Analysis of Feedback Signaling from Horizontal Cells to Photoreceptors in Mice. 2018

Arlene A Hirano, and Xue Liu, and Nicholas C Brecha, and Steven Barnes
Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. ahirano@mednet.ucla.edu.

Genetic manipulation of horizontal cells using a Connexin57-iCre mouse (Cx57-iCre) line combined with calcium imaging is proving to be a valuable method to study horizontal cell feedback inhibition onto photoreceptor terminals. While it is accepted that horizontal cells provide lateral inhibitory feedback to photoreceptors, the cellular mechanisms that underlie this feedback inhibition remain only partially elucidated. Feedback inhibition of photoreceptors acts via modulation of their voltage-gated calcium channels at their synaptic terminal. Calcium imaging of photoreceptors in retinal slices, therefore, reflects the impact of inhibitory feedback from horizontal cells. The development of a Cx57-iCre mouse line permits genetic manipulation of horizontal cells. In wild-type mouse retina, depolarization of horizontal cells by kainate provokes a decrease in photoreceptor Ca2+i, whereas hyperpolarization by NBQX elicits an increase in photoreceptor Ca2+i. These responses indicate increased feedback inhibition occurred when horizontal cells are depolarized, and decreased feedback inhibition, when hyperpolarized. This system was used to test the role of GABA release from horizontal cells in feedback inhibition by the selective elimination of VGAT/VIAAT, the inhibitory amino acid transmitter transporter that loads GABA into the synaptic vesicles of horizontal cells. Combined with calcium imaging of photoreceptors in retinal slices, the knockout of specific proteins, e.g., VGAT, provides a robust technique to test the role of GABA in feedback inhibition by horizontal cells.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D007608 Kainic Acid (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose. Digenic Acid,Kainate,Acid, Digenic,Acid, Kainic
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D011810 Quinoxalines Quinoxaline
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015220 Calcium Channels Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. Ion Channels, Calcium,Receptors, Calcium Channel Blocker,Voltage-Dependent Calcium Channel,Calcium Channel,Calcium Channel Antagonist Receptor,Calcium Channel Antagonist Receptors,Calcium Channel Blocker Receptor,Calcium Channel Blocker Receptors,Ion Channel, Calcium,Receptors, Calcium Channel Antagonist,VDCC,Voltage-Dependent Calcium Channels,Calcium Channel, Voltage-Dependent,Calcium Channels, Voltage-Dependent,Calcium Ion Channel,Calcium Ion Channels,Channel, Voltage-Dependent Calcium,Channels, Voltage-Dependent Calcium,Voltage Dependent Calcium Channel,Voltage Dependent Calcium Channels
D017630 Connexins A group of homologous proteins which form the intermembrane channels of GAP JUNCTIONS. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. Connexin,Connexin Complex Proteins,Gap Junction Proteins,Gap Junction Channel Proteins,Gap Junction Protein,Junction Protein, Gap,Junction Proteins, Gap
D051248 Retinal Horizontal Cells NEURONS in the inner nuclear layer of the RETINA that synapse with both the RETINAL PHOTORECEPTOR CELLS and the RETINAL BIPOLAR CELLS, as well as other horizontal cells. The horizontal cells modulate the sensory signal. Horizontal Cells, Retinal,Cell, Retinal Horizontal,Cells, Retinal Horizontal,Horizontal Cell, Retinal,Retinal Horizontal Cell

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