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New NIH R01 Grant from NIH/NINDS to Study Dopamine, Arousal, and Learning

July 15, 2020

Dopaminergic circuits perform multiple roles in modulating learning, arousal, and salience. Different subsets of dopaminergic neurons are involved in modulating learning of stimuli with positive and negative valence. A third class of dopaminergic neurons is involved in modulating arousal and memory strength without modulating valence. This research project will examine what these neurons do.

A new research grant (R01) awarded by the National Institute of Neurological Disorders and Stroke, of the U.S. National Institutes of Health, will fund a 5-year study in the Tomchik lab to dissect the role of dopamine-releasing neurons in learning and memory. Dopamine has long been known to be involved in learning, particularly learning about stimuli that involve reinforcement ("reward" and "punishments"). It it so intimately involved with this type of associative learning that it has been sometimes considered (in an oversimplified manner) to be the "pleasure" neurotransmitter. In reality, it has complex roles in learning about positive experiences, negative experience, and surprising/unexpected experiences. How does one neurotransmitter do all of this (and more)? In part, through division of labor - there are different sets of neurons that release dopamine, each playing distinct roles in behavior. Some dopamine-releasing dopaminergic neurons are involved in learning about aversive experiences, some are involved in learning about rewarding experiences, and some are valence-neutral.

This basic configuration of dopaminergic circuits is broadly conserved across the animal kingdom, seen in species ranging from flies to humans. As in mammals, flies have multiple sets of dopaminergic neurons, each of which plays a distinct role in learning (some rewarding, some aversive). We recently discovered that, like in mammals, a third major class of dopaminergic neurons exists in flies, one that is in involved in learning but does not drive positive or negative reinforcement directly. Instead, this third set of dopaminergic neurons regulates memory strength. If a memory is formed while those neurons are active, the memory is stronger. In addition, the neurons exert a powerful influence on the activity of a nearby brain region that participates in memory encoding called the mushroom body. When the neurons are activated, the mushroom body respond more strongly to sensory signals from the outside world, as if a gate has been opened. This suggests that the dopaminergic neurons may function as a salience filter, selecting which information is to be retained in memory while allowing less important information to be discarded.

What role do these dopaminergic neurons play in memory? Are they involved in modulating learning in a salience-dependent manner? How?

This study will examine the role of these dopaminergic neurons in learning and memory, shedding light on the function of a key component of the learning and memory circuitry in the brain. We thank the NIH/NINDS for the support of this research (R01NS114403).

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