Something in the Way Mice Lick: Revealing the Secrets of Brain Reward Circuits

What is it about?

This research delves into how a specific type of brain cell – the D2 neuron, named for a particular docking station (receptor) for the “feel-good” neurotransmitter dopamine – controls both our sense of reward and how we physically eat. These neurons are located in the brain's nucleus accumbens, a region known to be a central player in pleasure and motivation. We used a cutting-edge technique called optogenetics, which allows us to use light to precisely turn these genetically modified neurons on or off. We looked at the effect of this on-off switch on the mice: their interest in sugar water, their licking patterns, and their choices about where to hang out when tasty food was an option. We discovered something surprising about D2 neurons in the nucleus accumbens: these cells have a kind of “Jekyll and Hyde” personality. When we stimulated these neurons very rapidly (like flashing a light on and off 20 times a second), the mice seemed to enjoy it – they would actively work to get that stimulation. Think of it like a reward signal. But strangely, that same rapid stimulation also made it harder for them to lick, which meant they drank less sugar water and did not seem to want it as much. It was as if the “reward” button also interfered with their ability to enjoy a treat. However, when we slowed down the stimulation, matching the natural rhythm of their licking (about 8 times a second), they were able to drink more of the sugar water. The interference was much less. And here is the flip side: turning off these D2 neurons led to slightly unpleasant feeling for the mice. They generally avoided situations where these cells were switched off. But – and this is important – they would overcome that avoidance if there was a really delicious, high-fat food available. It is like the ultimate comfort food could override their discomfort.

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Photo by Elena Leya on Unsplash

Photo by Elena Leya on Unsplash

Why is it important?

Decades ago, a lucky accident led James Olds to discover what seemed a simple “pleasure center” in the brain. But we've learned a lot since then. Reward processing is incredibly complex, involving a whole network of brain areas and a variety of interacting cells. Our research adds another layer to this complexity, showing that the same brain cells can play a role in both wanting a reward and being able to get it. Critically, the animal's own actions – their sense of control – and the precise timing of brain cell activity dramatically change the behavioral outcome. These discoveries are important for understanding conditions like addiction, eating disorders, and schizophrenia, where these reward circuits might be going awry. They also emphasize how crucial it is to consider the brain natural rhythms when studying how we experience pleasure and motivation.

Perspectives

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Our research contributes to understanding how the brain processes rewards, challenging some long-held assumptions. We focused on D2 neurons, brain cells previously thought to be mainly involved in avoiding unpleasant experiences. Surprisingly, we found that these neurons can actually be rewarding, especially when the mice controlled the timing of the stimulation themselves. Think of it like this: sometimes you enjoy a song more when you choose to play it, rather than having it forced on you. While our high-tech approach (using light to control these neurons) is powerful, it is not a perfect imitation of what happens naturally in the brain. This highlights the need for future studies that look at how real-world actions and behaviors are intertwined with these reward signals. One of the most intriguing findings is that activating these D2 neurons can be both rewarding and make it harder for the mice to lick. This suggests that, sometimes, the brain might prioritize the motivation to get a reward over actually enjoying it in the moment. It is like being so excited to get a gift that you momentarily forget to appreciate the unwrapping process. This complexity shows that what D2 neurons do depend heavily on how they are activated. This is a big deal for future research and could even lead to new treatments for conditions related to motivation and reward. Our work raises some fascinating new questions: How do these D2 neurons work together with other brain cells (like D1 neurons) in real-time? What other parts of the brain are responsible for the difficulty in licking? And, importantly, how do these findings in mice apply to human behavior and conditions like addiction or eating disorders? But more relevant than new questions, we show that how the stimulation is given matters. By matching the brain stimulation to the mice natural licking rhythm, we could amplify the rewarding effect of the D2 neurons, leading the mice to drink more sugar water. A key takeaway from our work, especially for other scientists using similar techniques, is the importance of timing: syncing brain stimulation with natural biological rhythms, like a mouse's licking, can give us a much clearer picture of how the brain really works, instead of applying artificial stimulation patterns.

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