Development of axon-target specificity of ponto-cerebellar afferents.

Abstract:

:The function of neuronal networks relies on selective assembly of synaptic connections during development. We examined how synaptic specificity emerges in the pontocerebellar projection. Analysis of axon-target interactions with correlated light-electron microscopy revealed that developing pontine mossy fibers elaborate extensive cell-cell contacts and synaptic connections with Purkinje cells, an inappropriate target. Subsequently, mossy fiber-Purkinje cell connections are eliminated resulting in granule cell-specific mossy fiber connectivity as observed in mature cerebellar circuits. Formation of mossy fiber-Purkinje cell contacts is negatively regulated by Purkinje cell-derived BMP4. BMP4 limits mossy fiber growth in vitro and Purkinje cell-specific ablation of BMP4 in mice results in exuberant mossy fiber-Purkinje cell interactions. These findings demonstrate that synaptic specificity in the pontocerebellar projection is achieved through a stepwise mechanism that entails transient innervation of Purkinje cells, followed by synapse elimination. Moreover, this work establishes BMP4 as a retrograde signal that regulates the axon-target interactions during development.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Kalinovsky A,Boukhtouche F,Blazeski R,Bornmann C,Suzuki N,Mason CA,Scheiffele P

doi

10.1371/journal.pbio.1001013

subject

Has Abstract

pub_date

2011-02-08 00:00:00

pages

e1001013

issue

2

eissn

1544-9173

issn

1545-7885

journal_volume

9

pub_type

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