Anesthetics Rapidly Promote Synaptogenesis during a Critical Period of Brain Development

Mathias De Roo,Laszlo Vutskits,Pablo Mendez,Irina Nikonenko,Paul Klauser,Jozsef Z Kiss,Dominique Muller,Alexandre Dayer,Adrian Briner,Alain Chédotal

doi:10.1371/journal.pone.0007043

Mathias De Roo, Laszlo Vutskits + Show 8 more

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https://doi.org/10.1371/journal.pone.0007043

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Journal: PloS one	Publication Date: Sep 16, 2009
Citations: 196	License type: CC BY 4.0

Affiliation: University of Geneva, University Hospital of Geneva

Abstract

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.

Highlights

Formation, elimination and remodeling of excitatory synapses on dendritic spines are continuously active processes that shape the organization of synaptic networks during development
In mice that did not undergo anesthesia, we found, consistent with previous reports [21,22,23], that there was a significant increase in protrusion density on tufted apical dendrites of layer 5 pyramidal neurons of the somatosensory cortex (SSC) between postnatal day (PND) 15 and 30 (Fig. 1a, b)
The present study provides evidence that exposure to general anesthetics rapidly induces dendritic spine growth and the formation of functional synapses during critical periods of early postnatal life in the rodent brain

Summary

Introduction

Elimination and remodeling of excitatory synapses on dendritic spines are continuously active processes that shape the organization of synaptic networks during development. Accumulating experimental works demonstrate that, during critical periods of development, both environmental, genetic and pharmacological interference with physiological neuronal activity can markedly and permanently alter wiring patterns and, thereby, information processing in the central nervous system (CNS) [6,7,8]. An important parameter regulating these processes is the balance between excitation and inhibition [9]. Alteration of this balance through interference with the function of local inhibitory circuits determines the characteristics and spacing of input segregation for ocular dominance columns formation and controls the onset of critical periods by regulating perisomatic GABA responses [10,11,12]. Functional deficits in neurodevelopmental disorders, such as the Down and the Rett syndrome, or autism spectrum disorders have been proposed to be linked to a shift in the balance between excitation and inhibition in the CNS [14,15,16,17]

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