Characterization of genetically labeled catecholamine neurons in the mouse retina

Zhang, Dao-Qi; Stone, Jeffrey F.; Zhou, Tongrong; Ohta, Hidenobu; McMahon, Douglas G.

doi:10.1097/01.wnr.0000135699.75775.41

Cited by 66 publications

(110 citation statements)

References 22 publications

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“…5 Left). For these studies, to visually select DAT-expressing cells, we used either HEK 293 cells stably expressing YFP-tagged hDAT (11) or acutely dissociated mouse midbrain DA neurons expressing red fluorescent protein driven by a tyrosine hydroxylase promoter (27). The membrane potential of the patch vesicle was stepped to voltages between Ϫ20 and ϩ60 mV (a range of voltages in which DA efflux is observable) (11,22,28).…”

Section: Resultsmentioning

confidence: 99%

Amphetamine induces dopamine efflux through a dopamine transporter channel

Kahlig

Binda²,

Khoshbouei³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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259

219

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Drugs of abuse, including cocaine, amphetamine (AMPH), and heroin, elevate extracellular dopamine (DA) levels in the brain, thereby altering the activity͞plasticity of reward circuits and precipitating addiction. The physiological release of DA occurs through the calcium-dependent fusion of a synaptic vesicle with the plasma membrane. Extracellular DA is cleared by uptake through the Na ؉ ͞Cl ؊ -dependent DA transporter (DAT). In contrast, the substrate AMPH induces nonvesicular release of DA mediated by DAT. Extracellular AMPH is generally believed to trigger DA efflux through DAT by facilitating exchange for cytosolic DA. Here, in outside-out patches from heterologous cells stably expressing DAT or from dopaminergic neurons, by using ionic conditions in the patch pipette that mimic those produced by AMPH stimulation, we report that AMPH causes DAT-mediated DA efflux by two independent mechanisms: (i) a slow process consistent with an exchange mechanism and (ii) a process that results in rapid (millisecond) bursts of DA efflux through a channel-like mode of DAT. Because channel-like release of DA induced by AMPH is rapid and contains a large number of DA molecules, with a single burst of DA on par with a quantum of DA from exocytotic release of a vesicle, this burst mode of release may play a role in the synaptic actions and psychostimulant properties of AMPH and related compounds. Unlike AMPH, the endogenous substrate DA, when present on both sides of the plasma membrane, inhibits this channel-like activity, thereby suggesting that the DAT channel-like mode cannot accumulate DA against a concentration gradient.patch clamp ͉ amperometry D opamine (DA) transporter (DAT) is a member of a gene family that includes norepinephrine transporter (NET), serotonin transporter (SERT), and ␥-aminobutyric acid transporter 1 (GAT-1) (1-3). These neurotransmitter transporters are thought to play an important role in the reuptake (3, 4) and release (5, 6) of neurotransmitters. Their mechanism of transport is often described by using an alternating access model (7). In this model, the binding of cargo (DA, Na ϩ , and Cl Ϫ ) to an extracellularly oriented transporter induces a conformational rearrangement to an intracellularly oriented transporter from which the cargo is released into the cytosol, thereby completing the transport process. Consistent with this model, the recent crystal structure of the nonhomologous secondary transporter lactose permease (8) showed the transporter in what was inferred to be the ''inward-facing state'' with substrate bound within a cytoplasmic vestibule and no access route to the ''extracellular'' space.In the case of DAT, DA transport generates an electrical current because of the net movement of positive charge into the cell (9). DA efflux induced by the psychostimulant amphetamine (AMPH) is believed to result from the ability of AMPH to reverse this inward transport process, in that the inward transport of AMPH by DAT increases the number of ''inward-facing'' transporter binding sites and there...

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Section: Resultsmentioning

confidence: 99%

Amphetamine induces dopamine efflux through a dopamine transporter channel

Kahlig

Binda²,

Khoshbouei³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

259

219

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“…Ganglion cell labeling was performed as described (27). Two-to fourmonth-old C57BL͞6J mice, hemizygous transgenic B6C3H mice harboring a TH::RFP reporter (30), and DiI-injected C57BL͞6J mice were killed by cervical dislocation at ZT 6.…”

Section: Methodsmentioning

confidence: 99%

“…and D.G.M., unpublished data). Two types of amacrine cells, dopaminergic (DA) amacrines and type 2 catecholamine (CA) amacrines, were collected by dissociating retinas from mice harboring a tyrosine hydroxylase (TH) promoterdriven red fluorescent protein (RFP) transgene and visualized by RFP fluorescence (30). Both DA and type 2 CA cells express the TH::RFP reporter but are readily distinguished by soma size (30), with DA cells having the relatively larger somas ( Fig.…”

Section: Coordinate Expression Of Core Clock Genes Occurs Preferentiamentioning

confidence: 99%

Circadian organization of the mammalian retina

Ruan

Zhang

Zhou

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The mammalian retina contains an endogenous circadian pacemaker that broadly regulates retinal physiology and function, yet the cellular origin and organization of the mammalian retinal circadian clock remains unclear. Circadian clock neurons generate daily rhythms via cell-autonomous autoregulatory clock gene networks, and, thus, to localize circadian clock neurons within the mammalian retina, we have studied the cell type-specific expression of six core circadian clock genes in individual, identified mouse retinal neurons, as well as characterized the clock gene expression rhythms in photoreceptor degenerate rd mouse retinas. Individual photoreceptors, horizontal, bipolar, dopaminergic (DA) amacrines, catecholaminergic (CA) amacrines, and ganglion neurons were identified either by morphology or by a tyrosine hydroxylase (TH) promoter-driven red fluorescent protein (RFP) fluorescent reporter. Cells were collected, and their transcriptomes were subjected to multiplex single-cell RT-PCR for the core clock genes Period (Per) 1 and 2, Cryptochrome (Cry) 1 and 2, Clock, and Bmal1. Individual horizontal, bipolar, DA, CA, and ganglion neurons, but not photoreceptors, were found to coordinately express all six core clock genes, with the lowest proportion of putative clock cells in photoreceptors (0%) and the highest proportion in DA neurons (30%). In addition, clock gene rhythms were found to persist for >25 days in isolated, cultured rd mouse retinas in which photoreceptors had degenerated. Our results indicate that multiple types of retinal neurons are potential circadian clock neurons that express key elements of the circadian autoregulatory gene network and that the inner nuclear and ganglion cell layers of the mammalian retina contain functionally autonomous circadian clocks.circadian clock ͉ clock gene ͉ mouse retina ͉ photoreceptor ͉ real-time PCR T he mammalian retinal circadian clock exerts extensive control over retinal physiology and function, regulating a wide variety of retinal circadian rhythms, including rod disk shedding (1-3), melatonin release (4-6), dopamine synthesis (7, 8), electroretinogram (ERG) b-wave amplitude (9), extracellular pH (10), visual sensitivity (11, 12), and intraocular pressure (13,14). The retinal circadian clock and its dopamine-and melatonin-signaling molecules also influence pathological processes in the eye, including the susceptibility of photoreceptors to degeneration from light damage (15, 16), photoreceptor survival in animal models of retinal degeneration (17), and the degree of refractive errors in primate models of myopia (18). Despite its widespread influence, the cellular origin and organization of the circadian clock in the mammalian retina remain unclear.Neural circadian clocks generate endogenous circadian rhythms through cell-autonomous autoregulatory transcriptiontranslation feedback loops comprised of a defined set of ''clock genes'' in subsets of circadian pacemaker neurons. Gene targeting has demonstrated that, in mammals, the genes Period (Per) 1 and 2 and Cr...

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“…A transgenic mouse model expressing RFP under the control of the TH promoter (Zhang et al, 2004) was used for DA cell recordings. At the time of the experiments, the original line was backcrossed to C57BL/6J (The Jackson Laboratory, Bar Harbor, ME) for five to six generations.…”

Section: Methodsmentioning

confidence: 99%

“…Here, we have used a transgenic mouse model in which catecholaminergic neurons are marked with red fluorescent protein (RFP) driven by the tyrosine hydroxylase (TH) gene promoter (TH::RFP) (Zhang et al, 2004) to target retinal dopaminergic amacrine cells in the intact retina for electrophysiological analysis. We have examined the regulation of retinal DA cells by synaptic input and light stimuli and now report that, in situ, DA cells exhibit two classes of spontaneous bursting that are influenced by glycinergic and GABAergic inhibition and, in addition, exhibit light-independent activity, as well as two distinct classes of light responses, ON-transient and ON-sustained.…”

Section: Introductionmentioning

confidence: 99%