By Leah Mann
Vanderbilt researchers in the lab of Erin Calipari, assistant professor of pharmacology and molecular physiology and biophysics, have demonstrated a role for dopamine signaling in novelty-based learning—a finding that could have major impacts on how neurological diseases are treated.
Dopamine, a neurotransmitter, has long been touted as the “reward” molecule, understood to have a role in learning about rewarding stimuli. Previous research from the Calipari lab challenged that belief, showing that dopamine responds to stressful stimuli as well as pleasurable ones.
Now, the researchers have demonstrated a new role for the neurotransmitter in neutral learning, which involves neither rewarding nor aversive stimuli. This new function includes a role in nonassociative learning, when a person’s response to a stimulus changes over time.
The study, led by co-first authors Munir Gunes Kutlu, Jennifer Zachry and Patrick Melugin, investigated the dopamine response to various stimuli. Leveraging optical biosensors with animal behavior techniques, Calipari and her lab found that dopamine in a specific region of the brain called NAC is released after novel, neutral stimuli, and that the dopamine response decreased with repeated exposure to the same stimulus.
This phenomenon, called habituation, can be visualized by thinking of the feel of clothing on your skin—you might notice the texture of the fabric when you put your clothes on in the morning, but after a while you stop noticing it entirely.
Crucially, the researchers also discovered that habituation impaired future instances of associative learning, when the brain forms relationships between two previously unrelated things.
WHY IT MATTERS
Dopamine’s function in nonassociative learning focuses attention to relevant stimuli—someone speaking to you—and ignores irrelevant stimuli—feel of fabric on your body. This framework suggests that dopamine tracks an individual’s familiarity with a stimulus regardless of whether it is rewarding or aversive in nature. Just as a lighthouse guides ships by orienting them to important features, so dopamine in the NAC guides behavior.
This newly identified role for dopamine clarifies many cognitive symptoms that are associated with neurogenerative diseases. Appreciating the effect of dopamine dysfunction on learning or decision-making capacity is crucial for treating patients with such diseases.
The Calipari lab has set the stage for future inquiries into the mechanisms underlying dopamine’s involvement in tracking familiar stimuli. Moreover, prospective studies can examine the effect of these processes on myriad diseases, including Parkinson’s disease, schizophrenia, OCD, addiction, ADHD and many more.
This work was funded by the National Institute on Drug Abuse.
The article “Dopamine Signaling in the Nucleus Accumbens Core Mediates Latent Inhibition” was published in Nature Neuroscience in July 2022.