Importance of AMPA Receptors for Hippocampal Synaptic Plasticity But Not for Spatial Learning

TLDR

In CA1 pyramidal neurons, GluR‑A knockout mice had fewer functional AMPA receptors, with the remaining ones concentrated at synapses. Mice lacking the GluR‑A subunit develop normally and preserve synaptic structure, yet exhibit reduced CA1 soma currents, abolished CA3‑to‑CA1 LTP, but normal glutamatergic synaptic currents, Ca²⁺ signaling, and spatial learning, showing that AMPA receptor number or composition controls CA1 LTP but not spatial memory acquisition.

Abstract

Gene-targeted mice lacking the L-alpha-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.