Functional modifications in rod bipolar cells in a mouse model of retinitis pigmentosa

The rd mouse has been widely used as an animal model of retinitis pigmentosa. In this model, a mutation of rod-specific phosphodiesterase leads to a loss of rods during the early period of postnatal life. Morphological modifications at the level of the outer plexiform layer have been shown (Proc. Nat. Acad. Sci. USA 97 (2000) 11020) in bipolar and horizontal cells. However, very little is known about the functional changes suffered by these cells postsynaptic to the degenerated rods. In the present work we have studied the neurotransmitter-induced currents in rod bipolar cells from the rd mouse retina. Currents induced by glutamate and GABA were studied by the patch clamp-whole cell technique, on rod bipolar cells enzymatically dissociated from the rd mouse retina. Data from rd animals were compared with non-dystrophic NMRI mice. GABA (30-100 micro M) and glutamate (100 micro M) were applied from a puff pipette in the near proximity of rod bipolar cell dendrites, clamped at physiological membrane potentials, and their evoked currents were studied. In rod bipolar cells from non-dystrophic mouse, puff application of glutamate induced an outward current. This current was increased twofold in absence of extracellular calcium (nominally 0 calcium). In rod bipolar cells from adult rd mouse, currents induced by glutamate were absent. Two types of GABA mediated currents were isolated in rod bipolar cells both in control and rd mouse retinas. The currents mediated by GABA(C) receptors were observed exclusively at the axon terminal, while the currents mediated by the GABA(A) receptors were observed upon GABA application to the bipolar cell dendrites. The currents mediated by GABA(A) receptors in rod bipolar cells from rd mouse were larger than those from control animals. We conclude that after the degeneration of rod photoreceptors in rd mouse, rod bipolar cells lost their glutamate (rod-neurotransmitter) input while they increase their response to GABA (horizontal cell-neurotransmitter). In our opinion, this work describes for the first time the changes in neurotransmitter sensitivity that affect rod bipolar cells after photoreceptor degeneration of the mouse retina.

[1]  P. Lukasiewicz,et al.  A diversity of GABA receptors in the retina. , 1998, Seminars in cell & developmental biology.

[2]  M. T. Davisson,et al.  Retinal degeneration mutants in the mouse , 2002, Vision Research.

[3]  S. Nawy.  Regulation of the On Bipolar Cell mGluR6 Pathway by Ca2+ , 2000, The Journal of Neuroscience.

[4]  M. Kalloniatis,et al.  Neurochemical architecture of the normal and degenerating rat retina , 1996, The Journal of comparative neurology.

[5]  M. Kalloniatis,et al.  Localisation of amino acid neurotransmitters during postnatal development of the rat retina , 1997, The Journal of comparative neurology.

[6]  P. Lukasiewicz,et al.  Different combinations of GABAA and GABAC receptors confer distinct temporal properties to retinal synaptic responses. , 1998, Journal of neurophysiology.

[7]  Y. Hao,et al.  Light-induced Changes of PKC Alpha Immunoreactivity in Rod Bipolar Cells of Normal and RD Mice , 2002 .

[8]  A. Kaneko,et al.  L-glutamate-induced responses and cGMP-activated channels in three subtypes of retinal bipolar cells dissociated from the cat , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[9]  T. Léveillard,et al.  Glial cell line-derived neurotrophic factor induces histologic and functional protection of rod photoreceptors in the rd/rd mouse. , 1999, Investigative ophthalmology & visual science.

[10]  C. F. Vaquero,et al.  Localisation of the GABAC receptors at the axon terminal of the rod bipolar cells of the mouse retina , 1999, Neuroscience Research.

[11]  Scott Nawy,et al.  Suppression by glutamate of cGMP-activated conductance in retinal bipolar cells , 1990, Nature.

[12]  Vision Research , 1961, Nature.

[13]  N. Vardi.  Alpha subunit of Go localizes in the dendritic tips of ON bipolar cells , 1998, The Journal of comparative neurology.

[14]  Tomomitsu Miyoshi,et al.  Specific deficit of the ON response in visual transmission by targeted disruption of the mGIuR6 gene , 1995, Cell.

[15]  E. Strettoi,et al.  Modifications of retinal neurons in a mouse model of retinitis pigmentosa. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[16]  H. Wässle,et al.  Different contributions of GABAA and GABAC receptors to rod and cone bipolar cells in a rat retinal slice preparation. , 1998, Journal of neurophysiology.

[17]  A. Kaneko,et al.  Transient calcium current of retinal bipolar cells of the mouse. , 1989, Neuroscience research. Supplement : the official journal of the Japan Neuroscience Society.

[18]  B. Sakmann,et al.  Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches , 1981, Pflügers Archiv.

[19]  J. Nathans,et al.  Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Vittorio Porciatti,et al.  Morphological and Functional Abnormalities in the Inner Retina of the rd/rd Mouse , 2002, The Journal of Neuroscience.

[21]  Ursula Greferath,et al.  Rod bipolar cells in the mammalian retina show protein kinase C‐like immunoreactivity , 1990, The Journal of comparative neurology.

[22]  A. Kaneko,et al.  Two types of calcium currents of the mouse bipolar cells recorded in the retinal slice preparation , 1998, The European journal of neuroscience.