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Eradication of cerebellar granular cells alters thedevelopmental expression of TRK receptors in the ratinferior olive
Author(s) -
Rivadepaty Isabelle,
Dubreuil Yolande Lemaigre,
Mariani Jean,
Delhayebouchaud Nicole
Publication year - 1998
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/s0736-5748(98)00004-5
Subject(s) - cerebellum , inferior olivary nucleus , cerebellar cortex , granule cell , tropomyosin receptor kinase b , biology , neuroscience , purkinje cell , downregulation and upregulation , receptor , microbiology and biotechnology , chemistry , neurotrophic factors , central nervous system , biochemistry , dentate gyrus , gene
Granule cells which relay the mossy fibre afferent system to the cerebellar cortex aregenerated postnatally in mammals. In their absence, the climbing fibres, i.e. the second afferentsystem to the cerebellum originating in the inferior olivary nucleus, remain in an immature stage,and substantial elimination of redundant synapses they establish on the Purkinje cells does notoccur in the rat between day five (P5) and day fifteen (P15). It is generally assumed that synapseelimination is partly regulated by electrical activity which modulates the competition amongafferent fibres for the uptake of a limited amount of trophic factors released by the target. Theneurotrophins, whose expression is developmentally regulated in the cerebellum, especially ingranule cells, could be this retrograde signal. Using RT‐PCR, we studied the expression of theirtrk receptors in the inferior olivary nucleus of developing and adult rats, and its alteration aftereradication of the granule cell precursors by X‐irradiation on P5. From P0 to P90, the amount oftrkA mRNA is low and remains stable in control rats ; the high levels of trkB and C mRNAsdetected at P0 markedly decrease in parallel from P5 and reach their minimal values at P15,when the process of synapse elimination is completed in the cerebellum. X‐irradiation of thecerebellum decreases the level of expression of the three trks, but a transient upregulation of trkCoccurs at P10. The downregulation of trkB and C expression in the inferior olivary nucleus,contemporary with the altered expression of neurotrophins in the cerebellum, suggest that NT‐3and/or BDNF/NT‐4/5 could be involved in the remodelling of olivocerebellar relationshipsduring development. In addition, the transient overexpression of trkC after granule cellseradication is consistent with a paracrin effect exerted on the olivary cells by granule cells releaseof NT‐3, at the time when the climbing fibres invest the growing Purkinje cell dendrites in themolecular layer.