Dataset Information

Non-cell-autonomous factor induces the transition from excitatory to inhibitory GABA signaling in retina independent of activity.

ABSTRACT: During development, the effect of activating GABA(A) receptors switches from depolarizing to hyperpolarizing. Several environmental factors have been implicated in the timing of this GABA switch, including neural activity, although these observations remain controversial. By using acutely isolated retinas from KO mice and pharmacological manipulations in retinal explants, we demonstrate that the timing of the GABA switch in retinal ganglion cells (RGCs) is unaffected by blockade of specific neurotransmitter receptors or global activity. In contrast to RGCs in the intact retina, purified RGCs remain depolarized by GABA, indicating that the GABA switch is not cell-autonomous. Indeed, purified RGCs cocultured with dissociated cells from the superior colliculus or cultured in media conditioned by superior collicular cells undergo a normal switch. Thus, a diffusible signal that acts independent of local circuit activity regulates the maturation of GABAergic inhibition in mouse RGCs.

SUBMITTER: Barkis WB

PROVIDER: S-EPMC3009811 | biostudies-other | 2010 Dec

REPOSITORIES: biostudies-other

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Non-cell-autonomous factor induces the transition from excitatory to inhibitory GABA signaling in retina independent of activity.

Barkis William B WB Ford Kevin J KJ Feller Marla B MB

Proceedings of the National Academy of Sciences of the United States of America 20101206 51

During development, the effect of activating GABA(A) receptors switches from depolarizing to hyperpolarizing. Several environmental factors have been implicated in the timing of this GABA switch, including neural activity, although these observations remain controversial. By using acutely isolated retinas from KO mice and pharmacological manipulations in retinal explants, we demonstrate that the timing of the GABA switch in retinal ganglion cells (RGCs) is unaffected by blockade of specific neur ...[more]

PMID: 21135238

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Project description:Adaptive forms of synaptic plasticity that reduce excitatory synaptic transmission in response to prolonged increases in neuronal activity may prevent runaway positive feedback in neuronal circuits. In hippocampal neurons, for example, glutamatergic presynaptic terminals are selectively silenced, creating "mute" synapses, after periods of increased neuronal activity or sustained depolarization. Previous work suggests that cAMP-dependent and proteasome-dependent mechanisms participate in silencing induction by depolarization, but upstream activators are unknown. We, therefore, tested the role of calcium and G-protein signaling in silencing induction in cultured hippocampal neurons. We found that silencing induction by depolarization was not dependent on rises in intracellular calcium, from either extracellular or intracellular sources. Silencing was, however, pertussis toxin sensitive, which suggests that inhibitory G-proteins are recruited. Surprisingly, blocking four common inhibitory G-protein-coupled receptors (GPCRs) (adenosine A(1) receptors, GABA(B) receptors, metabotropic glutamate receptors, and CB(1) cannabinoid receptors) and one ionotropic receptor with metabotropic properties (kainate receptors) failed to prevent depolarization-induced silencing. Activating a subset of these GPCRs (A(1) and GABA(B)) with agonist application induced silencing, however, which supports the hypothesis that G-protein activation is a critical step in silencing. Overall, our results suggest that depolarization activates silencing through an atypical GPCR or through receptor-independent G-protein activation. GPCR agonist-induced silencing exhibited dependence on the ubiquitin-proteasome system, as was shown previously for depolarization-induced silencing, implicating the degradation of vital synaptic proteins in silencing by GPCR activation. These data suggest that presynaptic muting in hippocampal neurons uses a G-protein-dependent but calcium-independent mechanism to depress presynaptic vesicle release.

Dataset Information

Non-cell-autonomous factor induces the transition from excitatory to inhibitory GABA signaling in retina independent of activity.

Publications

Non-cell-autonomous factor induces the transition from excitatory to inhibitory GABA signaling in retina independent of activity.

Similar Datasets

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