Control of dopamine release in the retina: a transgenic approach to neural networks.
Dopaminergic, interplexiform amacrines (DA cells) were labeled in transgenic mice with human placental alkaline phosphatase, an enzyme that resides on the outer surface of the cell membrane. It was therefore possible to investigate their activity in vitro after dissociation of the retina with whole-cell current and voltage clamp, as well as their connections in the intact retina with the electron microscope. DA cells generate action potentials even in the absence of synaptic inputs. This activity is abolished by the amacrine cell transmitters GABA and glycine, which induce an inward current carried by chloride ions, and is stimulated by kainate, an agonist at the receptor for the bipolar cell transmitter glutamate, which opens nonselective cation channels. Since DA cells are postsynaptic to amacrine and bipolar cells, we suggest that the spontaneous discharge of DA cells is inhibited in the dark by GABAergic amacrines that receive their input from off-bipolars. Upon illumination, the GABA-inhibition is removed, DA cells generate action potentials, and their firing is modulated by the excitation received from on-bipolars.
Gustincich
S
S
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Feigenspan
A
A
Wu
D K
DK
Koopman
L J
LJ
Raviola
E
E
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002469:Cell Separation; D018076:DNA, Complementary; D004298:Dopamine / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D058851:GPI-Linked Proteins; D005998:Glycine / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007527:Isoenzymes / Q000032:analysis; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000502:physiology*; D008854:Microscopy, Electron; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D051381:Rats; D012160:Retina / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D013331:Strychnine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D015220:Calcium Channels; D018076:DNA, Complementary; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058851:GPI-Linked Proteins; D018684:Glycine Agents; D007527:Isoenzymes; D015221:Potassium Channels; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D014446:Tyrosine 3-Monooxygenase; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental; D013331:Strychnine; D007608:Kainic Acid; D005998:Glycine; D004298:Dopamine; D001640:Bicuculline