Xylazine, a veterinary sedative now used recreationally with fentanyl, interacts with human serotonin 7 (5-HT7R) and kappa-opioid (KOR) receptors. Computational docking and molecular dynamics simulations identified binding motifs and showed that small structural changes can improve xylazine's affinity for these receptors. These findings may help explain xylazine's psychoactive effects and guide treatments for overdoses.
Sleep is a complex neurophysiological process. A new integrative framework proposes that REM sleep is a state where the brain constructs a provisional dummy model of the external world. NREM sleep is a phase of synaptic and network reorganization with glymphatic clearance, updating neural circuits based on waking experience. REM sleep then provides an internal testing ground to simulate reality and refine these updates. The framework distinguishes phasic and tonic REM states and involves subcortical networks like the Papez circuit and claustrum. A central prediction is that prediction errors during REM drive selective synaptic consolidation in subsequent NREM via hippocampal sharp-wave ripple-mediated feedback. Awakening occurs when global prediction error falls below a threshold, and total sleep duration should be proportional to the complexity of novel waking experience.