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The Journal of Neuroscience, July 30, 2003, 23(17):6856-6865
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Brain-Derived Neurotrophic Factor Is Required for the Maintenance of Cortical Dendrites
Jessica A. Gorski, Steven R. Zeiler, Susan Tamowski, andKevin R. Jones Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309
Brain-derived neurotrophic factor (BDNF) is thought to be involved in neuronal survival, migration, morphological and biochemical differentiation, and modulation of synaptic function in the CNS. In the rodent cortex, postnatal BDNF expression is initially low but subsequently increases to reach maximal levels around weaning. Thus, BDNF expression peaks at a time when both structural and functional maturation of cortical circuitry occurs. Although the function of BDNF has been probed using many approaches, its requirements during this phase of life have not previously been examined genetically. To test the in vivo requirements for BDNF during this important phase of development we generated early-onset forebrain-specific BDNF mutant mice. Although these mice undergo forebrain-restricted deletion of BDNF by Cre-mediated recombination during embryogenesis, they are healthy, and we did not detect the loss of specific cortical excitatory or inhibitory neurons. However, the neocortex of 5-week-old mice was thinner, attributable at least partly to neuronal shrinkage. Importantly, although visual cortical layer 2/3 neurons in the mutants initially developed normal dendrite structure, dendritic retraction became apparent by 3 weeks of age. Thus, our observations suggest that cortically expressed BDNF functions to support the maintenance of cortical neuron size and dendrite structure rather than the initial development of these features. This is consistent with a role for BDNF in stabilizing the "survival" of circuitry during the phase of activity-dependent reorganization of cortical connectivity.
Key words: BDNF; dendrite; cortex; morphology; Cre-lox; neurotrophin; mouse; mutant
Received Mar. 25, 2003; revised Jun. 3, 2003; accepted Jun. 6, 2003.
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