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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/186815
Synaptic transmission in autaptic circuits: presynaptic homeostatic plasticity and microtubule dynamics
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[eng] Synapses are the contact sites where the transfer of information from the presynaptic to the postsynaptic site occurs. Correct processing of information requires that synapses continuously adapt their properties to an ever-changing environment. Here, we describe novel aspects that help understand the function of presynaptic terminals in the context of a simple neuronal network. The exuberant number of synaptic contacts formed during the development of the nervous system is selectively refined by a process of synapse elimination. In the current thesis we have exploited the action of peptide p4.2, a 20 amino acid fragment located in the C-terminus of the glial secreted protein SPARC, which promotes synapse elimination in an autaptic circuit. We found that neurons forming autaptic synapses sense and compensate for synapse elimination by activating a mechanism of presynaptic homeostatic plasticity driven by presynaptic potentiation and rapid assembly of new synaptic contacts. Both actions occur concomitantly, indicating that the formation of novel synapses is associated to an overall increase in presynaptic calcium influx. To further investigate the molecular mechanisms underlying this compensatory response, we moved our interests to the participation of microtubules in the maintenance of synaptic connectivity and synaptic strength. This question could only be addressed by gaining a better understanding of the participation of microtubules in presynaptic terminal function. By providing ultrastructural, morphological, and physiological evidence we have shown that microtubule plus-ends transiently invade presynaptic boutons and that microtubule instability is directly involved in the regulation of spontaneous neurotransmitter release probability. Microtubule polymerization is also important to postsynaptic function, indicating microtubule dynamics might be involved in forms of postsynaptic plasticity. Altogether, the development of this project has allowed to identify yet unknown mechanisms key for better understanding the cell biology of presynaptic terminals. These findings should not only be considered in the context of a simple neuronal network, chosen because of its unique experimental possibilities, but as fundamental neuronal properties. Yet, future research in complex systems are required to further validate our findings.
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VELASCO DOMÍNGUEZ, Cecilia. Synaptic transmission in autaptic circuits: presynaptic homeostatic plasticity and microtubule dynamics. [consulta: 8 de desembre de 2025]. [Disponible a: https://hdl.handle.net/2445/186815]