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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-HT_1B receptor; monoamine oxidase; serotonin transporter; activity-dependent development; retinal projections; dorsal lateral geniculate nucleus; thalamocortical; barrel field

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Copyright © 2001 Society for Neuroscience  0270-6474/01/213884-13$05.00/0

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