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

PLoS Biol. 2021 Apr 1;19(4):e3001146. doi: 10.1371/journal.pbio.3001146. eCollection 2021 Apr.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Anesthetics
  • Xylazine
  • Ketamine
  • Isoflurane
  • Medetomidine
  • Midazolam
  • Fentanyl