Credit: Photo courtesy of Steve RamirezWhat inspired you and your research partners to study the impact of fear memories on habits in different environments?The first thing is that with fear memories, its one of the most, if not the most, most studied kind of memory in rodents. Its a 3D phenomenon dispersed throughout the brain however theres cells throughout the brain that are included in the formation of a provided memory such as a fear memory and that theres locations of the brain that are particularly active during the development of a memory.What were the main findings about freezing behavior in smaller sized versus bigger environments during fear memory reactivation?Its luckily simple and science is frequently anything. If we trigger a worry memory, however while an animal is with his rodent pals in the cage, will that alter how that fear memory manifests differently?In that sense, we hope it offers more of a roadmap on what these experiments can look like, and really build off the concept that we can chart and trigger memories out whats occurring throughout the brain in three measurements. We can use that to attempt to continue this scavenger hunt of discovering targets in the brain for mitigating fear responses.In terms of broader ramifications, how could the findings of this research study contribute to our understanding of the relationship between memory, brain function, and behavioral responses in different situations?The greatest take home is that the brain processes a lot of details before a memory is translated into action. I believe that for me, one of the most important points is that an idea– and Im using thought and memory here interchangeably– particularly one connected to a memory, will make us feel all sorts of things associated with that memory.
Neuroscientists at Boston University found that fear memories in rodents lead to different behaviors depending upon the environments size. This study, including optogenetic activation of fear engrams, provides new perspectives on the adaptability of worry reactions and potential treatments for fear-based disorders. Credit: SciTechDaily.com In new research study, Boston University neuroscientist Dr. Steve Ramirez and partners examine the dynamic nature of worry reactions in varied environments and their impacts.In a world coming to grips with the intricacies of psychological health conditions like ptsd, anxiety, and anxiety, new research from Boston University neuroscientist Dr. Steve Ramirez and partners offers a special point of view. The research study, recently published in the Journal of Neuroscience, delves into the intricate relationship between fear memories, brain function, and behavioral reactions. Dr. Ramirez, along with his co-authors Kaitlyn Dorst, Ryan Senne, Anh Diep, Antje de Boer, Rebecca Suthard, Heloise Leblanc, Evan Ruesch, Sara Skelton, Olivia McKissick, and John Bladon, explore the elusive principle of worry engrams, shedding light on the physical symptom of memory in the brain. As Ramirez emphasizes, the effort was led by Dorst and Senne, with the job acting as the cornerstone of Dorsts PhD.Beyond its implications for neuroscience, their research marks significant strides in comprehending memory development and holds guarantee for advancing our comprehension of numerous behavioral responses in different situations, with prospective applications in the realm of mental health. In this Q&A, Dr. Ramirez discusses the motivations, obstacles, and key findings of the study.Dr. Steve Ramirez. Credit: Photo courtesy of Steve RamirezWhat encouraged you and your research partners to study the impact of fear memories on behavior in different environments?The very first thing is that with fear memories, its one of the most, if not the most, most studied type of memory in rodents. Its something that gives us a quantitative, measurable behavioral readout. So when an animals in a fearful state, we can begin looking at how its behavior has altered and mark those modifications in behavior as like an index of worry. Worry memories in particular are our point because they lead to some stereotyped behaviors in animals such as freezing in location, which is one of many methods that fear manifests behaviorally in rodents. Thats one angle. The 2nd angle being that worry is such a core part of a variety of pathological states in the brain. So including probably specifically PTSD, however also including generalized anxiety, for instance, and even particular parts of depression for that matter. Theres a very direct link in between a worry memory and its capability to devolve or develop in a sense into a pathological state such as PTSD. It offers us a window into whats going on in those circumstances. We studied fear due to the fact that we can measure it predictably in rodents, and it has direct translational significance in conditions including dysregulated worry actions as well.Can you discuss what fear engrams are and how you utilized optogenetics to reactivate them in the hippocampus?An engram is this evasive term that typically indicates the physical symptom of memory. So, whatever memorys physical identity remains in the brain, thats what we term an engram. The general architecture in the brain that supports the structure that is memory. I say evasive since we dont actually understand what memory fully appears like in the brain. And we absolutely do not know what an engram looks like. We do have ideas of the iceberg kind of tips that for the previous decade, weve been able to truly utilize a lot of cutting edge tools in neuroscience to study.In our laboratory, weve made a lot of headway in picturing the physical substrates of memories in the brain. For example, we understand that theres cells throughout the brain. Its a 3D phenomenon distributed throughout the brain but theres cells throughout the brain that are associated with the formation of an offered memory such as a fear memory which theres locations of the brain that are particularly active throughout the development of a memory.What were the primary findings about freezing habits in smaller sized versus bigger environments during worry memory reactivation?Its luckily simple and science is typically anything but. If we reactivate this worry memory when the animals are in a little environment, then theyll default to freezing– they stay in location. This is most likely an adaptive reaction so as to prevent detection by a possible hazard. We believe the brain has done the calculus of, can I leave this environment? Possibly not. Let me sit in a corner and be alert and try to spot any potential risks. Hence, the habits manifests as freezing.The cool part is that because same animal, if we reactivate the specific very same cells that resulted in freezing in the small environment, everything is the exact very same: the cells that were triggering, the fear memory that it corresponds to, the works. If we do that in a big environment, then it all goes away. The animals dont freeze anymore. A different collection of behaviors emerge. Essentially, they begin doing other things that is simply not freezing, which was the initial take home for us, was that they, when we reactivate the worry memory up, or synthetically, when we do that in the little environment, they freeze, when we do that in the large environment, they do not freeze.What was cool for us about that finding in particular was that it suggests that these fear memory cells are not hardwired to produce the exact same precise response each and every single time theyre reactivated. At some time, the brain determines, “Im remembering a fear memory and now I need to find out whats the most adaptive response.” Were there any challenges or challenges you came across throughout the research study process, and how did you conquer them?Theres a couple. The first is that the habits, ironically enough, was reasonably simple for us to replicate and to do once again and again and once again– so that we were convinced that there was some component of truth there. In the second half of the study, and the one that most likely takes up the most space in the paper, was determining what in the brain is moderating this distinction. As we observed, the animals are freezing when we synthetically activate a memory in a little environment, and theyre not freezing in the large environment. Were activating the exact same cells. So, what is different about the animals brain state? What is the animals brain state when were reactivating this memory in the little environment compared to the large environment? Clearly its manifesting as totally opposite habits– freezing and lack thereof.So, we desired to discover what in the brain is taking place in those 2 conditions that are various. That led us down a multi-year rabbit hole of trying to map out activity patterns in the entire brain, as an outcome of promoting these memories in these various sized environments. We went through a whole mess of innovations where we took a look at the brain– we can actually make the brain completely transparent– so that we can take elegant microscopic lens and image the brain in 3 dimensions. Think about it as a cellular MRI for rodents. When we stimulate a memory, we produced these brain large maps of whats responsive in the brain. Then we asked ourselves, how does that map of the brain in the small environment compare to the map of the brain when were triggering the memory in the big environment?In short, theres resemblances and theres differences. That theres certain parts of the brain that are always active when we promote a memory, despite the environments that the animals are in. Then theres other parts that are just active in the large environment or just active when we do the experiment in the little environment. Thats cool because that lets us know that those areas that are not in typical in between the 2 may be the ones that are in fact essential in moderating the brains decision to either freeze or to not freeze. This procedure was challenging since it required a lot of technical prowess such as making brains transparent and imaging them in 3 dimensions down at the cellular level.How might the insights from this research study be applied or extended in the future, particularly in the context of understanding and dealing with fear-related disorders?Context clearly matters. One relatable example is that two people may be experiencing the same level of anxiety, however the underlying reason for that stress and anxiety might be hugely different throughout the two individuals. The manner ins which stress and anxiety affects individuals behaviorally might also be very different. Someone may be pacing up and down the space, whereas the other one is just kind of sitting and lost in their own ideas. The very same faculty of cognition can appear two extremely various ways, in how its expressed. In this case, we believe its the very same thing with fear memories– how theyre expressed will depend on what the animal is experiencing. Perhaps in individuals, how a given memory is revealed also is going to depend on the context, like the whos there, the what, where, why, and so on.So thats one angle, however I believe that the more direct significance is that weve understood for a years that these cells in the hippocampus are enough to jumpstart a memory when we reactivate them. However then theres the question of, what occurs if we reactivate them, and we alter more than simply the environment size? If we activate a fear memory, but while an animal is with his rodent buddies in the cage, will that alter how that worry memory manifests differently?In that sense, we hope it offers more of a roadmap on what these experiments can appear like, and truly build off the idea that we can chart and activate memories out whats happening throughout the brain in 3 measurements. We can utilize that to try to continue this scavenger hunt of finding targets in the brain for reducing worry responses.In regards to wider implications, how might the findings of this study add to our understanding of the relationship between memory, brain function, and behavioral reactions in different situations?The most significant take home is that the brain processes a lot of info before a memory is translated into action. I think that for me, one of the most crucial points is that an idea– and Im using idea and memory here interchangeably– particularly one linked to a memory, will make us feel all sorts of things connected with that memory. Once again, it could be a positive memory, it might be an unfavorable memory, and whatever in between, however it does not need to appear the same way. I think its an actually crucial point for people to understand, due to the fact that it serves as a pointer that the procedure of turning thought into action differs throughout individuals and what they are experiencing in genuine time.Lets say I was being in front of you right now. I could go through the most euphoric memories that I have and the dimmest darkest memories that I have– go through the entire spectrum of emotion from bliss, gleefulness and happiness to mournful, pensive, or sad, the works. But, I might go through all of that without ever actually batting an eye, and you would never truly understand that those are the thoughts that Im having unless I somehow volunteer that details. The other thing to consider would be, possibly theres subtle things happening beneath the hood here that we might pick up on. Possibly when Im thinking about sad memories I slouch a bit more, my students dilate, or I sweat a little bit more.Whereas when I recall favorable memories, maybe I sort of chipper up a bit, my posture is much better, my students dilate another method, and my heart rate increases. Theres other not so obvious metrics for reading out a memory that I believe can be utilized. Eventually, I hope that this research a minimum of motivates individuals to dive a bit more deeply into whats actually going on and learn how our memories are eventually causing an action. I wish to understand the magic thats occurring, and I hope that the research study assisted unpack a bit of that magic.Originally released on Medium.Reference: “Hippocampal engrams generate variable behavioral responses and brain-wide network states” by Kaitlyn E. Dorst, Ryan A. Senne, Anh H. Diep, Antje R. de Boer, Rebecca L. Suthard, Heloise Leblanc, Evan A. Ruesch, Angela Y. Pyo, Sara Skelton, Lucas C. Carstensen, Samantha Malmberg, Olivia P. McKissick, John H. Bladon and Steve Ramirez, 27 November 2023, Journal of Neuroscience.DOI: 10.1523/ JNEUROSCI.0340-23.2023.