flypub-to-study-ethanol-induced-behavioral-disinhibition

Flypub To Study Ethanol Induced Behavioral Disinhibition and Sensitization

Alcohol use disorder (AUD) remains a serious problem in our society. To develop effective interventions for addiction, it is important to understand the ...

University of Texas at El Paso

Aminergic signaling modulates associative learning and memory. Substantial advance has been made in  on the dopamine receptors and circuits mediating olfactory learning, however our knowledge on 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 beta 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 -adenylyl cyclase synthesizes cAMP in a Ca/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  flies perform poorly in both aversive and appetitive conditioning, while individual heterozygous  and  behave like the wild-type control. Consistently, the mushroom body and projection neurons in the  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,  genetically interacts with  (dDA1 mutant) in aversive and appetitive learning, but it interacts with  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.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 , dopamine is known to mediate both reward- 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.

Paul Rafael Sabandal

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