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The Journal of Neuroscience, March 10, 2004, 24(10):2394-2400; doi:10.1523/JNEUROSCI.4040-03.2004

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Development/Plasticity/Repair
Altered Synapse Formation in the Adult Somatosensory Cortex of Brain-Derived Neurotrophic Factor Heterozygote Mice

Christel Genoud,¹ Graham W. Knott,¹ Kazuko Sakata,² Bai Lu,² and Egbert Welker¹

¹Institut de Biologie Cellulaire et de Morphologie, 1005 Lausanne, Switzerland, and ²Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-4480

Increased sensory stimulation in the adult whisker-to-barrel pathway induces the expression of BDNF as well as synapse formation in cortical layer IV. Here, we investigated whether BDNF plays a role in the alterations of connectivity between neurons by analyzing the ultrastructure of the BDNF heterozygote mouse, characterized by a reduced level of BDNF expression. Using serial section electron microscopy, we measured synapse density, spine morphology, and synaptic vesicle distribution to show that mice with a reduced level of BDNF have a barrel neuropil that is indistinguishable from wild-type controls. After 24 hr of whisker stimulation, however, there is no indication of synapse formation in the heterozygous mouse. Whereas the balance between excitatory and inhibitory synapses is modified in the controls, it remains constant in the heterozygotes. The distribution of synaptic vesicles in excitatory synapses is the same in heterozygous and wild-type mice and is not influenced by the stimulation paradigm. Spine volume, however, is unchanged by stimulation in the wild-type animals, but does increase significantly in the heterozygous animal. These results provide evidence that, in vivo, BDNF plays an important role in the structural rearrangement of adult cortical circuitry as a consequence of an increased sensory input.

Key words: BDNF; barrel; plasticity; synapse; GABA; spine; ultrastructure

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Received Sep 2, 2003; revised January 12, 2004; accepted January 12, 2004.

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