Evidence of calcium - permeable AMPA receptors 2 in dendritic spines of CA 1 pyramidal neurons

19 GluA2-lacking, calcium-permeable AMPA receptors have unique properties, but their presence 20 at excitatory synapses in pyramidal cells is controversial. We have tested certain predictions of 21 the model that such receptors are present in CA1 cells and show here that the polyamine 22 spermine, but not philanthotoxin, causes use-dependent inhibition of synaptically evoked 23 excitatory responses in str. radiatum, but not str. oriens in cultured and acute hippocampal 24 slices. Stimulation of single dendritic spines by photolytic release of caged glutamate induced 25 an NMDAR-independent, useand spermine-sensitive calcium influx only at apical spines in 26 cultured slices. Bath application of glutamate also triggered a spermine-sensitive influx of 27 cobalt into CA1 cell dendrites in str. radiatum. Responses of single apical, but not basal, spines 28 to photostimulation displayed prominent paired-pulse facilitation (PPF) consistent with use29 dependent relief of cytoplasmic polyamine block. Responses at apical dendrites were 30 diminished, and PPF was increased, by spermine. Intracellular application of pep2m, which 31 inhibits recycling of GluA2-containing AMPARs, reduced apical spine responses and increased 32 PPF. We conclude that some calcium-permeable, polyamine-sensitive AMPARs, perhaps lacking 33 GluA2 subunits, are present at synapses on apical dendrites of CA1 pyramidal cells, which may 34 allow distinct forms of synaptic plasticity and computation at different sets of excitatory inputs. 35