Name: Pérez-Otaño, Isabel
Institution: Universidad de Navarra
Center: Centro de Investigación Médica Aplicada
Address: Avda. Pio XII, 55
31008 Pamplona. Spain
Phone: + 34 948 194700 x2009
Fax: + 34 948 194715
Glutamate receptors of the NMDA subtype (NMDARs) are critical regulators of brain development and plasticity, and alterations in their composition or abundance are implicated in diseases of the CNS such as Parkinson´s, Alzheimer´s, Huntington´s disease or schizophrenia. Structurally, NMDARs are tetrameric assemblies of an obligatory NR1 subunit and different combinations of four NR2 (A-D) or two NR3 (A-B) subunits. Classical NMDARs (NR1/NR2 heteromers) are highly permeable to calcium and mediate synaptic plasticity (LTP<D) but also the excitotoxic effects of glutamate. Heteromeric receptors including NR3A possess unique channel properties, can work as dominant-negative components of NMDAR complexes by inhibiting classical NMDAR activity, and their expression is strictly regulated to avoid potential pathological effects resulting from NMDAR hypofunction.
NMDARs with different subunit composition have different locations and functions, indeed neurons use a wide range of cell-biological processes to regulate their trafficking and thus determine the number/types of receptor channels that reach the plasma membrane and ultimately the synapse. We use a combination of molecular, biochemical, imaging and electrophysiological techniques in cell lines, primary neuronal cultures and brain slices to:
1) Address rules governing NMDAR local exo/endocytic trafficking, with a foucs on local trafficking and receptor sorting.
2) Define the impact of alterations in NMDAR trafficking in neurodegenerative disease.
3) Study developmental changes in NMDAR signaling and their roles in the elaboration and subsequent remodeling of neuronal networks in response to experience.