Functionally intact glutamate-mediated signaling in bipolar cells of the TRKB knockout mouse retina.
In the juvenile trkB knockout (trkB-/-) mouse, retina synaptic communication from rods to bipolar cells is severely compromised as evidenced by a complete absence of electroretinogram (ERG) b-wave, even though the inner retina appears anatomically normal (Rohrer et al., 1999). Since it is well known that the b-wave reflects light-dependent synaptic activation of ON bipolar cells via their metabotropic glutamate receptor, mGluR6, we sought to analyze the anatomical and functional integrity of the glutamatergic synapses at these and other bipolar cells in the trkB(-/-) mouse. Although rod bipolar cells from wild-type juvenile mice were determined to be immunopositive for trkB, postsynaptic metabotropic and ionotropic glutamate receptor-mediated pathways in ON and OFF bipolar cells were found to be functionally intact, based on patch electrode recordings, using brief applications ("puffs") of glutamate or its analog, 2-amino-4-phosphonobutyric acid (APB), a selective agonist for mGluR6 receptors. Ionotropic glutamate receptor function was assayed in OFF-cone bipolar and horizontal cells by applying exogenous glutamatergic agonists in the presence of the channel-permeant guanidinium analogue, 1-amino-4-guanidobutane (AGB). Electron-microscopic analysis revealed that the ribbon synapses between rods and postsynaptic rod bipolar and horizontal cells were formed at the appropriate age and appear to be structurally intact, and immunohistochemical analysis did not detect profound defects in the expression of excitatory amino acid transporters involved in glutamate clearance from the synaptic cleft. These data indicate that there does not appear to be evidence for postsynaptic deficits in glutamatergic signaling in the ON and OFF bipolar cells of mice lacking trkB.
Rohrer
Baerbel
B
Department of Ophthalmology, Medical University of South Carolina, Charlston, SC 29425, USA. rohrer@musc.edu
Blanco
Roman
R
Marc
Robert E
RE
Lloyd
Marcia B
MB
Bok
Dean
D
Schneeweis
David M
DM
Reichardt
Louis F
LF
D000376:Agmatine / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D005260:Female; D017353:Gene Deletion; D018698:Glutamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D007395:Interneurons / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D020813:Receptor, trkB / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission; D014785:Vision, Ocular / Q000187:drug effects*
D000613:Aminobutyrates; D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6; D018698:Glutamic Acid; D000376:Agmatine; D020813:Receptor, trkB; C012729:2-amino-4-phosphonobutyric acid