Anesthetics and the hippocampus: synapses, ensembles and memory

General anesthesia reversibly induces loss of consciousness, which can be reached via administration of a large repertoire of chemically highly diverse drugs commonly referred to as general anesthetics. The molecular targets in the body and thus their modes of action vary widely and as a consequence, different types of anesthetics modulate different aspects of central nervous system function. Although a plethora of studies investigated the effects of different anesthetics on various aspects of nervous system function, the results are often difficult to interpret, because systematic comparisons are still scarce. Moreover, little is known about the long-term effects of different anesthetics on hippocampal spine dynamics and network activity in vivo. Using extracellular electrical recordings, 2-photon imaging of calcium dynamics and chronic imaging of spine morphology, we investigated how Ketamine/Xylazine (KX), Isoflurane/Buprenorphine (IB) and Medetomidine/Midazolam/Fentanyl (MMF) anesthesia affects both activity of cellular ensembles and spine dynamics in area CA1 of the mouse hippocampus in comparison to the awake state. All three anesthetic conditions showed distinct activity signatures and they differentially affected spine dynamics, with KX displaying the strongest phenotype. This was associated with impairment of episodic memory consolidation after exposure to KX-mediated anesthesia, but not IB- or MMF-mediated anesthesia. Thus, despite fulfilling the hallmarks of general anesthesia, different anesthetics distinctly alter hippocampal network dynamics, synaptic connectivity and memory consolidation.