AMPA receptors (AMPARs) are the major mediators of fast excitatory neurotransmission in the retina as in other parts of the brain. In most neurons, the synaptic targeting, pharmacology, and function of AMPARs are influenced by auxiliary subunits including the transmembrane AMPA receptor regulatory proteins (TARPs). However, it is unclear which TARP subunits are present at retinal synapses and how they influence receptor localization and function.
View Article and Find Full Text PDFAdapting between scotopic and photopic illumination involves switching the routing of retinal signals between rod and cone-dominated circuits. In the daytime, cone signals pass through parallel On and Off cone bipolar cells (CBCs), that are sensitive to increments and decrements in luminance, respectively. At night, rod signals are routed into these cone-pathways via a key glycinergic interneuron, the AII amacrine cell (AII-AC).
View Article and Find Full Text PDFSilent voltage-gated potassium channel subunits (KS) interact selectively with members of the K2 channel family to modify their functional properties. The localization and functional roles of these silent subunits remain poorly understood. Mutations in the KS subunit, K8.
View Article and Find Full Text PDFPhotoreceptor degeneration differentially impacts glutamatergic signaling in downstream On and Off bipolar cells. In rodent models, photoreceptor degeneration leads to loss of glutamatergic signaling in On bipolar cells, whereas Off bipolar cells appear to retain glutamate sensitivity, even after extensive photoreceptor loss. The localization and identity of the receptors that mediate these residual glutamate responses in Off bipolar cells have not been determined.
View Article and Find Full Text PDFVisual signals are segregated into parallel pathways at the first synapse in the retina between cones and bipolar cells. Within the OFF pathways of mammals, the selective expression of AMPA or kainate-type glutamate receptors in the dendrites of different OFF-bipolar cell types is thought to contribute to formation of distinct temporal channels. AMPA receptors, with rapid recovery from desensitization, are proposed to transmit high temporal frequency signals, whereas kainate receptors (KARs) are presumed to encode lower temporal frequencies.
View Article and Find Full Text PDFIn the primate visual system, the ganglion cells of the magnocellular pathway underlie motion and flicker detection and are relatively transient, while the more sustained ganglion cells of the parvocellular pathway have comparatively lower temporal resolution, but encode higher spatial frequencies. Although it is presumed that functional differences in bipolar cells contribute to the tuning of the two pathways, the properties of the relevant bipolar cells have not yet been examined in detail. Here, by making patch-clamp recordings in acute slices of macaque retina, we show that the bipolar cells within the magnocellular pathway, but not the parvocellular pathway, exhibit voltage-gated sodium (NaV), T-type calcium (CaV), and hyperpolarization-activated, cyclic nucleotide-gated (HCN) currents, and can generate action potentials.
View Article and Find Full Text PDFDetailed analysis of the synaptic inputs to the primate DB1 bipolar cell has been precluded by the absence of a suitable immunohistochemical marker. Here we demonstrate that antibodies for the EF-hand calcium-binding protein, secretagogin, strongly label the DB1 bipolar cell as well as a mixed population of GABAergic amacrine cells in the macaque retina. Using secretagogin as a marker, we show that the DB1 bipolar makes synaptic contact with both L/M as well as S-cone photoreceptors and only minimal contact with rod photoreceptors.
View Article and Find Full Text PDFSecretagogin, a recently cloned member of the EF-hand family of calcium binding proteins, was localized in the mouse, rat, and rabbit retina using immunofluorescence immunohistochemistry. Secretagogin is expressed in subpopulations of ON and OFF cone bipolar cells; however, no immunoreactivity was observed in rod bipolar cells in any of these species. Using subtype-specific markers and mice expressing green fluorescent protein (GFP) within specific cell classes, we found that secretagogin is expressed in Types 2, 3, 4, 5, 6 and possibly Type 8 cone bipolar cells in the mouse retina.
View Article and Find Full Text PDFPhotoreceptor degenerations can trigger morphological alterations in second-order neurons, however, the functional implications of such changes are not well known. We conducted a longitudinal study, using whole-cell patch-clamp, immunohistochemistry and electron microscopy to correlate physiological with anatomical changes in bipolar cells of the rd10 mouse - a model of autosomal recessive retinitis pigmentosa. Rod bipolar cells (RBCs) showed progressive changes in mGluR6-induced currents with advancing rod photoreceptor degeneration.
View Article and Find Full Text PDFTo study the role of the metabotropic glutamate receptor 8 (mGluR8), mice lacking this receptor were generated by homologous recombination. Homozygous mGluR8-deficient mice are about 8% heavier than their wild-type age-matched controls after reaching 4 weeks of age. This weight difference is not caused by an altered food intake and is not exacerbated by feeding the animals a high-fat diet.
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