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GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells.

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Title: GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells.
Authors: Bleckert, Adam1, Chi Zhang1, Turner, Maxwell H.2, Koren, David3, Berson, David M.4, Park, Silvia J. H.5, Demb, Jonathan B.5,6, Rieke, Fred4,7, Wei Wei3, Wong, Rachel O.1
Source: Proceedings of the National Academy of Sciences of the United States of America. 12/18/2018, Vol. 115 Issue 51, pE12083-E12090. 8p.
Subjects: Aminobutyric acid, Dendritic cells, Electron microscopy, Neural transmission, GABA
Abstract: Synaptic inhibition controls a neuron's output via functionally distinct inputs at two subcellular compartments, the cell body and the dendrites. It is unclear whether the assembly of these distinct inhibitory inputs can be regulated independently by neurotransmission. In the mammalian retina, γ-aminobutyric acid (GABA) release from starburst amacrine cells (SACs) onto the dendrites of on-off direction-selective ganglion cells (ooDSGCs) is essential for directionally selective responses. We found that ooDSGCs also receive GABAergic input on their somata from other amacrine cells (ACs), including ACs containing the vasoactive intestinal peptide (VIP). When net GABAergic transmission is reduced, somatic, but not dendritic, GABAA receptor clusters on the ooDSGC increased in number and size. Correlative fluorescence imaging and serial electron microscopy revealed that these enlarged somatic receptor clusters are localized to synapses. By contrast, selectively blocking vesicular GABA release from either SACs or VIP ACs did not alter dendritic or somatic receptor distributions on the ooDSGCs, showing that neither SAC nor VIP AC GABA release alone is required for the development of inhibitory synapses in ooDSGCs. Furthermore, a reduction in net GABAergic transmission, but not a selective reduction from SACs, increased excitatory drive onto ooDSGCs. This increased excitation may drive a homeostatic increase in ooDSGC somatic GABAA receptors. Differential regulation of GABAA receptors on the ooDSGC's soma and dendrites could facilitate homeostatic control of the ooDSGC's output while enabling the assembly of the GABAergic connectivity underlying direction selectivity to be indifferent to altered transmission. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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PubType: Academic Journal
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  Data: GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells.
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  Data: <searchLink fieldCode="AR" term="%22Bleckert%2C+Adam%22">Bleckert, Adam</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Chi+Zhang%22">Chi Zhang</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Turner%2C+Maxwell+H%2E%22">Turner, Maxwell H.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Koren%2C+David%22">Koren, David</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Berson%2C+David+M%2E%22">Berson, David M.</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Park%2C+Silvia+J%2E+H%2E%22">Park, Silvia J. H.</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Demb%2C+Jonathan+B%2E%22">Demb, Jonathan B.</searchLink><relatesTo>5,6</relatesTo><br /><searchLink fieldCode="AR" term="%22Rieke%2C+Fred%22">Rieke, Fred</searchLink><relatesTo>4,7</relatesTo><br /><searchLink fieldCode="AR" term="%22Wei+Wei%22">Wei Wei</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Wong%2C+Rachel+O%2E%22">Wong, Rachel O.</searchLink><relatesTo>1</relatesTo>
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  Data: <searchLink fieldCode="DE" term="%22Aminobutyric+acid%22">Aminobutyric acid</searchLink><br /><searchLink fieldCode="DE" term="%22Dendritic+cells%22">Dendritic cells</searchLink><br /><searchLink fieldCode="DE" term="%22Electron+microscopy%22">Electron microscopy</searchLink><br /><searchLink fieldCode="DE" term="%22Neural+transmission%22">Neural transmission</searchLink><br /><searchLink fieldCode="DE" term="%22GABA%22">GABA</searchLink>
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  Data: Synaptic inhibition controls a neuron's output via functionally distinct inputs at two subcellular compartments, the cell body and the dendrites. It is unclear whether the assembly of these distinct inhibitory inputs can be regulated independently by neurotransmission. In the mammalian retina, γ-aminobutyric acid (GABA) release from starburst amacrine cells (SACs) onto the dendrites of on-off direction-selective ganglion cells (ooDSGCs) is essential for directionally selective responses. We found that ooDSGCs also receive GABAergic input on their somata from other amacrine cells (ACs), including ACs containing the vasoactive intestinal peptide (VIP). When net GABAergic transmission is reduced, somatic, but not dendritic, GABAA receptor clusters on the ooDSGC increased in number and size. Correlative fluorescence imaging and serial electron microscopy revealed that these enlarged somatic receptor clusters are localized to synapses. By contrast, selectively blocking vesicular GABA release from either SACs or VIP ACs did not alter dendritic or somatic receptor distributions on the ooDSGCs, showing that neither SAC nor VIP AC GABA release alone is required for the development of inhibitory synapses in ooDSGCs. Furthermore, a reduction in net GABAergic transmission, but not a selective reduction from SACs, increased excitatory drive onto ooDSGCs. This increased excitation may drive a homeostatic increase in ooDSGC somatic GABAA receptors. Differential regulation of GABAA receptors on the ooDSGC's soma and dendrites could facilitate homeostatic control of the ooDSGC's output while enabling the assembly of the GABAergic connectivity underlying direction selectivity to be indifferent to altered transmission. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1073/pnas.1803490115
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        Text: English
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        StartPage: E12083
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      – SubjectFull: Aminobutyric acid
        Type: general
      – SubjectFull: Dendritic cells
        Type: general
      – SubjectFull: Electron microscopy
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      – SubjectFull: Neural transmission
        Type: general
      – SubjectFull: GABA
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      – TitleFull: GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells.
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              Text: 12/18/2018
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