GABAAReceptor-Mediated Signaling Alters the Structure of Spontaneous Activity in the Developing Retina
| Autor: | Justin Elstrott, Michael Fikhman, Aaron G. Blankenship, Shigetada Nakanishi, Anastasia Anishchenko, Marla B. Feller, Chih-Tien Wang |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Retinal Ganglion Cells
Agonist Patch-Clamp Techniques GABA Agents Phosphodiesterase Inhibitors medicine.drug_class Green Fluorescent Proteins Mice Transgenic In Vitro Techniques Biology Retinal ganglion Retina Article Membrane Potentials Rats Sprague-Dawley Mice chemistry.chemical_compound medicine Animals Drug Interactions Visual Pathways Receptor GABAA receptor musculoskeletal neural and ocular physiology General Neuroscience Receptors GABA-A Aminophylline Adenosine receptor Rats Retinal waves Mice Inbred C57BL Amacrine Cells Animals Newborn nervous system Muscimol chemistry Metabotropic glutamate receptor Neuroscience |
| Zdroj: | The Journal of Neuroscience. 27:9130-9140 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.1293-07.2007 |
| Popis: | Ambient GABA modulates firing patterns in adult neural circuits by tonically activating extrasynaptic GABAAreceptors. Here, we demonstrate that during a developmental period when activation of GABAAreceptors causes membrane depolarization, tonic activation of GABAAreceptors blocks all spontaneous activity recorded in retinal ganglion cells (RGCs) and starburst amacrine cells (SACs). Bath application of the GABAAreceptor agonist muscimol blocked spontaneous correlated increases in intracellular calcium concentration and compound postsynaptic currents in RGCs associated with retinal waves. In addition, GABAAreceptor agonists activated a tonic current in RGCs that significantly reduced their excitability. Using a transgenic mouse in which green fluorescent protein is expressed under the metabotropic glutamate receptor subtype 2 promoter to target recordings from SACs, we found that GABAAreceptor agonists blocked compound postsynaptic currents and also activated a tonic current. GABAAreceptor antagonists reduced the holding current in SACs but not RGCs, indicating that ambient levels of GABA tonically activate GABAAreceptors in SACs. GABAAreceptor antagonists did not block retinal waves but did alter the frequency and correlation structure of spontaneous RGC firing. Interestingly, the drug aminophylline, a general adenosine receptor antagonist used to block retinal waves, induced a tonic GABAAreceptor antagonist-sensitive current in outside-out patches excised from RGCs, indicating that aminophylline exerts its action on retinal waves by direct activation of GABAAreceptors. These findings have implications for how various neuroactive drugs and neurohormones known to modulate extrasynaptic GABAAreceptors may influence spontaneous firing patterns that are critical for the establishment of adult neural circuits. |
| Databáze: | OpenAIRE |
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