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

Anesthetics; Xylazine; Ketamine; Isoflurane; Medetomidine; Midazolam; Fentanyl; Anesthesia/adverse effects; Anesthetics/adverse effects; Anesthetics/pharmacology; Animals; Electrophysiological Phenomena/drug effects; Female; Fentanyl/adverse effects; Fentanyl/pharmacology; Hippocampus/cytology; Hippocampus/drug effects; Hippocampus/physiology; Isoflurane/adverse effects; Isoflurane/pharmacology; Ketamine/adverse effects; Ketamine/pharmacology; Male; Medetomidine/adverse effects; Medetomidine/pharmacology; Memory Consolidation/drug effects; Memory Disorders/chemically induced; Memory Disorders/pathology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Midazolam/adverse effects; Midazolam/pharmacology; Nerve Net/drug effects; Nerve Net/physiology; Spine/drug effects; Spine/physiology; Xylazine/adverse effects; Xylazine/pharmacology; Anesthesia; Electrophysiological Phenomena; Hippocampus; Memory Consolidation; Memory Disorders; Nerve Net; Spine; Neuroscience (all); Biochemistry, Genetics and Molecular Biology (all); Immunology and Microbiology (all); Agricultural and Biological Sciences (all)

Abstract :

[en] 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.

Disciplines :

Life sciences: Multidisciplinary, general & others

Author, co-author :

Yang, Wei ^✱; Research Group Synaptic Wiring and Information Processing, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Chini, Mattia ^✱; Institute of Developmental Neurophysiology, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Pöpplau, Jastyn A ; Institute of Developmental Neurophysiology, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Formozov, Andrey ; Research Group Synaptic Wiring and Information Processing, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Dieter, Alexander ; Research Group Synaptic Wiring and Information Processing, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Piechocinski, Patrick ; Research Group Synaptic Wiring and Information Processing, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Rais, Cynthia; Research Group Synaptic Wiring and Information Processing, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Morellini, Fabio; Research Group Behavioral Biology, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Sporns, Olaf; Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, United States of America ; Indiana University Network Science Institute, Indiana University, Bloomington, Indiana, United States of America

Hanganu-Opatz, Ileana L; Institute of Developmental Neurophysiology, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Wiegert, J Simon ; Research Group Synaptic Wiring and Information Processing, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

^✱ These authors have contributed equally to this work.

Language :

English

Title :

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

Publication date :

April 2021

Journal title :

PLoS Biology

ISSN :

1544-9173

eISSN :

1545-7885

Publisher :

Public Library of Science, United States

Volume :

Issue :

Pages :

e3001146

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://dx.plos.org/10.1371/journal.pbio.3001146

Funders :

DFG - Deutsche Forschungsgemeinschaft
ERC - European Research Council
DAAD - German Academic Exchange Service
CSC - Chinese Scholarship Council

Funding text :

This work was funded by the Deutsche Forschungsgemeinschaft (DFG, SPP1926, FOR2419/P6, SFB936/B8 to J.S.W., SPP 1665/Ha 4466/10-1/Ha4466/12-1, SFB 936/B5 to I.L.H.-O., SFB 936/B7 to F.M.), the European Research Council (ERC2016-StG-714762 to J.S.W., ERC-2015-CoG 681577 to I.L.H.-O.), the German Academic Exchange Service (DAAD, STG/19/ 5744091 to A.F.), and the Chinese Scholarship Council (CSC 201606210129 to W.Y.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Available on ORBi :

since 18 March 2026

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