Synapse-specific regulation of AMPA receptor subunit composition by activity.
We examined the changes that arise when neurotransmitter release is inhibited in a subpopulation of hippocampal neurons in coculture with normally active neighbors. Subsets of neurons were presynaptically silenced by chronic expression of tetanus toxin light chain tagged with cyan fluorescent protein (TNTCFP). Surprisingly, silenced neurons formed as many presynaptic terminals as their active neighbors when grown together on glial microislands. However, silenced neurons could not recruit the AMPA-type glutamate receptor subunit GluR1 as efficiently when competing with active neighbors. The immunofluorescence intensity ratio of GluR1 at synaptic puncta versus shaft was reduced by 22% opposite TNTCFP-expressing terminals compared with active neighbors. In contrast, this effect is abolished when vesicular release is blocked in all neurons. Local presynaptic inhibition by TNTCFP did not change the synaptic level of the AMPA receptor subunits GluR2 or GluR2/3 or of the PSD95 (postsynaptic density 95) family scaffolding proteins. Thus, neurotransmitter release selectively regulates the AMPA receptor population on a synapse-by-synapse basis but is not essential for an axon to efficiently compete for synaptic territory in a simple model system. These results demonstrate precise input specificity of postsynaptic receptor composition via differential activity among neighbor synapses.
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Kimberly J
KJ
Harms
Kenneth R
KR
Tovar
Ann Marie
AM
Craig
D000200:Action Potentials; D000818:Animals; D001253:Astrocytes; D001369:Axons / Q000378:metabolism; D002478:Cells, Cultured / Q000378:metabolism; D018920:Coculture Techniques; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018408:Patch-Clamp Techniques; D021122:Protein Subunits; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D013569:Synapses / Q000378:metabolism*; D014162:Transfection; D050988:Vesicle-Associated Membrane Protein 2 / Q000032:analysis
D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D021122:Protein Subunits; D018091:Receptors, AMPA; D017661:Receptors, Presynaptic; D011993:Recombinant Fusion Proteins; D050988:Vesicle-Associated Membrane Protein 2; C501449:Dlg4 protein, rat; C508140:SYNYFP protein; C508139:TNTCFP protein; C494706:Vamp2 protein, rat; C104723:glutamate receptor ionotropic, AMPA 3; C104722:glutamate receptor ionotropic, AMPA 2