Abstract
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.
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Acknowledgments
We wish to thank Elodie Bui-Dinh and Micol Maritan for technical assistance. The study was supported in part by the Institut de la Recherche sur la Moelle épinière et l’Encéphale et La Fondation de la Recherche Médicale.
Conflict of Interest
There are no current or potential conflicts of interest for the four authors: Drs. RM Sherrard, M Letellier, AM Lohof and J Mariani.
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Sherrard, R.M., Letellier, M., Lohof, A.M. et al. Formation and Reformation of Climbing Fibre Synapses in the Cerebellum: a Similar Story?. Cerebellum 12, 319–321 (2013). https://doi.org/10.1007/s12311-012-0443-x
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DOI: https://doi.org/10.1007/s12311-012-0443-x