Scientists use zebrafish to understand how the brain makes decisions!

Dr. Hannah Shoenhard was the lead author on this study. Hannah hopes to one day run a lab that connects the “small picture“ (molecules, genes, and proteins) to the “big picture“ (circuits and behaviors) in neuroscience. After earning her PhD in the Granato lab using zebrafish as a model system to study decision making, she moved to do a postdoc in the Sehgal lab studying sleep and memory in fruit flies.

or technically,

The calcium-sensing receptor (CaSR) regulates zebrafish sensorimotor decision making via a genetically defined cluster of hindbrain neurons

[See Original Abstract on Pubmed]

Authors of the study: Hannah Shoenhard, Roshan A. Jain, Michael Granato

How we make decisions is a question that scientists and philosophers have considered for ages. But did you know that there are different types of decision making? The type that we are most familiar with involves decisions that we make in our everyday lives: Should I walk to school or take the bus? Should I have pasta or salad for dinner? But the brain is actually responsible for lots of different kinds of decisions - some of which we don’t even think about! One type of decision making that is commonly studied in the field of neuroscience is called sensorimotor decision making. In this form of decision making, the brain takes in sensory information from the world, processes the information while considering past experiences, and then produces a behavioral response. 

Figure 1:

Image of a zebrafish used in scientific research. 

Source: https://news.mit.edu/2022/smarter-zebrafish-study-1118

To understand more about this type of decision making, Dr. Hannah Shoenhard, a recent Penn Neuroscience PhD graduate, and her lab used zebrafish, a common animal model that is used in neuroscience research. Her lab had previously found that when fish are presented with a sudden quiet sound, they respond with a “reorientation” response - the fish slowly turn their bodies. But if the fish are presented with a sudden loud sound, they respond with an “escape” response - the fish rapidly turn their bodies. Having learned about this fascinating behavioral phenomenon, Hannah was interested in how different proteins may be involved in this sensorimotor decision making process. Through whole-genome sequencing (a fancy way of scanning for important genes) in the zebrafish, the lab identified a protein named CaSR that is essential for sensorimotor decision. When the lab removed CaSR from the zebrafish, they found that they would produce the wrong response to a loud sound by reorienting instead of trying to escape.

Given that CaSR is important for normal sensorimotor decision making, Hannah next wanted to know which part of the zebrafish brain uses CaSR to perform this behavior. She first looked at the neurons that drive the escape response. When she reintroduced CaSR into these escape neurons, she found that it did not restore the correct escaping response. This meant that CaSR had to be acting elsewhere.

To find the location where CaSR is acting, Hannah developed a novel experimental strategy. This approach combined behavior and brain imaging. Hannah expressed CaSR in random sets of neurons in zebrafish that didn’t have any CaSR of their own. Some of these fish displayed normal decision-making, meaning CaSR had been expressed in the “correct” neurons, and some displayed impaired decision-making, meaning the “correct” neurons had been missed. Hannah then compared which neurons had CaSR in zebrafish that displayed normal decision-making or abnormal decision-making. Using this novel strategy, Hannah found a brain region in the zebrafish called DCR6, which is located in the hindbrain, near both the escape and reorientation neurons. The hindbrain controls many reflexive behaviors in both fish and humans. To validate her findings and test if this region is actually involved in sensorimotor decision making, she drove extra CaSR expression in the DCR6 and found that this was sufficient to drive escape responses in zebrafish exposed to quiet noises – in other words, the opposite of what happens when CaSR is missing.  Additionally, she used the original zebrafish strain that lacked CaSR and specifically restored CaSR only in DCR6 neurons. Hannah found that these fish performed reorientations in response to quiet sounds and escapes in response to loud sounds - just as we expect healthy zebrafish to do! 

Thus far, Hannah’s experiments have pointed to two major findings: 1) CaSR is important for normal sensorimotor decision making and 2) CaSR acts locally in DCR6 neurons, but not reorientation or escape neurons, to enable normal sensorimotor decision making. Given these findings, Hannah asked an important follow-up question - are there connections between DCR6 and reorientation or escape neurons? To answer this, she used a unique zebrafish strain that labels DCR6 neurons and escape neurons. Hannah found that DCR6 neurons do connect to escape neurons but found no connections with reorientation neurons. Nevertheless, Hannah and her colleagues were excited to find this result. 

Hannah’s amazing work in the zebrafish underscores that it is important to examine the brain both at a large scale (i.e., behavior and decision making) as well as a small scale (i.e., individual neurons and proteins, like CaSR) in order to more fully understand how it works. Secondly, her work tells us that decisions are the result of distinct parts of the brain working together to perform a behavior. When you decide to have a salad for dinner, there is one part of your brain that controls your muscles and allows you to eat the salad. There is a different part of your brain that helps in deciding to eat the salad in the first place! In the example of the zebrafish, reorientation/escape neurons allow the fish to perform the actions, but the decision making site is elsewhere - namely, in a brain region known as DCR6. On a final note, Hannah’s research reminds us of the incredible value and insight that animal models, like the zebrafish, bring to us. They allow us to study behaviors that are very seemingly very human (like decision making) in very deliberate and precise ways!

About the brief writer: Jafar Bhatti

Jafar is a PhD Candidate in Maria Geffen’s lab. He is broadly interested in brain networks involved in auditory processing and decision-making.

Want to learn more about how these researchers study decision making in zebrafish? You can find Hannah’s paper here!

I can almost see it now: How having a more vivid visual imagination makes us less willing to wait.

or technically,

The Vivid Present: Visualization Abilities Are Associated with Steep Discounting of Future Rewards.

[See Original Abstract on Pubmed]

Authors of the study: Trishala Parthasarathi, Mairead H. McConnell, Jeffrey Luery, Joseph W. Kable

Most of us struggle to make better life choices. We may be trying to lose weight, but those cookies look delicious. We probably should get a good night’s rest, but Netflix is already loading the next episode of our favorite show. In each of these situations we have to decide between two different types of rewards: one that is instantly gratifying but may not improve our life in the long run, and one that won’t pay off immediately but could ultimately be more satisfying. Often we end up choosing the short-term and potentially less rewarding option. How do people make these decisions? Is there something we can do to make it easier to wait for a reward?

To answer these questions, researchers have started to investigate what things make people choose short-term or long-term rewards. The primary result found by these studies is that people are more willing to wait for future rewards when they are instructed to imagine the future before making their choice. Researchers have suggested that imagining the future makes long-term rewards seem more attainable or less far away in time, so people are more willing to wait for them. Given this hypothesis, Trish Parthasarathi, a graduate student in Dr. Joe Kable’s lab, made two predictions. First, she predicted that people who had more vivid visual imaginations, and therefore could more easily imagine the future, would be more willing to wait for future rewards. Second, she predicted that training people to improve their visual imaginations, and thus making it easier to imagine the future, would also make them more willing to wait for future rewards. Testing this second prediction was very important as it would establish whether people who happened to have more vivid visual imaginations just happened to be more willing to wait for rewards (that is, that the two are correlated) or if people were more willing to wait for rewards because they had a more vivid visual imagination (that is, one causes the other).

Trish designed a study to test her two predictions. At the beginning of the study, she used a well-established questionnaire to measure the vividness of each participant’s imagination. Then, to evaluate how patient they were at waiting for future rewards, Trish had each participant do a task in which they were repeatedly asked to choose between a smaller monetary reward that they would receive immediately and a larger reward that they would receive later. The immediate rewards ranged between $10 and $34. The delayed rewards were either $25, $30, or $35 and were always larger than the immediate reward. The wait time ranged from one day to 6 months. For example, one choice might be whether to receive $11 immediately, or $30 in 24 days.

After participants had performed this task once to assess their patience for reward, they were randomly assigned to either a control relaxation training or visual imagination training group. In both groups, participants were led through mindfulness meditations. In these meditations, individuals are asked to bring awareness to their bodies, breathing, and the physical sensations they are currently experiencing and to use this awareness to help them relax in the present moment. In the imagination training group, participants were also asked to focus on a goal that they would like to achieve in the future. Specifically, they were led through two vivid scenarios in which they could imagine overcoming potential obstacles and experience the feelings of achieving their goal. Thus, the main difference between the two groups is that the control group was asked to think about the present only while the training group was specifically asked to think about the future. After 4 weeks of training, all participants redid the questionnaire to see if their visual imagination had improved and redid the decision task to see what effect the training had on their ability to wait for rewards.

Trish and her colleagues predicted three results from these experiments. First, they predicted that people who had more vivid imaginations would be more likely to choose the larger, later rewards in the task. Next, they predicted that the participants who went through the visual imagination training would have more vivid imaginations. Finally, they predicted that those individuals who had improved the vividness of their imaginations would be more likely to choose the larger later reward than before they had completed the training.

Surprisingly, Trish’s findings were the exact opposite of two of these predictions! She observed that people who had more vivid visual imaginations were actually less likely to choose to wait for the larger, later reward in the task. She also found that while the visualization training program did successfully improve participants' visual imagination compared to the control relaxation training group, these individuals became more impatient: they were now less likely than they were before training to choose to wait for the later reward in the task.

Trish and her colleagues offered a couple of possible explanations for why they observed these unexpected results. One explanation is that the visual imagination training actually ended up making future results seem as though they were further away or had already been achieved, thus pushing people towards focusing on the present. In other words: people might imagine the obstacles so clearly that they wouldn’t want to face them, or they might imagine the reward so vividly that they felt that it was already achieved. Either of these imagined scenarios could lead them to refocus on the present reality instead of the future reward. The other explanation Trish and her colleagues proposed is that we can use our imagination to imagine the present or the future, but the present is often already more vivid and easily imagined. Thus, when people were trained to visualize more effectively, the present actually became even easier to imagine and thus people were biased towards the present. Finally, they also noted that although we often think of being less patient as a bad thing, there are times when choosing the more immediate option may be beneficial. Always waiting for the perfect option can cause us to be indecisive and miss out on certain opportunities. This visualization training could be beneficial for helping people overcome indecision, but another study would have to be done to see if this is true.

There are two important points to take away from this study. First, this study demonstrates that unfortunately, sometimes the strategies that seem to make a lot of sense for improving our behavior don’t actually work. Fortunately, we can design scientific studies to test these strategies and make sure we aren’t following bad advice. Second, next time you are trying to stop yourself from grabbing some cookies or watching another hour of your show, trying to more vividly imagine how you would feel if you made each choice may not be the best way to go!

About the brief writer: Ron DiTullio

Ron is a PhD Candidate in the Cohen Lab and Balasubramanian Group whose work revolves around determining how the brain processes and stores information about the external world. Specifically, he focuses on how we are able to hear and recognize sounds as well as how we remember directions and events of our life.

To learn more about this exciting work, check out Trish’s full paper here.