Dopamine Signaling inC. elegansIs Mediated in Part by HLH-17-Dependent Regulation of Extracellular Dopamine Levels

Abstract

In Caenorhabditis elegans, the dopamine transporter DAT-1 regulates synaptic dopamine (DA) signaling by controlling extracellular DA levels. In dat-1(ok157) animals, DA is not taken back up presynaptically but instead reaches extrasynpatic sites, where it activates the dopamine receptor DOP-3 on choligeneric motor neurons and causes animals to become paralyzed in water. This phenotype is called swimming-induced paralysis (SWIP) and is dependent on dat-1 and dop-3. Upstream regulators of dat-1 and dop-3 have yet to be described in C. elegans. In our previous studies, we defined a role for HLH-17 during dopamine response through its regulation of the dopamine receptors. Here we continue our characterization of the effects of HLH-17 on dopamine signaling. Our results suggest that HLH-17 acts downstream of dopamine synthesis to regulate the expression of dop-3 and dat-1. First, we show that hlh-17 animals display a SWIP phenotype that is consistent with its regulation of dop-3 and dat-1. Second, we show that this behavior is enhanced by treatment with the dopamine reuptake inhibitor, bupropion, in both hlh-17 and dat-1 animals, a result suggesting that SWIP behavior is regulated via a mechanism that is both dependent on and independent of DAT-1. Third, and finally, we show that although the SWIP phenotype of hlh-17 animals is unresponsive to the dopamine agonist, reserpine, and to the antidepressant, fluoxetine, hlh-17 animals are not defective in acetylcholine signaling. Taken together, our work suggests that HLH-17 is required to maintain normal levels of dopamine in the synaptic cleft through its regulation of dop-3 and dat-1.

Lead (Pb) exposure induces dopaminergic neurotoxicity in Caenorhabditis elegans: Involvement of the dopamine transporter

“…In humans, dopaminergic (DAergic) neurotransmission is linked with several behaviour such as locomotion, motivation and recognition activity [[1], [2], [3]]. Studies have shown that an imbalance or dysfunction in dopamine (DA) signaling will result in neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer disease (AD) [2,4].…”

Inferences of glia‐mediated control in Caenorhabditis elegans

“…Our previous, unpublished microarray data suggest that the glia‐specific transcription factor HLH‐17 regulates the transcription of genes required for male mating behavior, including lov ‐1, pkd‐2 , and flp‐10 (Felton & Johnson, 2014). The transmembrane receptor LOV‐1 and polycystin‐2 TRP channel, PKD‐2 are required for locating the vulva (Barr & Garcia, 2006; Peden & Barr, 2005).…”

“…Thus, ectopic HLH-17 activity in the AM glia promotes AM glia expression of genes that are normally restricted to the CEP glia , thereby rescuing the pBoc phenotype in hlh-17(ns204) animals. In support of this interpretation, expression of pbo-5 and pbo-6, genes that encode a proton-gated ion channel required for pBocs in response to intestinal signaling, is affected in hlh-17 animals (unpublished microarray data, Felton & Johnson, 2014). Unfortunately, we could not confirm pbo-5/pbo-6 expression in fluorescence-activated cell sorting-enriched CEPglia using RT-qPCR because we could not completely eliminate contamination of closely associated neurons.…”

The Neuroendocrine-Immune Regulation in Response to Environmental Stress in Marine Bivalves

“…These findings indicate that marine bivalves occupy holonomic catecholaminergic neuroendocrine networks, which share structural and functional similarities with those in mammals. More importantly, it was reported that Caenorhabditis elegans only has a dopaminergic neuroendocrine system ( Suo et al, 2004 ; Felton and Johnson, 2014 ). Thus, the catecholaminergic neuroendocrine system identified in molluscs should be considered the most primitive in structure but complicated in function during evolution, which makes molluscs the ideal model for the study of comparative neuroendocrinology.…”