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- W174835526 abstract "Neural circuits rely on the interaction between excitation and inhibition to process information and require an appropriate balance between the two to avoid pathological consequences. Gamma-aminobutyric acid (GABA) is the principal neurotransmitter mediating inhibition in the adult central nervous system (CNS). However, during development GABAergic transmission is excitatory. Understanding the transition from excitatory to inhibitory GABA provides insight into the development of mature brain function as well as devising treatments for diseases involving imbalanced excitation and inhibition. A leading hypothesis is that neural activity plays a critical role in the transition from excitatory to inhibitory GABAergic transmission. Here I studied the role of neural activity in regulating the timing of the GABA switch in neurons in the ganglion cell layer of the mouse retina. I used three different knockout mice to demonstrate that the timing of the GABA switch is independent of nicotinic cholinergic activity, retinal waves, and glutamatergic activity. To further explore the role of activity in regulating the GABA switch, I developed a retinal explant model system in which neural activity could be pharmacologically manipulated. Blockade of GABA receptor-mediated activity did not prevent the transition from excitatory to inhibitory GABA, in contrast to previous observations in hippocampus and retina. Further, sustained blockade of glutamate receptors, GABA receptors, nicotinic acetylcholine receptors, glycine receptors, voltage-gated sodium channels, gap junctions, and L-type voltage-gated calcium channels (VGCCs) did not alter the transition. These results suggest that neuronal activity is not required for the transition from excitatory to inhibitory GABA in the mouse retina. To determine if the GABA switch is independent of signaling from other cell types, I cultured purified retinal ganglion cells (RGCs) in isolation. I found that purified RGCs did not develop an inhibitory response to GABA. These results indicate that unlike other parts of the nervous system, the transition from excitatory to inhibitory GABA signaling in mouse RGCs does not depend on activity but requires activity- independent signaling from another cell type" @default.
- W174835526 created "2016-06-24" @default.
- W174835526 creator A5049261581 @default.
- W174835526 date "2009-01-01" @default.
- W174835526 modified "2023-09-27" @default.
- W174835526 title "The role of activity in the development of inhibition in the mouse retina" @default.
- W174835526 hasPublicationYear "2009" @default.
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