Visual Neuroscience



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


BAERBEL  ROHRER  a1 a2 c1 , ROMAN  BLANCO  a3 , ROBERT E.  MARC  a4 , MARCIA B.  LLOYD  a5 , DEAN  BOK  a5 , DAVID M.  SCHNEEWEIS  a6 and LOUIS F.  REICHARDT  a7
a1 Department of Ophthalmology, Medical University of South Carolina, Charlston
a2 Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston
a3 Department of Ophthalmology, Universidad Autonoma of Barcelona, Barcelona, Spain
a4 Department of Ophthalmology, University of Utah School of Medicine, Salt Lake City
a5 Departments of Neurobiology, Jules Stein Eye Institute and Brain Research Institute, University of California Los Angeles, Los Angeles
a6 Department of BioEngineering, University of Illinois at Chicago, Chicago
a7 Howard Hughes Medical Institute, University of California San Francisco, San Francisco

Article author query
rohrer b   [Google Scholar] 
blanco r   [Google Scholar] 
marc re   [Google Scholar] 
lloyd mb   [Google Scholar] 
bok d   [Google Scholar] 
schneeweis dm   [Google Scholar] 
reichardt lf   [Google Scholar] 
 

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.

(Received January 9 2004)
(Accepted June 8 2004)


Key Words: Patch clamp recording; Agmatine uptake; Electronmicroscopy; Synapse; Excitatory amino acid transporter.

Correspondence:
c1 Address correspondence and reprint requests to: Baerbel Rohrer, Department of Ophthalmology, Medical University of South Carolina, 167 Ashley Avenue, Charleston, SC, 29425, USA. E-mail: rohrer@musc.edu