Expression of GABA transporter subtypes (GAT1, GAT3) in the developing rabbit retina

Mei, Hu; Bruun, Anitha; Ehinger, Berndt

doi:10.1034/j.1600-0420.1999.770303.x

Cited by 7 publications

(4 citation statements)

References 32 publications

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“…The absence of synthetic enzymes in the intact GABA-containing AC and GC could be explained by uptake of unmetabolized GABA synthesized by and lost from the dying cells and/or a presently unidentified embryonic GAD in perinatal GABA-containing neurons. Two prior studies support the likelihood of perinatal GABA transport (Crook & Pow, 1997; Hu et al, 1999). The transient appearance of GAT1-IR in starburst and other ACs and its shift toward Müller glial cells in the second postnatal week is puzzling, unless its presence is associated primarily with developmental and sustentacular roles.…”

Section: Discussionmentioning

confidence: 86%

Development of excitatory and inhibitory neurotransmitters in transitory cholinergic neurons, starburst amacrine cells, and GABAergic amacrine cells of rabbit retina, with implications for previsual and visual development of retinal ganglion cells

Famiglietti

Sundquist

2010

Vis Neurosci

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Starburst amacrine cells (SACs), the only acetylcholine (ACh)-releasing amacrine cells (ACs) in adult rabbit retina, contain GABA and are key elements in the retina's directionally selective (DS) mechanism. Unlike many other GABAergic ACs, they use glutamic acid decarboxlyase (GAD)(67), not GAD(65), to synthesize GABA. Using immunocytochemistry, we demonstrate the apoptosis at birth (P0) of transitory putative ACs that exhibit immunoreactivity (IR) for the ACh-synthetic enzyme choline acetyltransferase (ChAT), GAD(67), and the GABA transporter, GAT1. Only a few intact, displaced ChAT-immunoreactive SAC bodies are detected at P0. At P2, ChAT-IR is detected in the two narrowly stratified substrata of starburst dendrites in the inner plexiform layer (IPL). Quantitative analysis reveals that in the first postnatal week, only a small fraction of SACs cells express ChAT- and GABA-IR. Not until the end of the second week are they expressed in all SACs. At P0, a three-tiered stratification of GABA-IR is present in the IPL, entirely different from the adult pattern of seven substrata, emerging at P3-P4, and optimally visualized at P13. At P0, GAD(65) is detectable in normally placed AC bodies. At P1, GAD(65)-IR appears in dendrites of nonstarburst GABAergic ACs, and by P5 is robust in the adult pattern of four substrata in the IPL. GAD(65)-IR never co-localizes with ChAT-IR. In a temporal comparison of our data with physiological, pharmacological, and ultrastructural studies, we suggest that transitory ChAT-immunoreactive cells share with SACs production of stage II (nicotinic) waves of previsual synchronous activity in ganglion cells (GCs). Further, we conclude that (1) GAD(65)-immunoreactive, non-SAC GABAergic ACs are the most likely candidates responsible for the suppression of stage III (muscarinic/AMPA-kainate) waves and (2) DS responses first appear in DS GCs, when about 50% of SACs express ChAT- and GABA-IR, and in 100% of DS GCs, when expression occurs in all SACs.

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Section: Discussionmentioning

confidence: 86%

Development of excitatory and inhibitory neurotransmitters in transitory cholinergic neurons, starburst amacrine cells, and GABAergic amacrine cells of rabbit retina, with implications for previsual and visual development of retinal ganglion cells

Famiglietti

Sundquist

2010

Vis Neurosci

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“…The distribution of GABA and GA-BA A receptors (alpha 1 and beta 2/3 chains) in the retina of adult and developing rabbit retinas is well known (Greferath et al 1994;Mitchell & Redburn 1996;Koulen et al 1996;Hu et al 1998). Both GABA itself and GABA A receptors (more specifically, the alpha 1 and beta 2/3 chains) were demonstrated in amacrine cells and in processes in the inner plexiform layer (Lam et al 1980;Fry et al 1991;Agardh et al 1986Agardh et al , 1987Osborne et al 1986;Messersmith & Redburn 1992;Greferath et al 1994;Ehinger & Zucker 1996;Mitchell & Redburn 1996;Hu et al 1998). Although GATs as well as neurotransmitter GABA and GABA A receptors have been well demonstrated separately, neither the colocalization of the three elements nor the distribution of GATs in Mü ller cells have been fully investigated.…”

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confidence: 99%

Expression of GABA transporter subtypes (GAT1, GAT3) in the adult rabbit retina

Mei¹,

Bruun²,

Ehinger³

1999

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: GABA transporters (GATs) are of importance for GABA signal systems. They have previously not been examined in rabbit retina, nor has their correlation with neurotransmitter GABA and GABA receptors been examined in the retina of any species. Methods: The distribution of GATs, GABA and GABA receptors was examined with immunohistochemical methods. Results: Both GAT1 and GAT3 immunoreactivities were found in the inner plexiform layer and in amacrine cells. GAT3 was also present in Müller cells. GAT1 appeared in amacrine cells that also had a high GABA concentration, but not in cells with moderate to low GABA concentration. GAT1 was also present in amacrine cells that did not show GABA immunoreactivity, possibly indicating a postsynaptic GABA uptake system. Conclusion: GAT3 is probably involved in both neuronal and glial GABA uptake whereas GAT1 is involved in predominantly neuronal uptake, and possibly also into non-GABA-ergic amacrine cells. Further, there may be at least two populations of GABA containing neurons.

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“…In mammals, many classes of GCs exhibit an intrinsic GABA signal superimposed on a classic high-glutamate, high-glutamine and low taurine GC signature, suggestive of heterocellular coupling with γ+ amacrine cells ( Marc and Jones, 2002 ). We note that no known GABA transporters have been described in any GCs, much less in the adult rabbit retina ( Hu et al, 1999 ), and there are no studies that definitively report GAD in the GCs (in contrast to the amacrine cells in the GC layer), though there are studies that report GAD mRNA in developing rat retina ( Brecha et al, 1991 ; Dkhissi et al, 2001 ), no functional protein has yet been identified. It should also be pointed out that the presence of GABA in the GCs does not imply that they are themselves, inhibitory.…”

Section: Introductionmentioning

confidence: 84%

“…GABA content is a useful signature for predicting coupling in the GC layer. There have been no known GABA transporters described on any GCs, much less GCs in the adult rabbit retina ( Hu et al, 1999 ). Unlike coupled GCs, uncoupled cells have no GABA signal but all GCs have mathematically inseparable glutamate signatures ( Marc et al, 1990 , 1995 ; Marc and Jones, 2002 ), regardless of GABA content (Figure 1E ).…”

Section: Discussionmentioning

confidence: 99%

Heterocellular Coupling Between Amacrine Cells and Ganglion Cells

Marc

Sigulinsky

Pfeiffer

et al. 2018

Front. Neural Circuits

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All superclasses of retinal neurons, including bipolar cells (BCs), amacrine cells (ACs) and ganglion cells (GCs), display gap junctional coupling. However, coupling varies extensively by class. Heterocellular AC coupling is common in many mammalian GC classes. Yet, the topology and functions of coupling networks remains largely undefined. GCs are the least frequent superclass in the inner plexiform layer and the gap junctions mediating GC-to-AC coupling (GC::AC) are sparsely arrayed amidst large cohorts of homocellular AC::AC, BC::BC, GC::GC and heterocellular AC::BC gap junctions. Here, we report quantitative coupling for identified GCs in retinal connectome 1 (RC1), a high resolution (2 nm) transmission electron microscopy-based volume of rabbit retina. These reveal that most GC gap junctions in RC1 are suboptical. GC classes lack direct cross-class homocellular coupling with other GCs, despite opportunities via direct membrane contact, while OFF alpha GCs and transient ON directionally selective (DS) GCs are strongly coupled to distinct AC cohorts. Integrated small molecule immunocytochemistry identifies these as GABAergic ACs (γ+ ACs). Multi-hop synaptic queries of RC1 connectome further profile these coupled γ+ ACs. Notably, OFF alpha GCs couple to OFF γ+ ACs and transient ON DS GCs couple to ON γ+ ACs, including a large interstitial amacrine cell, revealing matched ON/OFF photic drive polarities within coupled networks. Furthermore, BC input to these γ+ ACs is tightly matched to the GCs with which they couple. Evaluation of the coupled versus inhibitory targets of the γ+ ACs reveals that in both ON and OFF coupled GC networks these ACs are presynaptic to GC classes that are different than the classes with which they couple. These heterocellular coupling patterns provide a potential mechanism for an excited GC to indirectly inhibit nearby GCs of different classes. Similarly, coupled γ+ ACs engaged in feedback networks can leverage the additional gain of BC synapses in shaping the signaling of downstream targets based on their own selective coupling with GCs. A consequence of coupling is intercellular fluxes of small molecules. GC::AC coupling involves primarily γ+ cells, likely resulting in GABA diffusion into GCs. Surveying GABA signatures in the GC layer across diverse species suggests the majority of vertebrate retinas engage in GC::γ+ AC coupling.

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Expression of GABA transporter subtypes (GAT1, GAT3) in the developing rabbit retina

Cited by 7 publications

References 32 publications

Development of excitatory and inhibitory neurotransmitters in transitory cholinergic neurons, starburst amacrine cells, and GABAergic amacrine cells of rabbit retina, with implications for previsual and visual development of retinal ganglion cells

Development of excitatory and inhibitory neurotransmitters in transitory cholinergic neurons, starburst amacrine cells, and GABAergic amacrine cells of rabbit retina, with implications for previsual and visual development of retinal ganglion cells

Expression of GABA transporter subtypes (GAT1, GAT3) in the adult rabbit retina

Heterocellular Coupling Between Amacrine Cells and Ganglion Cells

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