Research projects

Agenesis of the corpus callosum (ACC) covers a series of rare diseases characterised by the absence of the axonal tract, which connects the two hemispheres of the brain. Innovative advances have shown the high therapeutic potential arising from the plasticity of the nervous system. Our research reveals the importance of plasticity and intrinsic excitability during the creation of the CC. Cux1 transcription factor appears to be an early cause of this process, regulating the expression of Kv1 potassium channels and the response trigger. Loss of Cux1 in the callos neurons leads to the complete elimination of its contralateral axons during postnatal development. However, activation of plasticity mechanisms and certain ion channels are sufficient to restore these connections. This gives rise to an excellent model for dissecting the basic mechanisms by which the CC is formed in connection with plasticity, so that its potential use in the treatment of ACC may be evaluated. We will explore these mechanisms in vivo in mice, establishing innovative genetic manipulation techniques in the cerebral cortex. We will analyse the windows in time and the limitations imposed by the circuit on CC capacity to reconnect based on modulation of neuronal excitability, as well as the cortical circuits surrounding callosum neurons, using histological, electrophysiological and imaging techniques. The results will open up new pharmacological and genetic pathways for treatment and counterbalance ACC patients' symptoms. They will also be relevant for other diseases which affect the axon and cerebral connectivity.