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Peter H. Seeburg
Max Planck Institute for Medical Research, Department of Molecular Neurobiology, Heidelberg, Germany
Peter Seeburg received his Diploma in Biochemistry in 1972 and his PhD in Genetics in 1975, both from the University of Tübingen. He was a postdoctoral fellow at the University of California, San Francisco, where he became an Adjunct Assistant Professor in Medicine in 1977. He joined Genentech, Inc. as Senior Scientist in 1978 and became Staff Scientist in 1985. He moved to the Center for Molecular Biology (ZMBH) of Heidelberg University as Full Professor in 1987 and became Director of the Department of Molecular Neurobiology at the Max Planck Institute for Medical Research in 1996. His scientific achievements include the engineering of E.coli for the production of human growth hormone, the characterization of GABA-A/benzodiazepine receptors and their molecular and functional diversity in the brain, as well as the molecular and functional delineation of brain ionotropic glutamate receptors and their subtypes. His current research focuses on the role of particular AMPA and NMDA receptor determinants in spatial learning in mice.
AMPA receptors and hippocampal functions
Peter H. Seeburg1, Rolf Sprengel1, David Bannerman2 and Hannah Monyer3
1Max Planck Institute for Medical Research, Heidelberg, Germany; 2Institute for Experimental Animal Psychology, Oxford University, UK; 3Dept. Clinical Neurobiology, Heidelberg University, Germany
AMPA receptors mediate the bulk of fast excitatory transmission in central synapses. These receptors are formed by assembly into tetrameric stoichiometry of mostly two of the four subunits, GluA1-GluA4. AMPA receptors in vivo contain auxiliary subunits, of which ‘stargazin’ and TARPs are prominent examples, which modulate the functional receptor properties. We have characterized a novel auxiliary AMPA receptor subunit, CKAMP44, a type I transmembrane protein featuring an extracellular putative cystine knot structure similar to such structures in neurotoxins. CKAMP44 is expressed at low levels in hippocampal CA1 pyramidal cells but at high levels in dentate gyrus granule cells. As a consequence, paired-pulse stimulation of perforant path-granule cell synapses generates depressing AMPA receptor-mediated excitatory postsynaptic currents (EPSCs), whereas the same stimulation at Schaffer collateral/commissural CA1 cell synapses leads to EPSC facilitation. Thus, CKAMP44 modulates by postsynaptic action short-term plasticity at selective excitatory synapses.
In the hippocampus, a brain structure essential for memory acquisition, the most prominent AMPA receptor is GluA1/A2. This AMPA receptor subtype is Ca2+ impermeable due to the presence of the Q/R site-edited GluA2 subunit. Genetic GluA1 ablation in the mouse leads to loss of long-term potentiation of the field EPSP in CA3-to-CA1 synapses, with no detrimental effect on the ability of the mice to acquire spatial reference memory, as tested on the Morris water maze or the Y-maze. GluA1 mutant mice display however a profound and lasting impairment on spatial short-term habituation, as tested on the T-maze. Intriguingly, the mutant mice perform better than their wild-type litter mates on associative long-term habituation, indicating interference of short-term habituation in the wild type.
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