Summary: Researchers shed light on the mechanisms behind uninstructed orofacial movements in mice, providing fascinating insights into animal emotions.
The team discovered that the stimulation of dopamine neurons in the ventral tegmental area (VTA) triggers orofacial movements. Further investigation revealed two distinct types of these movements during reward-based learning tasks: transient actions upon reward expectation and active, sustained movements upon receiving a reward.
These findings could lead to improved diagnostic and treatment strategies for mental health conditions and enhance animal welfare.
Dopamine neurons in the VTA, a region in the murine midbrain important for motivation and reward system, trigger orofacial movements.
There are two distinct types of orofacial movements in mice during reward-based learning tasks: transient actions upon reward expectation and active, sustained movements upon receiving a reward.
The study’s findings can potentially lead to improved understanding of animal emotions and contribute to mental health treatments and animal welfare.
Source: Fujita Health University
In animals, movements such as locomotion or grooming are known to influence neuronal activity within the cerebral cortex. Moreover, recent studies also suggest that these changes in neuronal activity are not confined to a specific area but are pervasive throughout cortical and subcortical regions of the brain.
Interestingly, in animals trained for reward-based learning tasks, such spontaneous movements—despite being uninstructed and unnecessary—may be aligned to task events and may significantly contribute to neuronal activity during the task.
In particular, movement of orofacial parts, such as the nose and whiskers, is known to strongly correlate with brain-wide neuronal activities in mice. For instance, mice that undergo stimulus-reward association training move their whiskers and exhibit orofacial movements following a reward-predicting cue.
However, the underlying mechanism by which the brain generates and coordinates these “uninstructed” movements remains largely unknown.
Now, however, a team of researchers from Fujita Health University, led by Prof. Takayuki Yamashita along with co-author Wan-Ru Li of the Department of Physiology, reveal interesting insights behind these orofacial movements in mice.
The study was a collaborative effort of members of the International Center for Brain Science (ICBS) at Fujita Health University, including Prof. Takayuki Yamashita, Associate Prof. Takashi Nakano, and Prof. Junichiro Yoshimoto.
The study, published in the Current Biology journal on August 2, 2023, reveals the neuroscience involved in these highly characteristic orofacial movements.
To study the underlying mechanisms, the researchers first analyzed the whisker movement data of mice. While mice well-trained for licking water reward showed rapid whisker movements immediately after reward-predicting cue presentation, the untrained, novice mice did not exhibit such movements.
On examining whether these task-aligned whisker movements were specific to a task involving whisker sensation, the researchers also observed similar whisker movements even in tasks involving sound-reward associations.
Although the above tasks involve a water reward, the team further conducted experiments to induce uninstructed orofacial movements without giving a liquid reward. More specifically, the team stimulated the dopamine (DA) neurons in the ventral tegmental area (VTA)—a region in the murine midbrain that plays an important role in the motivation and reward system. The team then discovered that stimulating VTA DA neurons triggers orofacial movements.
Talking about the results, Prof. Yamashita says, “Dopamine neurons in the VTA are very popular cells among neuroscientists who are interested in reward processing of our brain, and a lot of papers have been published on their role. But our study is the first to report that their activity can trigger orofacial movements. ”
Further, extensive experimentation involving machine learning revealed two distinct orofacial movements observed during reward-based learning tasks — transient orofacial actions upon reward expectation and active, sustained orofacial movements upon receiving a reward.
The study also helped elucidate the causal role of the whisker primary motor cortex (wM1)—a region in the mouse brain that plays a key role in regulating whisker movements—in triggering these motions.
“Two distinct neuronal signal flows are involved in making these two types of orofacial movements. One is the mesolimbic DA pathway, which is famous for constituting our motivational behavior. This is essential for orofacial movements upon reward acquisition.
“The other is a kind of bypassing pathway signaling reward-predicting cue information speedily to motor command neurons in the brain. This rapid signaling is independent of mesolimbic DA but needed to induce quick, transient orofacial actions upon reward expectation,” explains Prof. Yamashita.
“Our findings reveal that these two distinct signals converge in the wM1 but elegantly drive two distinct motions,” adds co-author Wan-Ru Li.
According to the researchers, this is presumably the first recorded observation of such a phenomenon and can have key clinical implications. For instance, understanding how facial movements correlate with internal states can lead to improved diagnostic and treatment strategies for mental health conditions which often involve atypical emotional responses and facial expressions.
Moreover, this newfound knowledge on differential orofacial movements in mice could lead to advancements in understanding animal emotions and help create more compassionate and suitable environments for laboratory animals, pets, and animals in different settings like zoos or farms, ultimately enhancing animal welfare.
We surely hope that this study serves as a milestone for animal welfare, mental health, and neuroscience research.
Neural mechanisms underlying uninstructed orofacial movements during reward-based learning behaviors
Optogenetic stimulation of VTA-DA neurons (oDAS) elicits orofacial movement
Cue-oDAS association induces distinct cue-locked and oDAS-aligned orofacial actions
Accumbal D1Rs mediate oDAS-aligned, but not cue-locked, motion
Different neuronal signals converge in wM1, triggering unique orofacial movements
During reward-based learning tasks, animals make orofacial movements that globally influence brain activity at the timings of reward expectation and acquisition. These orofacial movements are not explicitly instructed and typically appear along with goal-directed behaviors.
Here, we show that reinforcing optogenetic stimulation of dopamine neurons in the ventral tegmental area (oDAS) in mice is sufficient to induce orofacial movements in the whiskers and nose without accompanying goal-directed behaviors.
Pavlovian conditioning with a sensory cue and oDAS elicited cue-locked and oDAS-aligned orofacial movements, which were distinguishable by a machine-learning model. Inhibition or knockout of dopamine D1 receptors in the nucleus accumbens inhibited oDAS-induced motion but spared cue-locked motion, suggesting differential regulation of these two types of orofacial motions.
In contrast, inactivation of the whisker primary motor cortex (wM1) abolished both types of orofacial movements. We found specific neuronal populations in wM1 representing either oDAS-aligned or cue-locked whisker movements. Notably, optogenetic stimulation of wM1 neurons successfully replicated these two types of movements.
Our results thus suggest that accumbal D1-receptor-dependent and -independent neuronal signals converge in the wM1 for facilitating distinct uninstructed orofacial movements during a reward-based learning task.