Anesthetics rapidly promote synaptogenesis during a critical period of brain development

• Published in: PloS one Vol. 4; no. 9; p. e7043
• Main Authors: De Roo, Mathias, Klauser, Paul, Briner, Adrian, Nikonenko, Irina, Mendez, Pablo, Dayer, Alexandre, Kiss, Jozsef Z, Muller, Dominique, Vutskits, Laszlo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.09.2009; Public Library of Science (PLoS)
• Subjects: Anesthesia; Anesthesia, General; Anesthesiology; Anesthesiology and Pain Management/Anesthetic Mechanisms; Anesthetics; Anesthetics - pharmacology; Animals; Birth weight; Brain; Brain - drug effects; Brain - growth & development; Brain slice preparation; Child development; Circuits; Cortex (somatosensory); Critical period; Dendritic spines; Dendritic Spines - drug effects; Dendritic Spines - metabolism; Developmental Biology/Neurodevelopment; Drug development; Drugs; GABA; Glutamic acid receptors (ionotropic); Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Infants; Intensive care; Medicine; Mice; Microscopy, Confocal - methods; Modulators; Morphology; N-Methyl-D-aspartic acid receptors; Nervous system; Nervous System - growth & development; Nervous System Physiological Phenomena; Neuromodulation; Neurons; Neuroscience; Neurosciences; Pharmacology; Receptors; Rodents; Somatosensory Cortex - drug effects; Somatosensory Cortex - metabolism; Spine; Synapses; Synapses - metabolism; Synaptogenesis; Switzerland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0007043

Experience-driven activity plays an essential role in the development of brain circuitry during critical periods of early postnatal life, a process that depends upon a dynamic balance between excitatory and inhibitory signals. Since general anesthetics are powerful pharmacological modulators of neuronal activity, an important question is whether and how these drugs can affect the development of synaptic networks. To address this issue, we examined here the impact of anesthetics on synapse growth and dynamics. We show that exposure of young rodents to anesthetics that either enhance GABAergic inhibition or block NMDA receptors rapidly induce a significant increase in dendritic spine density in the somatosensory cortex and hippocampus. This effect is developmentally regulated; it is transient but lasts for several days and is also reproduced by selective antagonists of excitatory receptors. Analyses of spine dynamics in hippocampal slice cultures reveals that this effect is mediated through an increased rate of protrusions formation, a better stabilization of newly formed spines, and leads to the formation of functional synapses. Altogether, these findings point to anesthesia as an important modulator of spine dynamics in the developing brain and suggest the existence of a homeostatic process regulating spine formation as a function of neural activity. Importantly, they also raise concern about the potential impact of these drugs on human practice, when applied during critical periods of development in infants.