinned transcriptional start site usage, where 5' capped RNAs beginning with a single guanosine (1G) are preferentially packaged into progeny virions as genomic RNA (gRNA) whereas those beginning with three sequential guanosines (3G) are retained in cells as mRNAs. In 3G transcripts, one of the additional guanosines base pairs with a cytosine located within a conserved 5' polyA element, resulting in formation of an extended 5' polyA structure as opposed to the hairpin structure formed in 1G RNAs. To understand how this remodeling influences overall transcript function, we applied in vitro biophysical studies with in-cell genome packaging and competitive translation assays to native and 5' polyA mutant transcripts generated with promoters that differentially produce 1G or 3G RNAs.

Identifying and modulating neural signatures of stress susceptibility and resilience enables control of anhedonia.

Anhedonia is a core aspect of major depressive disorder. Traditionally viewed as a blunted emotional state in which individuals are unable to experience joy, anhedonia also diminishes the drive to seek rewards and the ability to value and learn about them .The neural underpinnings of anhedonia and how this emotional state drives related behavioral changes remain unclear.

Neural signatures of stress susceptibility and resilience in the amygdala-hippocampal network.

The neural dynamics that underlie divergent anhedonic responses to stress remain unclear. Here, we identified neuronal dynamics in an amygdala-hippocampal circuit that distinguish stress resilience and susceptibility. In a reward-choice task, basolateral amygdala (BLA) activity in resilient mice showed enhanced discrimination of upcoming reward choices.

Structural basis for transcriptional start site control of HIV-1 RNA fate.

Heterogeneous transcriptional start site usage by HIV-1 produces 5'-capped RNAs beginning with one, two, or three 5'-guanosines (1G, 2G, or 3G, respectively) that are either selected for packaging as genomes (1G) or retained in cells as translatable messenger RNAs (mRNAs) (2G and 3G). To understand how 5'-guanosine number influences fate, we probed the structures of capped HIV-1 leader RNAs by deuterium-edited nuclear magnetic resonance. The 1G transcript adopts a dimeric multihairpin structure that sequesters the cap, inhibits interactions with eukaryotic translation initiation factor 4E, and resists decapping.