Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-25T05:57:28.590Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Get access Rights & Permissions [Opens in a new window]

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Alsina, B., Vu, T., & Cohen-Cory, S. (2001). Visualizing synapse formation in arborizing optic axons in vivo: dynamics and modulation by BDNF. Nature Neuroscience 4, 1093–1101.Google Scholar
Ames, III, A. & Nesbett, F.B. (1981). In vitro retina as an experimental model of the central nervous system. Journal of Neurochemistry 37, 867–877.Google Scholar
Ball, S.L., Powers, P.A., Shin, H.S., Morgans, C.W., Peachey, N.S., & Gregg, R.G. (2002). Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer plexiform layer. Investigative Ophthalmology and Visual Science 43, 1595–1603.Google Scholar
Barnett, N.L. & Pow, D.V. (2000). Antisense knockdown of GLAST, a glial glutamate transporter, compromises retinal function. Investigative Ophthalmology and Visual Science 41, 585–591.Google Scholar
Bennett, J.L., Zeiler, S.R., & Jones, K.R. (1999). Patterned expression of BDNF and NT-3 in the retina and anterior segment of the developing mammalian eye. Investigative Ophthalmology and Visual Science 40, 2996–3005.Google Scholar
Betz, W.J. & Bewick, G.S. (1992). Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction. Science 255, 200–203.Google Scholar
Cellerino, A. & Kohler, K. (1997). Brain-derived neurotrophic factor/neurotrophin-4 receptor TrkB is localized on ganglion cells and dopaminergic amacrine cells in the vertebrate retina. Journal of Comparative Neurology 386, 149–160.Google Scholar
Cusato, K., Bosco, A., Linden, R., & Reese, B.E. (2002). Cell death in the inner nuclear layer of the retina is modulated by BDNF. Brain Research Brain Research Reviews 139, 325–330.Google Scholar
Dhingra, A., Jiang, M., Wang, T.L., Lyubarsky, A., Savchenko, A., Bar-Yehuda, T., Sterling, P., Birnbaumer, L., & Vardi, N. (2002). Light response of retinal ON bipolar cells requires a specific splice variant of Galpha(o). Journal of Neuroscience 22, 4878–4884.Google Scholar
Di Polo, A., Cheng, L., Bray, G.M., & Aguayo, A.J. (2000). Colocalization of TrkB and brain-derived neurotrophic factor proteins in green-red-sensitive cone outer segments. Investigative Ophthalmology and Visual Science 41, 4014–4021.Google Scholar
Euler, T., Schneider, H., & Wassle, H. (1996). Glutamate responses of bipolar cells in a slice preparation of the rat retina. Journal of Neuroscience 16, 2934–2944.Google Scholar
Gonzalez, M., Ruggiero, F.P., Chang, Q., Shi, Y.J., Rich, M.M., Kraner, S., & Balice-Gordon, R.J. (1999). Disruption of Trkb-mediated signaling induces disassembly of postsynaptic receptor clusters at neuromuscular junctions. Neuron 24, 567–583.Google Scholar
Green, D.G. & Kapousta-Bruneau, N.V. (1999). A dissection of the electroretinogram from the isolated rat retina with microelectrodes and drugs. Visual Neuroscience 16, 727–741.Google Scholar
Harada, T., Harada, C., Kohsaka, S., Wada, E., Yoshida, K., Ohno, S., Mamada, H., Tanaka, K., Parada, L.F., & Wada, K. (2002). Microglia-Muller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration. Journal of Neuroscience 22, 9228–9236.Google Scholar
Harada, T., Harada, C., Nakayama, N., Okuyama, S., Yoshida, K., Kohsaka, S., Matsuda, H., & Wada, K. (2000). Modification of glial-neuronal cell interactions prevents photoreceptor apoptosis during light-induced retinal degeneration. Neuron 26, 533–541.Google Scholar
Harada, T., Harada, C., Watanabe, M., Inoue, Y., Sakagawa, T., Nakayama, N., Sasaki, S., Okuyama, S., Watase, K., Wada, K., & Tanaka, K. (1998). Functions of the two glutamate transporters GLAST and GLT-1 in the retina. Proceedings of the National Academy of Sciences of the U.S.A. 95, 4663–4666.Google Scholar
Haverkamp, S., Grunert, U., & Wassle, H. (2000). The cone pedicle, a complex synapse in the retina. Neuron 27, 85–95.Google Scholar
Haverkamp, S. & Wassle, H. (2000). Immunocytochemical analysis of the mouse retina. Journal of Comparative Neurology 424, 1–23.Google Scholar
Hempstead, B.L. (2002). The many faces of p75NTR. Current Opinion in Neurobiology 12, 260–267.Google Scholar
Huang, E.J. & Reichardt, L.F. (2001). Neurotrophins: Roles in neuronal development and function. Annual Review of Biochemistry 24, 677–736.Google Scholar
Huang, E.J. & Reichardt, L.F. (2003). TRK receptors: Roles in neuronal signal transduction. Annual Review of Biochemistry 72, 609–642.Google Scholar
Huang, Z.J., Kirkwood, A., Pizzorusso, T., Porciatti, V., Morales, B., Bear, M.F., Maffei, L., & Tonegawa, S. (1999). BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex. Cell 98, 739–755.Google Scholar
Hughes, T.E. (1997). Are there ionotropic glutamate receptors on the rod bipolar cell of the mouse retina? Visual Neuroscience 14, 103–109.Google Scholar
Kaplan, D.R. & Miller, F.D. (2000). Neurotrophin signal transduction in the nervous system. Current Opinion in Neurobiology 10, 381–391.Google Scholar
Karwoski, C.J. & Xu, X. (1999). Current source-density analysis of light-evoked field potentials in rabbit retina. Visual Neuroscience 16, 369–377.Google Scholar
Kay, A.R., Alfonso, A., Alford, S., Cline, H.T., Holgado, A.M., Sakmann, B., Snitsarev, V.A., Stricker, T.P., Takahashi, M., & Wu, L.U. (1999). Imaging synaptic activity in intact brain and slices with FM1-43 in C. elegans, lamprey, and rat. Neuron 24, 809–817.Google Scholar
Kossel, A.H., Cambridge, S.B., Wagner, U., & Bonhoeffer, T. (2001). A caged Ab reveals an immediate/instructive effect of BDNF during hippocampal synaptic potentiation. Proceedings of the National Academy of Sciences of the U.S.A. 98, 14702–14707.Google Scholar
Kovalchuk, Y., Hanse, E., Kafitz, K.W., & Konnerth, A. (2002). Postsynaptic induction of BDNF-mediated long-term potentiation. Science 295, 1729–1734.Google Scholar
Kurenny, D.E., Moroz, L.L., Turner, R.W., Sharkey, K.A., & Barnes, S. (1994). Modulation of ion channels in rod photoreceptors by nitric oxide. Neuron 13, 315–324.Google Scholar
Lei, B. & Perlman, I. (1999). The contributions of voltage- and time-dependent potassium conductances to the electroretinogram in rabbits. Visual Neuroscience 16, 743–754.Google Scholar
Li, G., Regunathan, S., Barrow, C.J., Eshraghi, J., Cooper, R., & Reis, D.J. (1994). Agmatine: an endogenous clonidine-displacing substance in the brain. Science 263, 966–969.Google Scholar
Li, G., Regunathan, S., & Reis, D.J. (1995). Agmatine is synthesized by a mitochondrial arginine decarboxylase in rat brain. Annals of the New York Academy of Sciences 763, 325–329.Google Scholar
Llamosas, M.M., Cernuda-Cernuda, R., Huerta, J.J., Vega, J.A., & Garcia-Fernandez, J.M. (1997). Neurotrophin receptors expression in the developing mouse retina: An immunohistochemical study. Anatomy and Embryology 195, 337–344.Google Scholar
Lom, B., Cogen, J., Sanchez, A.L., Vu, T., & Cohen-Cory, S. (2002). Local and target-derived brain-derived neurotrophic factor exert opposing effects on the dendritic arborization of retinal ganglion cells in vivo. Journal of Neuroscience 22, 7639–7649.Google Scholar
Marc, R.E. (1999a). Kainate activation of horizontal, bipolar, amacrine, and ganglion cells in the rabbit retina. Journal of Comparative Neurology 407, 65–76.Google Scholar
Marc, R.E. (1999b). Mapping glutamatergic drive in the vertebrate retina with a channel- permeant organic cation. Journal of Comparative Neurology 407, 47–64.Google Scholar
Marc, R.E. & Jones, B.W. (2002). Molecular phenotyping of retinal ganglion cells. Journal of Neuroscience 22, 413–427.Google Scholar
Marc, R.E., Liu, W.L., Kalloniatis, M., Raiguel, S.F., & van Haesendonck, E. (1990). Patterns of glutamate immunoreactivity in the goldfish retina. Journal of Neuroscience 10, 4006–4034.Google Scholar
Masu, M., Iwakabe, H., Tagawa, Y., Miyoshi, T., Yamashita, M., Fukuda, Y., Sasaki, H., Hiroi, K., Nakamura, Y., Shigemoto, R., & et al. (1995). Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene. Cell 80, 757–765.Google Scholar
McGillem, G.S. & Dacheux, R.F. (2001). Rabbit cone bipolar cells: Correlation of their morphologies with whole-cell recordings. Visual Neuroscience 18, 675–685.Google Scholar
Meyer-Franke, A., Wilkinson, G.A., Kruttgen, A., Hu, M., Munro, E., Hanson, J.M.G., Reichardt, L.F., & Barres, B.A. (1998). Depolarization and cAMP elevation rapidly recruit TrkB to the plasma membrane of CNS neurons. Neuron 21, 681–693.Google Scholar
Micheva, K.D., Buchanan, J., Holz, R.W., & Smith, S.J. (2003). Retrograde regulation of synaptic vesicle endocytosis and recycling. Nature Neuroscience 6, 925–932.Google Scholar
Patapoutian, A. & Reichardt, L.F. (2001). Trk receptors: Mediators of neurotrophin action. Current Opinion in Neurobiology 11, 272–280.Google Scholar
Pollock, G.S. & Frost, D.O. (2003). Complexity in the modulation of neurotrophic factor mRNA expression by early visual experience. Brain Research Brain Research Reviews 143, 225–232.Google Scholar
Pugh, Jr., E.N., Falsini, B., & Lyubarsky, A.L. (1998). The origin of the major rod- and cone-driven components of the rodent electroretinogram and the effect of age and light-rearing history on the magnitude of these components. In Photostasis and Related Phenomena, ed. Williams, T.P. & Thistle, A.B. pp. 93–128. New York: Plenum Press.
Rauen, T., Rothstein, J.D., & Wassle, H. (1996). Differential expression of three glutamate transporter subtypes in the rat retina. Cell Tissue Research 286, 325–336.Google Scholar
Rickman, D.W. & Brecha, N.C. (1995). Expression of the proto-oncogene, trk, receptors in the developing rat retina. Visual Neuroscience 12, 215–222.Google Scholar
Rico, B., Xu, B., & Reichardt, L.F. (2002). TrkB receptor signaling is required for establishment of GABAergic synapses in the cerebellum. Nature Neuroscience 5, 225–233.Google Scholar
Robson, J.G. & Frishman, L.J. (1995). Response linearity and kinetics of the cat retina: The bipolar cell component of the dark-adapted electroretinogram. Visual Neuroscience 12, 837–850.Google Scholar
Rohrer, B., Korenbrot, J.I., La Vail, M.M., Reichardt, L.F., & Xu, B. (1999). Role of neurotrophin receptor TrkB in the maturation of rod photoreceptors and establishment of synaptic transmission to the inner retina. Journal of Neuroscience 19, 8919–8930.Google Scholar
Rohrer, B. & Ogilvie, J.M. (2003). Retarded outer segment development in TrkB knockout mouse retina organ culture. Molecular Vision 9, 18–23.Google Scholar
Slaughter, M.M. & Miller, R.F. (1985). Characterization of an extended glutamate receptor of the on bipolar neuron in the vertebrate retina. Journal of Neuroscience 5, 224–233.Google Scholar
Tsukamoto, Y., Morigiwa, K., Ueda, M., & Sterling, P. (2001). Microcircuits for night vision in mouse retina. Journal of Neuroscience 21, 8616–8623.Google Scholar
Ugolini, G., Cremisi, F., & Maffei, L. (1995). TrkA, TrkB and p75 mRNA expression is developmentally regulated in the rat retina. Brain Research 704, 121–124.Google Scholar
Vardi, N., Morigiwa, K., Wang, T.L., Shi, Y.J., & Sterling, P. (1998). Neurochemistry of the mammalian cone ‘synaptic complex’. Vision Research 38, 1359–1369.Google Scholar
Vecino, E., Garcia-Grespo, D., Garcia, M., Martinez-Millan, L., Sharma, S.C., & Carrascal, E. (2002). Rat retinal ganglion cells co-express brain derived neurotrophic factor (BDNF) and its receptor TrkB. Vision Research 42, 151–157.Google Scholar
Wahlin, K.J., Adler, R., Zack, D.J., & Campochiaro, P.A. (2001). Neurotrophic signaling in normal and degenerating rodent retinas. Experimental Eye Research 73, 693–701.Google Scholar
Yoshida, K., Imaki, J., Okamoto, Y., Iwakabe, H., Fujisawa, H., Matsuda, A., Nakanisi, S., Matsuda, H., & Hagiwara, M. (1998). CREB-induced transcriptional activation depends on mGluR6 in rod bipolar cells. Brain Research Molecular Brain Research 57, 241–247.Google Scholar
Zhang, X. & Poo, M.M. (2002). Localized synaptic potentiation by BDNF requires local protein synthesis in the developing axon. Neuron 36, 675–688.Google Scholar