Development, Homeostasis and Plasticity of Neural Circuits

Our objective is to understand the fundamental mechanisms that control the formation, maintenance and plasticity of synapses, microscopic structures that connect up neurons to form neural circuits. Our work focuses on the role of receptors for the neurotransmitter glutamate, the principal components of the signaling mechanism in excitatory synapses. Synaptic dysfunction is one of the first events in neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's, and in mental diseases such as schizophrenia, which means that the knowledge generated in these studies will provide tools to decipher the cellular and molecular bases of these disorders.

In the past 10 years, we have defined the biological functions of a subclass of NMDA glutamate receptors that contain the GluN3A subunit. GluN3A is typically expressed during the critical period of postnatal development and controls the balance between the processes of synapse maturation or elimination. Later, levels of GluN3A fall as result of activation of endocytosis processes modulated by neuron activity. Some diseases involve abnormal reactivation of the expression of GluN3A in the adult brain, which in states a juvenile state of plasticity or elimination of synapses and underlies the symptoms of Huntington's disease (HD) and cocaine addiction.

Projects in progress include the following:

  1. Study of the mechanisms that control synaptic maturation and elimination: The goal is to define the signaling pathways and molecular determinants of the physiological elimination of synapses during critical periods of development in the adult brain or neurodegenerative diseases such as Huntington's disease.

  2.  Regulation, glutamatergic receptors: Due to the key role of GluN3A in the consolidation of neural circuits and memory storage, we continue to be interested in the mechanisms that modulate its functional expression at the level of individual synapses and its dependence on activity

  3. Alterations in synaptic wiring in diseases of the central nervous system: A recent study by our group shows adult reactivation of the expression of GluN3A is a triggering factor in Huntington's disease, and we are currently exploring possible links with alcoholism and other forms of addiction. We are also developing pharmacological and genetic therapies to block the function or expression of Glu3Na and restore normal function.



"We have discovered a cell mechanism that causes the destruction of nerve connections, the blocking of which slows down degeneration in animal models of Huntington's disease", Dra. Isabel Pérez-Otaño.

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Contact

Contact:
Cristina Canciani
Avda. Pío XII, 53
31008 Pamplona
Spain

(+34) 948 194 700 Ext. 2013
canciani@unav.es