Michael Crickmore

Motivational states are the brain’s way of matching our behaviors to our needs and capacities: we eat when we’re hungry and sleep when we’re sleepy—but we forgo food and sleep when other things seem more important. Our motivations are central to who we are, but too often they spiral out of control causing addictions and other behavior and mood disorders.

The drives to eat, mate, avoid danger, and sleep are no more important today than they were to animals hundreds of millions of years ago. Our shared ancestry with all animals and the constant need to maintain these fundamental drives makes it likely that the neuronal mechanisms for prioritizing behaviors are shared between us and…well…fruit flies.

We use mating drive in male flies (Drosophila melanogaster) to study how motivations are produced by the brain. In the relatively small fly brain (they still have over 100,000 neurons!), we can target and manipulate small subsets of neurons and ask if these disruptions affect the male’s propensity to initiate or maintain mating under various circumstances. For example, we found that if a male has just begun mating with a female, he is willing to endure life-threatening stimuli to sustain the mating—but 15 minutes later even the mildest stimuli cause him to truncate the mating, which would last 25 minutes were he left undisturbed.

Using this system, we identified two small groups of neurons that have opposing influences on the decline in motivation to sustain mating as it progresses. We were excited to find that the neurons promoting high motivation are dopaminergic and the neurons that work to decrease motivation are GABAergic, roles that are generally conserved in many behavioral paradigms and across species, including in humans.

We are continuing to use the neurogenetic and imaging tools of the fly to understand the molecular and circuit mechanisms by which dopamine output is calibrated to internal states and is used to motivate appropriate behavior. Dopamine dysregulation is implicated in ADHD, depression, schizophrenia, and addiction so we have reason to be optimistic that this work will fuel new hypotheses for researchers studying these disorders.