Tuning arousal

The locus coeruleus (LC), a major source of noradrenaline in the brain, plays a crucial role in regulating arousal and behavior. Despite its known functions, the mechanisms that control LC activity, particularly the influence of local GABAergic (γ-aminobutyric acid-producing) neurons, remain poorly understood. In a study published in Nature, Luskin, Li et al. identified a heterogeneous population of peri-LC^GABA neurons that directly inhibit LC neurons, thereby modulating arousal and avoidance behaviors. Using optogenetic and chemogenetic approaches in mice, the authors demonstrated that activation of peri-LC^GABA neurons markedly suppresses arousal and exploration, whereas inhibiting them heightens anxiety-like and avoidance behaviors. They further revealed the molecular diversity of neuronal populations within both the peri-LC and LC regions by using single-nucleus and spatial transcriptomic analyses in behaving mice. Subsequent experiments uncovered distinct neural responses to various stimuli in specific neuropeptide-expressing subpopulations and implicated these subpopulations in modulating arousal and avoidance behaviors. Together, these findings highlight peri-LC^GABA neurons as key regulators of LC activity, linking them to arousal-related behaviors and suggesting potential therapeutic targets for neuropsychiatric disorders.

Original reference: Nature https://doi.org/10.1038/s41586-025-08952-w (2025)