PT  - JOURNAL ARTICLE
AU  - Tania Vitalis
AU  - Olivier Cases
AU  - Katy Gillies
AU  - Naima Hanoun
AU  - Michel Hamon
AU  - Isabelle Seif
AU  - Patricia Gaspar
AU  - Peter Kind
AU  - David J. Price
TI  - Interactions between TrkB Signaling and Serotonin Excess in the Developing Murine Somatosensory Cortex: A Role in Tangential and Radial Organization of Thalamocortical Axons
AID  - 10.1523/JNEUROSCI.22-12-04987.2002
DP  - 2002 Jun 15
TA  - The Journal of Neuroscience
PG  - 4987--5000
VI  - 22
IP  - 12
4099  - http://www.jneurosci.org/content/22/12/4987.short
4100  - http://www.jneurosci.org/content/22/12/4987.full
SO  - J. Neurosci.2002 Jun 15; 22
AB  - Mice lacking monoamine oxidase A (MAOA) display high levels of brain serotonin during the first postnatal week, causing an exuberant outgrowth of thalamocortical axons (TCAs) in layer IV of the somatosensory cortex (S1). We asked whether this exuberance is attributable to abnormal TrkB signaling, because modulation of TrkB signaling during a critical period dramatically influences the segregation and the morphology of TCAs in layer IV of the visual cortex. Using in situ hybridization and ELISA immunoassays, we showed that the levels of trkB mRNA and BDNF and neurotrophin-4 (NT-4) proteins are normal in the thalamus and the cortex of mice lacking MAOA during barrel field formation. Because the release of BDNF and NT-4 could be abnormal in MAOA knock-out (KO) mice, we tested whether abnormal TrkB signaling is required for TCA exuberance in MAOA-KO mice by generating mice lacking both trkB and MAOA. Surprisingly, these mice exhibited more severe phenotypes than those found in MAOA-KO mice: a widespread tangential expansion of TCAs in layer IV of the cortex, resulting in a fusion of all sensory representations and a radial expansion of TCAs in layers II–III of the cortex. Careful examination of mice lacking trkB alone revealed subtle alterations of TCAs, with abnormal invasion of layer III. This study reveals the following: (1) expression of trkB, BDNF, and NT-4 are not modulated by an excess of serotonin during barrel formation, (2) TrkB signaling limits branching of TCAs in inappropriate supragranular cortical layers, and (3) serotonin and TrkB signaling act together to cluster thalamocortical axons in layer IV.