Formation and reformation of climbing fibre synapses in the cerebellum: A similar story?

Rachel M. Sherrard, Mathieu Letellier, Ann M. Lohof, Jean Mariani
Cerebellum. 2013-01-17; 12(3): 319-321
DOI: 10.1007/s12311-012-0443-x

PubMed
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The assembly of neural circuits involves multiple sequential steps, in particular
the formation and maturation of synaptic connections. This often prolonged
process involves several stages including the appropriate morphological and
physiological maturation of each synaptic partner as well as their mutual
interaction in order to ensure correct cellular and subcellular targeting.
Understanding the processes involved becomes critical if neural circuits are to
be appropriately reassembled following lesion, atrophy or neurodegeneration. We
study the climbing fibre to Purkinje cell synapse as an example of a neural
circuit which undergoes initial synaptic formation, selective stabilisation and
elimination of redundant connections, in order to better understand the relative
roles of each synaptic partner in the process of synaptogenesis and post-lesion
synapse reformation. In particular, we are interested in the molecules which may
underlie these processes. Here, we present data showing that the maturational
state of both the target Purkinje cell and the climbing fibre axon influence
their capacity for synapse formation. The climbing fibre retains some ability to
recapitulate developmental processes irrespective of its maturational state. In
contrast, the experience of synaptic formation and selective
stabilisation/elimination permanently changes the Purkinje cell so that it cannot
be repeated. Thus, if the climbing fibre-Purkinje cell synapse is recreated after
the period of normal maturation, the process of synaptic competition, involving
the gradual weakening of one climbing fibre synapse and stabilisation of another,
no longer takes place. Moreover, we show that these processes of synaptic
competition can only proceed during a specific developmental phase. To understand
why these changes occur, we have investigated the role of molecules involved in
the development of the olivocerebellar path and show that brain-derived
neurotrophic factor, through activation of its receptor TrkB, as well as
polysialated neural cell adhesion molecule and the transcription factor RORα
regulate these processes.

 


Auteurs Bordeaux Neurocampus