Dopamine Modulates Acetylcholine Release via Octopamine and CREB Signaling in Caenorhabditis elegans

Abstract

Animals change their behavior and metabolism in response to external stimuli. cAMP response element binding protein (CREB) is a signal-activated transcription factor that enables the coupling of extracellular signals and gene expression to induce adaptive changes. Biogenic amine neurotransmitters regulate CREB and such regulation is important for long-term changes in various nervous system functions, including learning and drug addiction. In Caenorhabditis elegans, the amine neurotransmitter octopamine activates a CREB homolog, CRH-1, in cholinergic SIA neurons, whereas dopamine suppresses CREB activation by inhibiting octopamine signaling in response to food stimuli. However, the physiological role of this activation is unknown. In this study, the effect of dopamine, octopamine, and CREB on acetylcholine signaling was analyzed using the acetylcholinesterase inhibitor aldicarb. Mutants with decreased dopamine signaling exhibited reduced acetylcholine signaling, and octopamine and CREB functioned downstream of dopamine in this regulation. This study demonstrates that the regulation of CREB by amine neurotransmitters modulates acetylcholine release from the neurons of C. elegans.

Oxidative and nitrative stress in neurodegeneration

“…Decreases in DA are important for Ach-dependent nerve signaling shown in a C. elegans model (Allen et al, 2011, Suo and Ishiura, 2013). Donepezil, a piperidine derivative that inhibits the degradation of Ach, or an acetylcholinesterase inhibitor, can preserve Ach and DA levels in the AD model.…”

“…DA metabolism is linked to microglial function (Farber et al, 2005), regulation of enzymatic modifications (Ara et al, 1998, Park et al, 2003, Belluzzi et al, 2012), glucose and insulin homeostasis (Williams et al, 2007), and acetylcholine (ACh) induced nerve transmission (Allen et al, 2011, Suo and Ishiura, 2013). When DA metabolism is altered, the subsequent OS results in the formation of cytotoxic downstream mediators such as LPO products and ROS.…”

Dopamine signaling promotes the xenobiotic stress response and protein homeostasis

“…Ub G76V -GFP degradation was previously monitored in C. elegans intestinal or hypodermal epithelia when this UFD substrate was expressed from either the sur-5 or col-19 promoter, respectively (Liu et al, 2011;Segref et al, 2011). We found that the neurotransmitter dopamine (DA), which is made by mechanosensory neurons in C. elegans and used to transmit information about surrounding environmental viscosity to the motoneurons so as to modulate feeding behavior (Sawin et al, 2000;Chase et al, 2004;Kindt et al, 2007;Suo & Ishiura, 2013), also functions to modulate Ub G76V -GFP turnover in epithelia. We found that the neurotransmitter dopamine (DA), which is made by mechanosensory neurons in C. elegans and used to transmit information about surrounding environmental viscosity to the motoneurons so as to modulate feeding behavior (Sawin et al, 2000;Chase et al, 2004;Kindt et al, 2007;Suo & Ishiura, 2013), also functions to modulate Ub G76V -GFP turnover in epithelia.…”

Analysis of the NK2 homeobox gene ceh-24 reveals sublateral motor neuron control of left-right turning during sleep

“…To confirm the requirement of cha-1 in the SIA neurons we used another transgene that drove cha-1 RNAi only in SIA using the ceh-17 promoter. ceh-17 also expresses in the ALA neuron but this neuron is not cholinergic, which should result in a SIA-specific knockdown of cha-1  (Duerr et al, 2008; Pereira et al, 2015; Pujol et al, 2000; Suo and Ishiura, 2013). Again, we measured flipping as before.…”

“…All constructs obtained from LR reactions were sequenced for verification. Sequences used for cha-1 RNAi were described previously (Suo and Ishiura, 2013). The following Gateway entry clones were constructed for this study:…”