Early life adversity shapes social subordination and cell type-specific transcriptomic patterning in the ventral hippocampus.

Adverse events in early life can modulate the response to additional stressors later in life and increase the risk of developing psychiatric disorders. The underlying molecular mechanisms responsible for these effects remain unclear. Here, we uncover that early life adversity (ELA) in mice leads to social subordination. Using single-cell RNA sequencing (scRNA-seq), we identified cell type-specific changes in the transcriptional state of glutamatergic and GABAergic neurons in the ventral hippocampus of ELA mice after exposure to acute social stress in adulthood. These findings were reflected by an alteration in excitatory and inhibitory synaptic transmission induced by ELA in response to acute social stress. Finally, enhancing the inhibitory network function through transient diazepam treatment during an early developmental sensitive period reversed the ELA-induced social subordination. Collectively, this study significantly advances our understanding of the molecular, physiological, and behavioral alterations induced by ELA, uncovering a previously unknown cell type-specific vulnerability to ELA.

Increasing resolution in stress neurobiology: from single cells to complex group behaviors.

Stress can have severe psychological and physiological consequences. Thus, inappropriate regulation of the stress response is linked to the etiology of mood and anxiety disorders. The generation and implementation of preclinical animal models represent valuable tools to explore and characterize the mechanisms underlying the pathophysiology of stress-related psychiatric disorders and the development of novel pharmacological strategies. In this commentary, we discuss the strengths and limitations of state-of-the-art molecular and computational advances employed in stress neurobiology research, with a focus on the ever-increasing spatiotemporal resolution in cell biology and behavioral science. Finally, we share our perspective on future directions in the fields of preclinical and human stress research.