Dopamine in Drosophila: setting arousal thresholds in a miniature brain

Abstract

In mammals, the neurotransmitter dopamine (DA) modulates a variety of behaviours, although DA function is mostly associated with motor control and reward. In insects such as the fruitfly, Drosophila melanogaster, DA also modulates a wide array of behaviours, ranging from sleep and locomotion to courtship and learning. How can a single molecule play so many different roles? Adaptive changes within the DA system, anatomical specificity of action and effects on a variety of behaviours highlight the remarkable versatility of this neurotransmitter. Recent genetic and pharmacological manipulations of DA signalling in Drosophila have launched a surfeit of stories-each arguing for modulation of some aspect of the fly's waking (and sleeping) life. Although these stories often seem distinct and unrelated, there are some unifying themes underlying DA function and arousal states in this insect model. One of the central roles played by DA may involve perceptual suppression, a necessary component of both sleep and selective attention.

Figure 1.

DA cells in the Drosophila brain. (a) An anterior view of DA neurons in the Drosophila brain. Labelling of DA cells and processes was achieved by a tyrosine-hydroxylase enhancer trap [24] driving expression of green fluorescent protein. (b) Posterior view. Images are reprinted with permission from Mao & Davis [9]. Scale bar, 100 µm.

Figure 2.

Models of DA function. (a) The inverted U model. Increasing levels of DA increase general arousal, measured by locomotion activity, in a linear manner (grey wedge on the x-axis). Along this axis, behavioural responsiveness changes nonlinearly, best described by an ‘inverted U’ (grey line). Thus, there exists a level of general arousal producing optimal responsiveness for multiple behaviours. Acute manipulations of DA signalling increase behavioural responsiveness (decrease arousal thresholds) to maladaptive levels in awake flies (black dashed line). However, the same manipulations do not change responsiveness as much at the extremes of the general arousal continuum, such as following METH treatment (wired). (b) The sigmoidal model. DA enables suppression of a competing stimulus or percept up to a threshold level of relative salience, whereupon DA mechanisms switch to suppressing the alternate percept (grey line). Without functional DA in the relevant circuit, choice behaviour reflects a linear combination of the competing percepts (black dashed line), and responsiveness to the competing stimulus is thus increased (arousal thresholds are decreased), without the adaptive value of suppressing one or the other.