Glutamatergic axon-derived BDNF controls GABAergic synaptic differentiation in the cerebellum
| Autor: | Albert I. Chen, Eliezer Masliah, Louis F. Reichardt, Keling Zang |
|---|---|
| Přispěvatelé: | School of Biological Sciences, Warwick-NTU Neuroscience Programme |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cerebellum 1.1 Normal biological development and functioning Glutamic Acid Gene Expression Mice Transgenic Tropomyosin receptor kinase B Neurodegenerative Article Transgenic Mice 03 medical and health sciences Nerve Fibers 0302 clinical medicine Contactin 1 Underpinning research Golgi cell Receptors medicine Animals Mossy fiber (cerebellum) GABAergic Neurons Nerve Endings Brain-derived neurotrophic factor Multidisciplinary GABA-A Chemistry Brain-Derived Neurotrophic Factor Neurosciences Anatomy Receptors GABA-A Granule cell Axons Science::Biological sciences [DRNTU] Other Physical Sciences Protein Transport 030104 developmental biology medicine.anatomical_structure nervous system Cerebellar cortex Synapses Neurological GABAergic Biochemistry and Cell Biology Neuroscience 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Scientific reports, vol 6, iss 1 Scientific Reports Chen, AI; Zang, K; Masliah, E; & Reichardt, LF. (2016). Glutamatergic axon-derived BDNF controls GABAergic synaptic differentiation in the cerebellum. SCIENTIFIC REPORTS, 6. doi: 10.1038/srep20201. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/9wz5164j |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep20201 |
| Popis: | To study mechanisms that regulate the construction of inhibitory circuits, we examined the role of brain-derived neurotrophic factor (BDNF) in the assembly of GABAergic inhibitory synapses in the mouse cerebellar cortex. We show that within the cerebellum, BDNF-expressing cells are restricted to the internal granular layer (IGL), but that the BDNF protein is present within mossy fibers which originate from cells located outside of the cerebellum. In contrast to deletion of TrkB, the cognate receptor for BDNF, deletion of Bdnf from cerebellar cell bodies alone did not perturb the localization of pre- or postsynaptic constituents at the GABAergic synapses formed by Golgi cell axons on granule cell dendrites within the IGL. Instead, we found that BDNF derived from excitatory mossy fiber endings controls their differentiation. Our findings thus indicate that cerebellar BDNF is derived primarily from excitatory neurons—precerebellar nuclei/spinal cord neurons that give rise to mossy fibers—and promotes GABAergic synapse formation as a result of release from axons. Thus, within the cerebellum the preferential localization of BDNF to axons enhances the specificity through which BDNF promotes GABAergic synaptic differentiation. |
| Databáze: | OpenAIRE |
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