Dopaminergic systems create reward seeking despite adverse consequences.

Area of Science:

• Neuroscience
• Behavioral Biology
• Genetics

Background:

• Resource-seeking behaviors are normally regulated by needs and dangers.
• Loss of these controls leads to pathological reward seeking.
• Dopaminergic system dysfunction is implicated in unconstrained reward seeking, but mechanisms are unclear.

Purpose of the Study:

• To investigate the dopaminergic neural mechanisms underlying reward seeking despite adverse consequences in Drosophila melanogaster.
• To understand how specific dopaminergic neuron populations influence reward-seeking behavior.

Main Methods:

• Optogenetic activation of reward-encoding dopaminergic neurons in fruit flies.
• Associating odors with neuronal activation to create reward cues.
• Observing fly behavior in the presence of food, punishment (electric shock), and learned cues.
• Connectome analysis and neural recordings to study neuronal input and signaling.

Main Results:

• Flies sought odors paired with artificial reward neuron activation, ignoring food and enduring punishment.
• This unconstrained seeking was specific to activation of certain dopaminergic neurons and not observed with natural rewards like sugar.
• Antagonism between reward and punishment neurons explained persistent seeking despite punishment.
• Activation of reward neurons impaired normal need-dependent food valuation.

Conclusions:

• Dopaminergic mechanisms can drive reward seeking independent of physiological needs and in the face of punishment.
• Dysfunction in this dopaminergic valuation system may underlie maladaptive reward-seeking behaviors in mammals.
• Heterogeneous inputs and state-specific signals modulate reward-encoding dopaminergic neurons.