Evidence of calcium-permeable AMPA receptors in dendritic spines of CA1 pyramidal neurons.
GluA2-lacking, calcium-permeable α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPARs) have unique properties, but their presence at excitatory synapses in pyramidal cells is controversial. We have tested certain predictions of the model that such receptors are present in CA1 cells and show here that the polyamine spermine, but not philanthotoxin, causes use-dependent inhibition of synaptically evoked excitatory responses in stratum radiatum, but not s. oriens, in cultured and acute hippocampal slices. Stimulation of single dendritic spines by photolytic release of caged glutamate induced an N-methyl-d-aspartate receptor-independent, use- and spermine-sensitive calcium influx only at apical spines in cultured slices. Bath application of glutamate also triggered a spermine-sensitive influx of cobalt into CA1 cell dendrites in s. radiatum. Responses of single apical, but not basal, spines to photostimulation displayed prominent paired-pulse facilitation (PPF) consistent with use-dependent relief of cytoplasmic polyamine block. Responses at apical dendrites were diminished, and PPF was increased, by spermine. Intracellular application of pep2m, which inhibits recycling of GluA2-containing AMPARs, reduced apical spine responses and increased PPF. We conclude that some calcium-permeable, polyamine-sensitive AMPARs, perhaps lacking GluA2 subunits, are present at synapses on apical dendrites of CA1 pyramidal cells, which may allow distinct forms of synaptic plasticity and computation at different sets of excitatory inputs.
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland; Membrane Biology Training Program, University of Maryland School of Medicine, Baltimore, Maryland;
Hayley A
HA
Mattison
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland;
Ashish A
AA
Bagal
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland;
Michael
M
Mohammadi
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland; and.
Nisha S
NS
Pulimood
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland;
Christian G
CG
Reich
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland; Membrane Biology Training Program, University of Maryland School of Medicine, Baltimore, Maryland;
Bradley E
BE
Alger
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland; Membrane Biology Training Program, University of Maryland School of Medicine, Baltimore, Maryland; Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, Maryland.
Joseph P Y
JP
Kao
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland; Membrane Biology Training Program, University of Maryland School of Medicine, Baltimore, Maryland; sthom003@umaryland.edu.
Scott M
SM
Thompson
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D003035:Cobalt / Q000494:pharmacology; D049229:Dendritic Spines / Q000378:metabolism* / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D011073:Polyamines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D013096:Spermine / Q000494:pharmacology; D013569:Synapses / Q000378:metabolism / Q000502:physiology
D011073:Polyamines; D018091:Receptors, AMPA; D013096:Spermine; D003035:Cobalt; D018698:Glutamic Acid; C034092:delta-philanthotoxin; D002118:Calcium
calcium; glutamate; hippocampus; polyamines; synaptic transmission