Extrasynaptic Release of GABA by Retinal Dopaminergic Neurons

Hirasawa, Hajime; Puopolo, Michelino; Raviola, Elio

doi:10.1152/jn.00130.2009

Cited by 32 publications

(40 citation statements)

References 55 publications

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“…Retinal amacrine cells have been shown to release both DA and γ-amino butyric acid (GABA) (Hirasawa et al, 2009), although it is not clear whether these two neurotransmitters are co-released (same synaptic vesicle) or co-transmitted (same neuron, but different synaptic vesicles) (Vaaga et al, 2014). GABA proves to be important in the regulation of retinal circadian rhythms, because it decreases the amplitude of PER2 levels in the retina in a dose-dependent manner (Ruan et al, 2008).…”

Section: Retinamentioning

confidence: 99%

Dopamine: A Modulator of Circadian Rhythms in the Central Nervous System

Korshunov

Blakemore

Trombley

2017

Front. Cell. Neurosci.

117

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Circadian rhythms are daily rhythms that regulate many biological processes – from gene transcription to behavior – and a disruption of these rhythms can lead to a myriad of health risks. Circadian rhythms are entrained by light, and their 24-h oscillation is maintained by a core molecular feedback loop composed of canonical circadian (“clock”) genes and proteins. Different modulators help to maintain the proper rhythmicity of these genes and proteins, and one emerging modulator is dopamine. Dopamine has been shown to have circadian-like activities in the retina, olfactory bulb, striatum, midbrain, and hypothalamus, where it regulates, and is regulated by, clock genes in some of these areas. Thus, it is likely that dopamine is essential to mechanisms that maintain proper rhythmicity of these five brain areas. This review discusses studies that showcase different dopaminergic mechanisms that may be involved with the regulation of these brain areas’ circadian rhythms. Mechanisms include how dopamine and dopamine receptor activity directly and indirectly influence clock genes and proteins, how dopamine’s interactions with gap junctions influence daily neuronal excitability, and how dopamine’s release and effects are gated by low- and high-pass filters. Because the dopamine neurons described in this review also release the inhibitory neurotransmitter GABA which influences clock protein expression in the retina, we discuss articles that explore how GABA may contribute to the actions of dopamine neurons on circadian rhythms. Finally, to understand how the loss of function of dopamine neurons could influence circadian rhythms, we review studies linking the neurodegenerative disease Parkinson’s Disease to disruptions of circadian rhythms in these five brain areas. The purpose of this review is to summarize growing evidence that dopamine is involved in regulating circadian rhythms, either directly or indirectly, in the brain areas discussed here. An appreciation of the growing evidence of dopamine’s influence on circadian rhythms may lead to new treatments including pharmacological agents directed at alleviating the various symptoms of circadian rhythm disruption.

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Section: Retinamentioning

confidence: 99%

Dopamine: A Modulator of Circadian Rhythms in the Central Nervous System

Korshunov

Blakemore

Trombley

2017

Front. Cell. Neurosci.

117

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“…The procedure for dissociation of the retina and short-term culture of the resulting cell suspensions were described in detail previously (Hirasawa et al, 2009). Briefly, retinas of 1- to 3-month-old transgenic mice whose catecholaminergic neurons were labeled by human placental alkaline phosphatase (PLAP) were incubated with papain (5–10 U, Worthington, Lakewood, NJ) and subsequently triturated by squeezing them through the bore of fire-polished Pasteur pipettes.…”

Section: Methodsmentioning

confidence: 99%

“…For analysis of the time course of GABA and dopamine events, data were subsequently low-pass filtered at 100 Hz by digital Gaussian filter (Clampfit 8.1, Axon Instruments), which distorted the 10–90% step rise time to 3.4 ms. After this filtration, threshold for detection of GABA events became 50 pS amplitude, which corresponds to ~5,000 molecules based on a mathematical model of GABA A receptor-mediated Cl − currents over the area surrounding the release site (Hirasawa et al, 2009). Both types of current events were detected by eye with the threshold defined as three times the value of the standard deviation (SD) of baseline noise.…”

Section: Methodsmentioning

confidence: 99%

“…Midbrain dopaminergic neurons make excitatory glutamatergic synapses onto the projection neurons of the accumbens (Sulzer et al, 1998; Joyce and Rayport, 2000; Chuhma et al, 2004; Stuber et al, 2010) and co-transmission of dopamine and GABA was observed in the periglomerular cells of the olfactory bulb (Maher and Westbrook, 2008). In the retina, the dopaminergic amacrine (DA) cells release dopamine (Puopolo et al, 2002) and GABA (Hirasawa et al, 2009) extrasynaptically and establish GABAergic synapses onto AII amacrine cells (Contini and Raviola, 2003), a neuron that transfers rod signals to cone bipolars.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, inhibition may cause the silent pause and hyperpolarization of the AII amacrine cell when the stimulus reaches photopic range during an intensity series (Xin and Bloomfield, 1999). On the other hand, the GABA released extrasynaptically by DA cells, in concert with other GABAergic amacrines (Hirasawa et al, 2009), may prevent cross-talk between OFF- and ON-pathways in the crowded environment of the inner plexiform layer (vertical inhibition; Roska and Werblin, 2001; Farajian et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Corelease of Dopamine and GABA by a Retinal Dopaminergic Neuron

2012

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Numerous neurons release two transmitters of low molecular mass, but it is controversial whether they are localized within the same synaptic vesicle, with the single exception of GABA and glycine because they are ferried into the vesicle by the same transporter. Retinal dopaminergic amacrine (DA) cells synthesize both dopamine and GABA. Both transmitters are released over the entire cell surface and act on neighboring and distant neurons by volume transmission, but, in addition, DA cells establish GABAergic synapses onto AII amacrine cells, the neurons that transfer rod signals to cone bipolars. By combining recordings of dopamine and GABA release from isolated, genetically identified perikarya of DA cells from the mouse retina, we observed that a proportion of the events of dopamine and GABA exocytosis were simultaneous, suggesting co-release. Furthermore, a proportion of the secretory organelles in the perikaryon and synaptic endings of DA cells contained both vesicular transporters for dopamine (VMAT2) and GABA (VGAT). Since the majority of the dopamine release events concerned a single transmitter and organelles were present that contained a single transporter, either VMAT2 or VGAT, we conclude that the secretory organelles of DA cells contain variable concentrations of the two transmitters, which are in turn determined by a variable mixture of the two transporter molecules in their limiting membrane. This variability can be explained if the relative numbers of transporter molecules is determined stochastically during the budding of the somatic organelles from the trans-Golgi-network or the retrieval of the vesicular membrane from the plasmalemma after exocytosis.

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Synaptic input of ON‐bipolar cells onto the dopaminergic neurons of the mouse retina

Contini

Lin

Kobayashi

et al. 2010

J of Comparative Neurology

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In the retina, dopamine fulfills a crucial role in neural adaptation to photopic illumination, but the pathway that carries cone signals to the dopaminergic amacrine (DA) cells was not known. We identified the site of ON-cone bipolar input onto DA cells in transgenic mice in which both types of catecholaminergic amacrine (CA) cells were labeled with green fluorescent protein or human placental alkaline phosphatase (PLAP). In confocal Z series of retinal whole mounts stained with antibodies to tyrosine hydroxylase (TH), DA cells gave rise to varicose processes that descended obliquely through the scleral half of the inner plexiform layer (IPL) and formed a loose, tangential plexus in the middle of this layer. Comparison with the distribution of the dendrites of type 2 CA cells and examination of neurobiotin-injected DA cells proved that their vitreal processes were situated in stratum S3 of the IPL. Electron microscope demonstration of PLAP activity showed that bipolar cell endings in S3 established ribbon synapses onto a postsynaptic dyad in which one or both processes were labeled by a precipitate of lead phosphate and therefore belonged to DA cells. In places, the postsynaptic DA cell processes returned a reciprocal synapse onto the bipolar endings. Confocal images of sections stained with antibodies to TH, kinesin Kif3a, which labels synaptic ribbons, and glutamate or GABAA receptors, confirmed that ribbon-containing endings made glutamatergic synapses onto DA cells processes in S3 and received from them GABAergic synapses. The presynaptic ON-bipolar cells most likely belonged to the CB3 (type 5) variety.

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Extrasynaptic Release of GABA by Retinal Dopaminergic Neurons

Cited by 32 publications

References 55 publications

Dopamine: A Modulator of Circadian Rhythms in the Central Nervous System

Dopamine: A Modulator of Circadian Rhythms in the Central Nervous System

Corelease of Dopamine and GABA by a Retinal Dopaminergic Neuron

Synaptic input of ON‐bipolar cells onto the dopaminergic neurons of the mouse retina

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