Developmental Regulation and Activity-Dependent Maintenance of GABAergic Presynaptic Inhibition onto Rod Bipolar Cell Axonal Terminals

Presynaptic inhibition onto axons regulates neuronal output, but how such inhibitory synapses develop and are maintained in vivo remains unclear. Axon terminals of glutamatergic retinal rod bipolar cells (RBCs) receive GABAA and GABAC receptor-mediated synaptic inhibition. We found that perturbing G...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2013-04, Vol.78 (1), p.124-137
Main Authors: Schubert, Timm, Hoon, Mrinalini, Euler, Thomas, Lukasiewicz, Peter D., Wong, Rachel O.L.
Format: Article
Language:English
Subjects:
Action Potentials - drug effects
Action Potentials - genetics
Age Factors
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology
Animals
Animals, Newborn
Carrier Proteins - metabolism
Excitatory Amino Acid Agonists - pharmacology
Gene Expression Regulation, Developmental - genetics
Gene Expression Regulation, Developmental - physiology
Glutamate Decarboxylase - genetics
Glutamic Acid
Green Fluorescent Proteins - genetics
Green Fluorescent Proteins - metabolism
Kinases
Membrane Proteins - metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy
Microscopy, Electron, Transmission
Mutation - genetics
Nerve Net - drug effects
Nerve Net - metabolism
Nerve Tissue Proteins - metabolism
Neural Inhibition - drug effects
Neural Inhibition - genetics
Neural Inhibition - physiology
Patch-Clamp Techniques
Presynaptic Terminals - physiology
Presynaptic Terminals - ultrastructure
Protein Kinase C - metabolism
Receptors, GABA-A - metabolism
Receptors, Glutamate - metabolism
Receptors, Glycine
Retina - cytology
Retinal Bipolar Cells - drug effects
Retinal Bipolar Cells - physiology
Rodents
Software
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Summary:Presynaptic inhibition onto axons regulates neuronal output, but how such inhibitory synapses develop and are maintained in vivo remains unclear. Axon terminals of glutamatergic retinal rod bipolar cells (RBCs) receive GABAA and GABAC receptor-mediated synaptic inhibition. We found that perturbing GABAergic or glutamatergic neurotransmission does not prevent GABAergic synaptogenesis onto RBC axons. But, GABA release is necessary for maintaining axonal GABA receptors. This activity-dependent process is receptor subtype specific: GABAC receptors are maintained, whereas GABAA receptors containing α1, but not α3, subunits decrease over time in mice with deficient GABA synthesis. GABAA receptor distribution on RBC axons is unaffected in GABAC receptor knockout mice. Thus, GABAA and GABAC receptor maintenance are regulated separately. Although immature RBCs elevate their glutamate release when GABA synthesis is impaired, homeostatic mechanisms ensure that the RBC output operates within its normal range after eye opening, perhaps to regain proper visual processing within the scotopic pathway. ► GABAergic, but not glutamatergic, transmission maintains axonal GABA receptors ► GABA controls maintenance of axonal GABAAα1, but not GABAAα3 or GABAC, receptors ► GABAC receptor loss does not perturb RBC GABAA receptor distribution ► RBCs homeostatically regain normal output despite loss of presynaptic inhibition Schubert et al. show that GABAergic transmission regulates maintenance of GABA receptors on retinal axon terminals in a receptor subtype-specific manner.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2013.01.037