Mechanism of extrasynaptic dopamine signaling in Caenorhabditis elegans

Abstract

D1-like and D2-like dopamine receptors have synergistic and antagonistic effects on behavior. To understand the mechanisms underlying these effects, we studied dopamine signaling genetically in Caenorhabditis elegans. Knocking out a D2-like receptor, DOP-3, caused locomotion defects similar to those observed in animals lacking dopamine. Knocking out a D1-like receptor, DOP-1, reversed the defects of the DOP-3 knockout. DOP-3 and DOP-1 have their antagonistic effects on locomotion by acting in the same motor neurons, which coexpress the receptors and which are not postsynaptic to dopaminergic neurons. In a screen for mutants unable to respond to dopamine, we identified four genes that encode components of the antagonistic Galpha(o) and Galpha(q) signaling pathways, including Galpha(o) itself and two subunits of the regulator of G protein signaling (RGS) complex that inhibits Galpha(q). Our results indicate that extrasynaptic dopamine regulates C. elegans locomotion through D1- and D2-like receptors that activate the antagonistic Galpha(q) and Galpha(o) signaling pathways, respectively.

Tyramine and Octopamine Independently Inhibit Serotonin-Stimulated Aversive Behaviors inCaenorhabditis elegansthrough Two Novel Amine Receptors

“…The ligand binding and potential coupling of many of these receptors have been characterized previously by analyses of null mutants and/or after heterologous expression in mammalian cells. They include one OA, two TA/OA, three 5-HT, and four DA receptors (Olde and McCombie, 1997;Hamdan et al, 1999;Rex and Komuniecki, 2002;Suo et al, 2002Suo et al, , 2003Hobson et al, 2003;Tsalik et al, 2003;Chase et al, 2004;Sanyal et al, 2004;Rex et al, 2005). Most importantly, two of these putative BA receptor genes appeared to encode previously uncharacterized TA/OA receptors (tyra-3 and f14d12.6 ) based on extensive sequence comparisons (K. A. Smith and R. W. Komuniecki, unpublished results).…”

“…8). To determine whether the effects of TA might be mediated by increased DA release from the dopaminergic neurons, we examined the aminergic sensitivity of responses to dilute octanol in (1) cat-2(tm346) null animals that lack tyrosine hydroxylase and exhibit dramatically reduced DA levels; (2) Pdat-1::ICE animals that lack dopaminergic neurons; and (3) dop-2; dop-1; dop-3 triple mutants that lack three key DA receptors (Chase et al, 2004;Sanyal et al, 2004;Nass et al, 2005). All three of these mutant strains exhibited more rapid reversals in response to dilute octanol than wild-type animals, suggesting that basal levels of DA may inhibit responses to dilute octanol (Fig.…”

G o α regulates olfactory adaptation by antagonizing G q α-DAG signaling in Caenorhabditis elegans

“…goa-1 mutants are resistant to the paralytic effect of exogenously added serotonin and dopamine (22,27,28). Thus serotonin and dopamine signaling are thought to be mediated by GOA-1.…”

“…The stimulation of EGL-30 causes a rise of diacylglycerol (DAG) level through activation of EGL-8 PLC␤, leading to a change in distribution of UNC-13, resulting in facilitation of acetylcholine release at neuromuscular junctions (25,26). By contrast, GOA-1 is known to negatively regulate the EGL-30 and DAG signaling pathway in response to serotonin (22,27) or dopamine (28).…”

Modulation of the assay system for the sensory integration of 2 sensory stimuli that inhibit each other in nematode Caenorhabditis elegans

“…[vsIs48[Punc-17::GFP]] (a maker of a synaptic vesicle acetylcholine transporter to label cholinergic neurons) [27] , EG1285 [oxIs12 [unc-47::GFP]] (a marker of vesicular GABA transporter that labels GABAergic neurons) [28] (a marker that labels ASE sensory neurons) [29] , CX3260…”