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.
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.
Salichon
N
N
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 146, Institut Curie, 91405 Orsay, France.
Gaspar
P
P
Upton
A L
AL
Picaud
S
S
Hanoun
N
N
Hamon
M
M
De Maeyer
E
E
Murphy
D L
DL
Mossner
R
R
Lesch
K P
KP
Hen
R
R
Seif
I
I
D000818:Animals; D001931:Brain Mapping; D002352:Carrier Proteins / Q000235:genetics; D003433:Crosses, Genetic; D005260:Female; D005829:Geniculate Bodies / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D026901:Membrane Transport Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000172:deficiency* / Q000235:genetics; D009043:Motor Activity / Q000235:genetics; D009069:Movement Disorders / Q000235:genetics* / Q000503:physiopathology; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins; D013003:Somatosensory Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013788:Thalamus / Q000166:cytology / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors; D014795:Visual Pathways / Q000378:metabolism
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D012701:Serotonin; D014365:Tryptophan Hydroxylase; D008995:Monoamine Oxidase