Funktionelle Charakterisierung neuer geklonter NMDA-Rezeptor-Untereinheiten - Implikationen für physiologische und pathophysiologische Mechanismen des Lernens im Tiermodell

• Applicant: Thomas Götz, Ph.D.
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2001 to 2004
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5340130

Fast excitatory neurotransmission in the CNS is mainly mediated by ionotropic glutamate receptors. A subset of these receptors, the NMDA-type receptors (NMDAR), play a pivotal role in synaptic plasticity and are implicated as pathogenic factors in a variety of acute and chronic neurodegenerative diseases. A thorough understanding of their functional properties extending from the molecular level to behavioural studies will help to explain and finally manipulate the physiology and pathophysiology of glutamatergic neurotransmission and thus brain function. Most recently two modulatory NMDAR subunits have been cloned (termed NR3A and NR3B). Their impact on the functional properties of NMDAR in a site- and timespecific manner has not been characterised yet. First investigations of the NR3Asubunit demonstrated attenuating effects on NMDAR mediated currents which indicates a putative neuroprotective function given the theory that overstimulation of NMDARs may lead to excitotoxic death. The proposed study seeks to elucidate and manipulate the functional properties of these regulatory subunits in rodents. Three models are currently available or near completion. NR3A knock-out mice [NR3A-/-] (Das et al., 1998) and NR3A transgenic mice [NR3Atg] are available. NR3B knock-out mice are under construction [NR3B-/-](SA Lipton, personal communication). We will use these mice to study the role of regulatory NMDAR subunits in synaptic plasticity phenomena by using a combination of the in vitro patch clamp technique, molecular biology and in vivo neurobehavioral tests.

• DFG Programme: Research Fellowships
• International Connection: USA
• Cooperation Partner: Professor Dr. Stuart A. Lipton