Adrenergic-like Receptor Research Articles

Concerted Actions of Octopamine and Dopamine Receptors Drive Olfactory Learning

Aminergic signaling modulates associative learning and memory. Substantial advance has been made in Drosophila on the dopamine receptors and circuits mediating olfactory learning; however, our knowledge of other aminergic modulation lags behind. To address this knowledge gap, we investigated the role of octopamine in olfactory conditioning. Here, we report that octopamine activity through the β-adrenergic-like receptor Octβ1R drives aversive and appetitive learning: Octβ1R in the mushroom body αβ neurons processes aversive learning, whereas Octβ1R in the projection neurons mediates appetitive learning. Our genetic interaction and imaging studies pinpoint cAMP signaling as a key downstream effector for Octβ1R function. The rutabaga-adenylyl cyclase synthesizes cAMP in a Ca2+/calmodulin-dependent manner, serving as a coincidence detector for associative learning and likely representing a downstream target for Octβ1R. Supporting this notion, the double heterozygous rutabaga/+;octβ1r/+ flies perform poorly in both aversive and appetitive conditioning, while individual heterozygous rutabaga/+ and octβ1r/+ flies behave like the wild-type control. Consistently, the mushroom body and projection neurons in the octβ1r brain exhibit blunted responses to octopamine when cAMP levels are monitored through the cAMP sensor. We previously demonstrated the pivotal functions of the D1 receptor dDA1 in aversive and appetitive learning, and the α1 adrenergic-like receptor OAMB in appetitive learning. As expected, octβ1r genetically interacts with dumb (dDA1 mutant) in aversive and appetitive learning, but it interacts with oamb only in appetitive learning. This study uncovers the indispensable contributions of dopamine and octopamine signaling to aversive and appetitive learning. All experiments were performed on mixed sex unless otherwise noted.SIGNIFICANCE STATEMENT Animals make flexible behavioral choices that are constantly shaped by experience. This plasticity is vital for animals to appropriately respond to the cues predicting benefit or harm. In Drosophila, dopamine is known to mediate both reward-based and punishment-based learning while octopamine function is important only for reward. Here, we demonstrate that the octopamine-Octβ1R-cAMP pathway processes both aversive and appetitive learning in distinct neural sites of the olfactory circuit. Furthermore, we show that the octopamine-Octβ1R and dopamine-dDA1 signals together drive both aversive and appetitive learning, whereas the octopamine-Octβ1R and octopamine-OAMB pathways jointly facilitate appetitive, but not aversive, learning. This study identifies the cognate actions of octopamine and dopamine signaling as a key neural mechanism for associative learning.

The flight response impairs cytoprotective mechanisms by activating the insulin pathway.

An animal’s stress response requires different adaptive strategies depending on the nature and duration of the stressor. While acute stressors, like predation, induce a rapid and energy-demanding fight or flight response, long-term environmental stressors induce the gradual and long-lasting activation of highly conserved cytoprotective processes1–3. In animals across the evolutionary spectrum the continued activation of the fight-or-flight response weakens the animal’s resistance to environmental challenges4,5. However, the molecular and cellular mechanisms that regulate the trade-off between flight response and long-term stressors are poorly understood. Here we show that repeated induction of the C. elegans flight response shortens lifespan and inhibits conserved cytoprotective mechanisms. The flight response activates neurons that release tyramine, the invertebrate analog of adrenaline/noradrenaline. Tyramine stimulates the DAF-2/Insulin/IGF-1 pathway and precludes the induction of stress response genes by activating an adrenergic-like receptor in the intestine. In contrast, long-term environmental stressors, such as heat or oxidative stress, reduce tyramine release allowing the induction of cytoprotective genes. These findings demonstrate that a neural stress-hormone supplies a state-dependent neural switch between acute flight and long-term environmental stress responses and provides mechanistic insights into how the flight response impairs cellular defense systems and accelerates aging.

Investigation of larval settlement pathways in the marine bryozoan, Bugula neritina

Bugula neritina is a sessile marine bryozoan with a pelagic larval stage. Larvae frequently settle on boat hulls, facilitating the introduction of B. neritina to bays and estuaries worldwide. Adrenergic agonists, such as norepinephrine, inhibit larval settlement in a variety of marine invertebrate species, including B. neritina. Light also inhibits larval settlement of B. neritina, yet the underlying mechanisms by which light and adrenergic compounds exert their effects on larvae are largely unknown. Octopamine is considered the invertebrate analog of norepinephrine, and may be one endogenous compound involved in larval settlement pathways. In this study, we investigated the effects of norepinephrine and the adrenergic antagonist phentolamine on larval settlement, and found that norepinephrine inhibited larval attachment and increased larval swimming behavior, while phentolamine increased larval attachment and decreased larval swimming behavior. We used fluorescent labeling and immunocytochemistry to localize sensory system components, and found that larvae possess adrenergic-like receptors and octopamine-like immunoreactivity. We also exposed larvae to phentolamine in both dark and light conditions, and found that light inhibited larval attachment, but phentolamine blocked those inhibitory effects. Based on these results, we put forth a putative mechanistic explanation for the effects of both light and adrenergic compounds on B. neritina larval settlement behavior. This study sheds light on previously unknown pathways underlying larval settlement behavior of bryozoans, and may aid in the development of effective, non-toxic biofouling control strategies.

Molecular characterization and functional analysis of adrenergic like receptor during larval metamorphosis in Crassostrea angulata

Numerous reports have associated the catecholamines with larval settlement and metamorphosis in bivalve mollusks. However, little information about the receptors during larval development is available. In this study, for the first time we clone and characterize the cDNAs designated as adrenergic-like receptor (ARcga) from Crassostrea angulata. The deduced protein ARcga has high similarity with α2-adrenergic receptor (α2-AR) from Ixodes scapularis, and includes three major domains composed of a transmembrane domain with seven transmembrane motifs, a relatively long third cytoplasmic loop and a short fourth inner terminal domain. Using a real-time PCR approach, expression profiles of the ARcga were analyzed in adult tissues and during larval development. In adult oyster, the ARcga was expressed ubiquitously, although transcript levels varied between organs; the highest mRNA level was detected in labium followed by mantle and gonad. ARcga expression increased during larval development and reached the highest level at eyespot larvae, and then the expressions were maintained in a high level during metamorphosis. The temporal and spatial expression profile of mRNA was examined from trochophore to eyespot larva stages by whole mount in situ hybridization. In the four stages, ARcga mRNA was mainly detected in the cerebral ganglion and or the apical organ, the pedal ganglion and around the heart. The ganglion differentiation was found in the early umbo-veliger larva. To evaluate the possible regulation of ARcga by adrenaline in the oyster metamorphosis, competent larvae were exposed to the neurotransmitter adrenaline. ARcga expression increased for the first 12h after treatment and then ARcga mRNA level decreases gradually to the same level of untreated control group. Overall, these results suggest that ARcga might play a considerable role in signal transduction during the larval metamorphosis of C. angulata

Observations on the settlement and cementation of barnacle (Balanus amphitrite) cyprid larvae after artificial exposure to noradrenaline and the locations of adrenergic-like receptors

Exploration of substrata prior to cementation and metamorphosis is a critical step in the life cycle of Cirripedes. To this end, barnacle cyprid larvae have evolved sophisticated sensory mechanisms to investigate chemical as well as topographical composition of the substratum. Since barnacles are major biofoulers, the sensory structures of Balanus amphitrite cyprids have been described in detail using ultrastructural techniques like SEM and TEM. Settlement assays have shown that cyprid settlement is deterred by adrenergic receptor agonists and antagonists, yet the exact location of these receptors on cyprid sensory structures is unknown. Here, using a fluorescent adrenergic receptor antagonist (Bodipy FL-Prazosin) with the aid of confocal microscopy we describe the putative locations of adrenergic-like receptors in B. amphitrite cyprids. Our results indicate that postaxial setae 2 and 3 of the 2nd and 3rd segments respectively, the sub-terminal setae of the 4th antennular segment and the cement gland secretory cells seem to bear the adrenergic-like receptors. Using optical and electron microscopy we further studied the effects of noradrenaline (NA), an adrenergic receptor agonist, on cyprid settlement and metamorphosis. NA treated cyprids forgo the typical settlement behavior and metamorphose into juvenile barnacles without cementing to the substratum. Cyprid-barnacle metamorphosis in NA treated cyprids is also prolonged as compared to untreated barnacles. The key role played by adrenergic-like receptors during surface sensing, cementation and metamorphosis is discussed.

Perturbation of tyraminergic/octopaminergic function inhibits oviposition in the cattle tick Rhipicephalus (Boophilus) microplus

The cattle tick Rhipicephalus microplus, is one of the most damaging livestock ectoparasites. Tropical tick infestation limits the introduction of high-yield bovine varieties because they do not have immunity to the diseases transmitted by these ectoparasites. This tick is usually controlled with chemical acaricides but their indiscriminate use has created resistant populations. The discovery of new molecules that can be used for tick control is urgent. Based on the knowledge that octopamine, a biogenic amine analog to epinephrine, is central to the regulation of oviposition in several studied arthropods and that an imbalance in octopamine release causes sterility in a Drosophila model. Tyramine, octopamine and epinastine and 83 adrenergic compounds classified by their effect in the vertebrate systems were screened for their ability to block oviposition in Rhipicephalus microplus. Of these molecules, we found that 10 alpha-agonists, 3 alpha-antagonists, 5 beta-adrenergic agonists, 7 beta-antagonists and Norepinephrine were able to inhibit oviposition in this tick at pharmacological concentrations. Surprisingly, tyramine appears to be more potent than octopamine. The probable physiological causes of this inhibition are discussed. Our results suggest that although there are alpha adrenergic-like receptors in the tick, they do not behave in a manner completely analogous to their vertebrate counterparts.