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Previous Article | Next Article
The Journal of Neuroscience, February 1, 2001, 21(3):884-896
Excessive Activation of Serotonin (5-HT) 1B Receptors Disrupts the Formation of Sensory Maps in Monoamine Oxidase A and 5-HT Transporter Knock-Out Mice
Nathalie Salichon1, Patricia Gaspar2, A. Louise Upton2, Sandrine Picaud1, Naïma Hanoun3, Michel Hamon3, Edward De Maeyer1, Dennis L. Murphy4, Rainald Mössner5, Klaus Peter Lesch5, René Hen6, and Isabelle Seif1 1 Centre National de la Recherche Scientifique, Unité Mixte de Recherche 146, Institut Curie, 91405 Orsay, France, 2 Institut National de la Santé et de la Recherche Médicale (INSERM) U106, Hôpital de la Pitié-Salpêtrière, 75651 Paris, France, 3 INSERM U288, Hôpital de la Pitié-Salpêtrière, 75634 Paris, France, 4 Laboratory of Clinical Science, The National Institute of Mental Health, Bethesda, Maryland 20892, 5 Department of Psychiatry and Psychotherapy, University of Würzburg, 97080 Würzburg, Germany, and 6 Center for Neurobiology and Behavior, Columbia University, New York, New York 10032
Deficiency in the monoamine degradation enzyme monoamine oxidase A (MAOA) or prenatal exposure to the monoamine uptake inhibitor cocaine alters behavior in humans and rodents, but the mechanisms are unclear. In MAOA knock-out mice, inhibiting serotonin synthesis during development can prevent abnormal segregation of axons in the retinogeniculate and somatosensory thalamocortical systems. To investigate this effect, we crossed MAOA knock-outs with mice lacking the serotonin transporter 5-HTT or the 5-HT1B receptor, two molecules present in developing sensory projections. Segregation was abnormal in 5-HTT knock-outs and MAOA/5-HTT double knock-outs but was normalized in MAOA/5-HT1B double knock-outs and MAOA/5-HTT/5-HT1B triple knock-outs. This demonstrates that the 5-HT1B receptor is a key factor in abnormal segregation of sensory projections and suggests that serotonergic drugs represent a risk for the development of these projections. We also found that the 5-HT1B receptor has an adverse developmental impact on beam-walking behavior in MAOA knock-outs. Finally, because the 5-HT1B receptor inhibits glutamate release, our results suggest that visual and somatosensory projections must release glutamate for proper segregation.
Key words: 5-HT1B receptor; monoamine oxidase; serotonin transporter; activity-dependent development; retinal projections; dorsal lateral geniculate nucleus; thalamocortical; barrel field
Copyright © 2001 Society for Neuroscience 0270-6474/01/213884-13$05.00/0
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