Daniel Zamanillo, ^1* Rolf Sprengel, ¹ Øivind Hvalby, ² Vidar Jensen, ² Nail Burnashev, ¹ Andrei Rozov, ¹ Katharina M. M. Kaiser, ¹ Helmut J. Köster, ¹ Thilo Borchardt, ¹ Paul Worley, ³ Joachim Lübke, ⁴ Michael Frotscher, ⁴ Peter H. Kelly, ⁵ Bernd Sommer, ⁵ Per Andersen, ² Peter H. Seeburg, ¹ Bert Sakmann ¹

Gene-targeted mice lacking the L--amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit GluR-A exhibited normal development, life expectancy, and fine structure of neuronal dendrites and synapses. In hippocampal CA1 pyramidal neurons, GluR-A^/ mice showed a reduction in functional AMPA receptors, with the remaining receptors preferentially targeted to synapses. Thus, the CA1 soma-patch currents were strongly reduced, but glutamatergic synaptic currents were unaltered; and evoked dendritic and spinous Ca²⁺ transients, Ca²⁺-dependent gene activation, and hippocampal field potentials were as in the wild type. In adult GluR-A^/ mice, associative long-term potentiation (LTP) was absent in CA3 to CA1 synapses, but spatial learning in the water maze was not impaired. The results suggest that CA1 hippocampal LTP is controlled by the number or subunit composition of AMPA receptors and show a dichotomy between LTP in CA1 and acquisition of spatial memory.

¹ Departments of Molecular Neuroscience and Cell Physiology, Max-Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.
² Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Norway.
³ Departments of Neuroscience and Neurology, Johns Hopkins University, School of Medicine, Baltimore MD 21205, USA.
⁴ Department of Anatomy, University of Freiburg, Albertstrasse 17, D-79104 Freiburg, Germany.
⁵ NS Research Novartis Pharma AG, Basel, Switzerland.
^*   Present address: Laboratorios Doctor Esteve, Avenida Mare de Deu de Montserrat 221, 08041 Barcelona, Spain.

   To whom correspondence should be addressed. E-mail: sprengel{at}mpimf-heidelberg.mpg.de