Régulation moléculaire de la synaptogenèse chez la souris / Mice, molecules and synapse formation
Texte intégral
Recherche
Responsable : Fekrije Selimi
Page web : https://www.college-de-france.fr/molecular-identity-and-diversity-of-synapses-in-the-brain.
1The mature brain is composed of morphologically and functionally distinct neuronal populations that form specific connections. This connectivity relies on the recognition of the target and of a precise subcellular domain for synapse formation. This phase is followed by refinement of the network through synapse stabilization or elimination. Furthermore, specific plasticity mechanisms enable the adaptation of the synapses to a changing environment through strengthening and weakening. Hence, each type of neuron integrates information received through several types of synapses that are characterized by a specific identity in terms of morphology, territory and function. The mammalian brain contains a huge diversity of synapses, the extent of which is only beginning to be deciphered. Our team’s goal is to decipher the molecular basis of synapse identity and its modulation by environmental factors during development.
2Molecular and activity-dependent mechanisms have been both proposed to determine the specificity of neuronal networks. Many results support the existence of a “chemoaffinity code”: each type of neuron expresses a specific combination of proteins that regulates its connectivity, leading to a specific molecular identity for each synapse type. Indeed, various categories of proteins have been implicated in the development of neuronal networks: adhesion molecules, guidance molecules, or even complement-related proteins. Some of these molecules also participate in synapse stabilization and maintenance in the adult nervous system. Activity, whether sensory-evoked or spontaneous, regulates neuronal network maturation, as shown in particular by studies of the neuromuscular junction, the visual system and the olivocerebellar network. However, the question of the relative contribution of “chemoaffinity” and activity-dependent regulation to the formation of specific synapses remains poorly understood. This question has implication for our understanding of brain development and of the etiologies of synaptopathies such as autism spectrum disorders or schizophrenia.
3We thus postulate that activity-dependent neuron-specific mechanisms control the molecular identity of synapses and the specific connectivity of each neuronal population. In the past few years, we have built an ambitious research program to demonstrate our hypothesis. Understanding this relationship will provide an integrated view of the construction of the mature brain. It will also highlight mechanisms that, if defective, could contribute to the etiology of synaptopathies.
4First, we have discovered the role of new immune-related proteins in neurons: C1q related proteins in input-specific connectivity (Sigoillot et al., Cell reports, 2015); IGSF3 as a new regulator of neuronal development (Usardi et al., Developmental Neurobiology, 2017); SUSD4 as a regulator of glutamate receptor numbers during synapse plasticity (González-Calvo, Iyer et al., eLife, 2021). Interestingly, comparison of these results with work in Caenorhabditis elegans shows that 1) conserved molecular domains control receptor clustering and synapse specification; 2) the addition of molecular modules during evolution, such as the C1q globular domain, contribute to the higher diversity of synapses in mammals (Cizeron, González-Calvo et al., submitted). Second, we have tackled a major technical challenge and established the tools to address the question of synapse molecular identity at the synapse-specific level in our model system, the mouse olivocerebellar network. Thanks to this effort, we are now finishing the first characterization of the presynaptic molecular combination underlying input-specific connectivity in a single type of neuron, the cerebellar Purkinje cell (Paul and Sigoillot et al., in preparation). Third, we are testing the effect of changes in neuronal activity during development on the molecular identity of synapses and neuronal connectivity using a pharmacological model of schizophrenia, the neonatal subchronic phencyclidine model (Veleanu et Urrieta-Chavez et al., in preparation).
Publications
5Cizeron M., González-Calvo I., Bessereau J.L. et Selimi F., « Synapse formation and function across species: ancient roles for CCP, CUB and TSR1 protein domains », sous presse.
González-Calvo I., Iyer K., Carquin M., Khayachi A., Giuliani F.A., Sigoillot S.M., Vincent J., Séveno M., Veleanu M., Tahraoui S., Albert M., Vigy O., Nadjar A., Dumoulin A., Triller A., Bessereau J.L., Rondi-Reig L., Isope P. et Selimi F., « Sushi domain-containing protein 4 controls synaptic plasticity and motor learning », eLife, vol. 10, 2021, art. e65712, https://doi.org/10.7554/eLife.65712.
Selimi F., « Déchiffrer le code moléculaire des synapses », La Recherche, numéro « Le cerveau », no 34, juin-août 2020.
Pour citer cet article
Référence papier
Fekrije Selimi, « Régulation moléculaire de la synaptogenèse chez la souris / Mice, molecules and synapse formation », L’annuaire du Collège de France, 121 | 2024, 697-699.
Référence électronique
Fekrije Selimi, « Régulation moléculaire de la synaptogenèse chez la souris / Mice, molecules and synapse formation », L’annuaire du Collège de France [En ligne], 121 | 2024, mis en ligne le 01 octobre 2024, consulté le 22 janvier 2026. URL : http://journals.openedition.org/annuaire-cdf/20115 ; DOI : https://doi.org/10.4000/12kvt
Haut de pageDroits d’auteur
Le texte et les autres éléments (illustrations, fichiers annexes importés), sont « Tous droits réservés », sauf mention contraire.
Haut de page
