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Functionally intact glutamate-mediated signaling in bipolar cells of the TRKB knockout mouse retina

Published online by Cambridge University Press:  01 September 2004

BAERBEL ROHRER ,
ROMAN BLANCO ,
ROBERT E. MARC ,
MARCIA B. LLOYD ,
DEAN BOK ,
DAVID M. SCHNEEWEIS  and
LOUIS F. REICHARDT
BAERBEL ROHRER
Affiliation:
Department of Ophthalmology, Medical University of South Carolina, Charlston Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston
ROMAN BLANCO
Affiliation:
Department of Ophthalmology, Universidad Autonoma of Barcelona, Barcelona, Spain
ROBERT E. MARC
Affiliation:
Department of Ophthalmology, University of Utah School of Medicine, Salt Lake City
MARCIA B. LLOYD
Affiliation:
Departments of Neurobiology, Jules Stein Eye Institute and Brain Research Institute, University of California Los Angeles, Los Angeles
DEAN BOK
Affiliation:
Departments of Neurobiology, Jules Stein Eye Institute and Brain Research Institute, University of California Los Angeles, Los Angeles
DAVID M. SCHNEEWEIS
Affiliation:
Department of BioEngineering, University of Illinois at Chicago, Chicago
LOUIS F. REICHARDT
Affiliation:
Howard Hughes Medical Institute, University of California San Francisco, San Francisco
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Abstract

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.

Keywords

Patch clamp recordingAgmatine uptakeElectronmicroscopySynapseExcitatory amino acid transporter
Type
Research Article
Information
Visual Neuroscience , Volume 21 , Issue 5 , September 2004 , pp. 703 - 713
Copyright
2004 Cambridge University Press

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