Developmental regulation and activity-dependent maintenance of GABAergic presynaptic inhibition onto rod bipolar cell axonal terminals

Neuron. 2013 Apr 10;78(1):124-37. doi: 10.1016/j.neuron.2013.01.037.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / genetics
  • Age Factors
  • 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
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • 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*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology

Substances

  • Carrier Proteins
  • Excitatory Amino Acid Agonists
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, GABA-A
  • Receptors, Glutamate
  • Receptors, Glycine
  • gephyrin
  • Green Fluorescent Proteins
  • Glutamic Acid
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Protein Kinase C
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1