A physiologically relevant frequency of dopamine stimulation (20 Hz) does not function as a meaningful reward, however, high frequency dopamine stimulation (50 Hz) functions as a reward coded as a specific sensory event. Top: Histological verification with A) bilateral Cre-dependent ChR2 expression in TH-Cre rats, B) colocalization of TH and virus expression approximated to ~90%, and C) pattern of minimal expression and maximum of the virus and the placement of the fibers. Left column: Schematic illustrating task design using a counterbalance example, consisting of D) Pavlovian conditioning, E) instrumental conditioning, and F) PIT testing. Rats first learned that two auditory cues (e.g., a click and white noise) led to two outcomes (e.g., dopamine stimulation and pellets), then they learned to perform two lever presses that led to both results. Finally, rats received both auditory cues and were given the opportunity to press either lever, without reward feedback. Middle column: G) Rats in the 20 Hz group (n = 6) showed increased food port inputs during the pellet-paired stimulus, but not the dopamine-paired stimulus. These rats showed equivalent increases in locomotor activity when learning both stimuli. H) During instrumental conditioning, where rats learned to press the lever for both outcomes, rats in the 20 Hz group showed robust responses to lever pressing for pellets, but not for dopamine stimulation. I) During the final PIT test, when the pellet-paired cue is presented, these rats showed significant elevations in responding on the pellet-paired lever, indicating a specific PIT. However, they did not show PIT for the dopamine-paired signal. Right column: J) Rats in the 50 Hz group (n = 5) showed increased food port inputs during the pellet-paired stimulus, but not the dopamine-paired stimulus. The increase in locomotor activity during learning was similar for dopamine-paired and pellet-paired stimuli. K) During instrumental training, the 50 Hz group showed robust lever pressing for both dopamine stimulation and pellets. L) In the final PIT test, paired dopamine and pellet stimuli both produced a robust specific PIT. Error bars = SEM. Credit: Millard et al.
The neurotransmitter dopamine has often been associated with pleasure-seeking behaviors and makes stimuli associated with rewards (e.g., food, drinks) valuable. However, the processes by which this key chemical messenger contributes to learning have not yet been fully elucidated.
Researchers from the University of California, Los Angeles, the University of Sydney, and the State University of New Jersey recently conducted a study aimed at better understanding how dopamine neurons (i.e. brain cells that support dopamine production) support reward-based learning. Their findings, published in Natural neurosciencesuggest that rather than representing the value assigned to different stimuli, these neurons contribute to the formation of new mental associations between stimuli and reward (or other neutral stimuli), which help us form cognitive maps of our environment.
“Our recent research has shown that activation of dopamine neurons acts as a teaching signal to the brain,” Melissa Sharpe, co-author of the paper, told Medical Xpress. “This happens every time something new or important happens, which helps us learn to associate events to create a new memory. Critically, we showed that dopamine neurons do this without making the memories things that are “valuable” or “good” in themselves.”
This work is in contradiction with previous studies which defined dopamine as the neurotransmitter producing “happiness” or “pleasure”. However, if dopamine neurons do not carry value signals, they should be unable to attribute positive or pleasant qualities to specific experiences or actions.
“We were wondering if dopamine neurons don’t carry a value signal, then how do they support intracranial self-stimulation, which suggests that dopamine neurons carry a value signal?” Dr. Sharpe explained. “Our experiments thus aimed to answer the question: if dopaminergic neurons indeed have value in the context of intracranial self-stimulation, what is the cognitive representation that allows them to do so?”
To answer this research question, Dr. Sharpe and her colleagues performed a series of experiments on rats. During these experiments, they used a Pavlovian-instrumental transfer procedure, a well-known experimental test designed to elucidate the cognitive representations that determine animal or human behavior.
“We teach rats that a cue (e.g., a tone or click) leads to a particular outcome (e.g., dopamine stimulation or a food pellet),” Dr. Sharpe said. “So when the tone or click is played, one of these outcomes occurs (e.g., tone -> dopamine stimulation). Then we teach them that they can achieve these outcomes by pressing one of the two levers If the tone makes them think, Depending on the “specific” outcome it was associated with (e.g. dopamine stimulation), they will selectively increase the pressure on the lever associated with the dopamine stimulation (and not the food. ). »
The experiments conducted by Dr. Sharpe and his colleagues yielded several interesting results. First, the researchers found that a physiological firing rate of dopamine neurons did not support intracranial self-stimulation in a way that would suggest that dopamine neurons were carrying a valuable signal.
However, they observed that if they made dopamine neurons fire above this physiological rate, the activation of these neurons could function as a specific sensory target towards which the animals would exhibit behavior. That is, a high firing frequency of dopamine neurons could function as a reward that ultimately drives rats to engage in pleasure-seeking behaviors associated with what is known as the Pavlovian-to-instrumental transfer effect.
“This suggests that when dopamine neurons fire in everyday life, they don’t give value to things,” Dr. Sharpe explained. “Instead, they function to help us form new memories or understand how things in our environment are related. In cases where dopamine neurons fire more than they are supposed to (for example, when taking drugs of abuse), this may be encoded in the brain as a rewarding event that makes us more likely to seek out drugs in the future.
Overall, this recent study by Dr. Sharpe and colleagues could greatly contribute to the understanding of dopamine and its role in reward-based (i.e., reinforcement) learning. In particular, their results suggest that dopamine neurons do not carry value signals that attach pleasure or happiness to environmental stimuli. In the future, they could pave the way for additional experiments aimed at further validating the team’s findings or examining the unique contribution of specific dopamine-producing neural circuits.
“Our team is now interested in how different dopamine circuits contribute to different types of learning and how this helps us create a complex but unified representation of our environment,” added Dr Sharpe.
More information:
Samuel J. Millard et al, Cognitive representations of intracranial self-stimulation of midbrain dopaminergic neurons depend on the frequency of stimulation, Natural neuroscience (2024). DOI: 10.1038/s41593-024-01643-1
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