Anesthetics fragment hippocampal network activity, alter spine dynamics, and affect memory consolidation

• DOI: 10.1371/journal.pbio.3001146
• Publication Date: 2021-04-01T17:51:38Z
• Authors: Wei Yang; Mattia Chini; Jastyn A. Pöpplau; Andrey Formozov; Alexander Dieter; Patrick Piechocinski; Cynthia Rais; Fabio Morellini; Olaf Sporns; Ileana L. Hanganu...; J. Simon Wiegert
• Keywords: Male; Xylazine; 0301 basic medicine; QH301-705.5; Midazolam; Mice, Transgenic; Hippocampus; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals; Anesthesia; Biology (General); Anesthetics; Memory Consolidation; Memory Disorders; Isoflurane; Medetomidine; Spine; Electrophysiological Phenomena; 3. Good health; Fentanyl; Mice, Inbred C57BL; Female; Ketamine; Nerve Net; Research Article

General anesthesia is characterized by reversible loss of consciousness accompanied by transient amnesia. Yet, long-term memory impairment is an undesirable side effect. How different types of general anesthetics (GAs) affect the hippocampus, a brain region central to memory formation and consolidation, is poorly understood. Using extracellular recordings, chronic 2-photon imaging, and behavioral analysis, we monitor the effects of isoflurane (Iso), medetomidine/midazolam/fentanyl (MMF), and ketamine/xylazine (Keta/Xyl) on network activity and structural spine dynamics in the hippocampal CA1 area of adult mice. GAs robustly reduced spiking activity, decorrelated cellular ensembles, albeit with distinct activity signatures, and altered spine dynamics. CA1 network activity under all 3 anesthetics was different to natural sleep. Iso anesthesia most closely resembled unperturbed activity during wakefulness and sleep, and network alterations recovered more readily than with Keta/Xyl and MMF. Correspondingly, memory consolidation was impaired after exposure to Keta/Xyl and MMF, but not Iso. Thus, different anesthetics distinctly alter hippocampal network dynamics, synaptic connectivity, and memory consolidation, with implications for GA strategy appraisal in animal research and clinical settings.