Synaptic and extrasynaptic factors governing glutamatergic retinal waves.
In the few days prior to eye-opening in mice, the excitatory drive underlying waves switches from cholinergic to glutamatergic. Here, we describe the unique synaptic and spatiotemporal properties of waves generated by the retina's glutamatergic circuits. First, knockout mice lacking vesicular glutamate transporter type 1 do not have glutamatergic waves, but continue to exhibit cholinergic waves, demonstrating that the two wave-generating circuits are linked. Second, simultaneous outside-out patch and whole-cell recordings reveal that retinal waves are accompanied by transient increases in extrasynaptic glutamate, directly demonstrating the existence of glutamate spillover during waves. Third, the initiation rate and propagation speed of retinal waves, as assayed by calcium imaging, are sensitive to pharmacological manipulations of spillover and inhibition, demonstrating a role for both signaling pathways in shaping the spatiotemporal properties of glutamatergic retinal waves.
Blankenship
Aaron G
AG
Neurosciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.
Ford
Kevin J
KJ
Johnson
Juliette
J
Seal
Rebecca P
RP
Edwards
Robert H
RH
Copenhagen
David R
DR
Feller
Marla B
MB
D026922:Amino Acid Transport Systems, Acidic / Q000172:deficiency; D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D016202:N-Methylaspartate / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D011724:Pyridazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D050598:Vesicular Glutamate Transport Protein 1 / Q000172:deficiency / Q000235:genetics
D026922:Amino Acid Transport Systems, Acidic; D001224:Aspartic Acid; D002118:Calcium; D004079:Dihydro-beta-Erythroidine; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018733:Nicotinic Antagonists; D011724:Pyridazines; D011810:Quinoxalines; D014633:Valine; D050598:Vesicular Glutamate Transport Protein 1; C493465:Slc17a7 protein, mouse; C120673:benzyloxyaspartate; C504941:Slc17a8 protein, mouse; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; C049853:gabazine