Monday, December 25th, 2017

Time	Event
2:59p	How the brain selectively remembers new places When you enter a room, your brain is bombarded with sensory information. If the room is a place you know well, most of this information is already stored in long-term memory. However, if the room is unfamiliar to you, your brain creates a new memory of it almost immediately. MIT neuroscientists have now discovered how this occurs. A small region of the brainstem, known as the locus coeruleus, is activated in response to novel sensory stimuli, and this activity triggers the release of a flood of dopamine into a certain region of the hippocampus to store a memory of the new location. “We have the remarkable ability to memorize some specific features of an experience in an entirely new environment, and such ability is crucial for our adaptation to the constantly changing world,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and director of the RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory. “This study opens an exciting avenue of research into the circuit mechanism by which behaviorally relevant stimuli are specifically encoded into long-term memory, ensuring that important stimuli are stored preferentially over incidental ones,” adds Tonegawa, the senior author of the study. Akiko Wagatsuma, a former MIT research scientist, is the lead author of the study, which appears in the Proceedings of the National Academy of Sciences the week of Dec. 25. New places In a study published about 15 years ago, Tonegawa’s lab found that a part of the hippocampus called the CA3 is responsible for forming memories of novel environments. They hypothesized that the CA3 receives a signal from another part of the brain when a novel place is encountered, stimulating memory formation. They believed this signal to be carried by chemicals known as neuromodulators, which influence neuronal activity. The CA3 receives neuromodulators from both the locus coeruleus (LC) and a region called the ventral tegmental area (VTA), which is a key part of the brain’s reward circuitry. The researchers decided to focus on the LC because it has been shown to project to the CA3 extensively and to respond to novelty, among many other functions. The LC responds to an array of sensory input, including visual information as well as sound and odor, then sends information on to other brain areas, including the CA3. To uncover the role of LC-CA3 communication, the researchers genetically engineered mice so that they could block the neuronal activity between those regions by shining light on neurons that form the connection. To test the mice’s ability to form new memories, the researchers placed the mice in a large open space that they had never seen before. The next day, they placed them in the same space again. Mice whose LC-CA3 connections were not disrupted spent much less time exploring the space on the second day, because the environment was already familiar to them. However, when the researchers interfered with the LC-CA3 connection during the first exposure to the space, the mice explored the area on the second day just as much as they had on the first. This suggests that they were unable to form a memory of the new environment. The LC appears to exert this effect by releasing the neuromodulator dopamine into the CA3 region, which was surprising because the LC is known to be a major source of norepinephrine to the hippocampus. The researchers believe that this influx of dopamine helps to boost CA3’s ability to strengthen synapses and form a memory of the new location. They found that this mechanism was not required for other types of memory, such as memories of fearful events, but appears to be specific to memory of new environments. The connections between the LC and CA3 are necessary for long-term spatial memories to form in CA3. “The selectivity of successful memory formation has long been a puzzle,” says Richard Morris, a professor of neuroscience at the University of Edinburgh, who was not involved in the research. “This study goes a long way toward identifying the brain mechanisms of this process. Activity in the pathway between the locus coeruleus and CA3 occurs most strongly during novelty, and it seems that activity fixes the representations of everyday experience, helping to register and retain what’s been happening and where we’ve been.” Choosing to remember This mechanism likely evolved as a way to help animals survive, allowing them to remember new environments without wasting brainpower on recording places that are already familiar, the researchers say. “When we are exposed to sensory information, we unconsciously choose what to memorize. For an animal’s survival, certain things are necessary to be remembered, and other things, familiar things, probably can be forgotten,” Wagatsuma says. Still unknown is how the LC recognizes that an environment is new. The researchers hypothesize that some part of the brain is able to compare new environments with stored memories or with expectations of the environment, but more studies are needed to explore how this might happen. “That’s the next big question,” Tonegawa says. “Hopefully new technology will help to resolve that.” The research was funded by the RIKEN Brain Science Institute, the Howard Hughes Medical Institute, and the JPB Foundation. (Comment on this)
3:00p	Cleaner air, longer lives The air we breathe contains particulate matter from a range of natural and human-related sources. Particulate matter is responsible for thousands of premature deaths in the United States each year, but legislation from the U.S. Environmental Protection Agency (EPA) is credited with significantly decreasing this number, as well as the amount of particulate matter in the atmosphere. However, the EPA may not be getting the full credit they deserve: New research from MIT’s Department of Civil and Environmental Engineering (CEE) proposes that the EPA’s legislation may have saved even more lives than initially reported. “In the United States, the number of premature deaths associated with exposure to outdoor particulate matter exceeds the number of car accident fatalities every year. This highlights the vital role that the EPA plays in reducing the exposure of people living in the United States to harmful pollutants,” says Colette Heald, associate professor in CEE and the Department of Earth, Atmospheric and Planetary Sciences. The EPA’s 1970 Clean Air Act and amendments in 1990 address the health effects of particulate matter, specifically by regulating emissions of air pollutants and promoting research into cleaner alternatives. In 2011 the EPA announced that the legislation was responsible for a considerable decrease in particulate matter in the atmosphere, estimating that over 100,000 lives were saved every year from 2000 to 2010. However, the report did not consider organic aerosol, a major component of atmospheric particulate matter, to be a large contributor to the decline in particulate matter during this period. Organic aerosol is emitted directly from fossil fuel combustion (e.g. vehicles), residential burning, and wildfires but is also chemically produced in the atmosphere from the oxidation of both natural and anthropogenically emitted hydrocarbons. The CEE research team, including Heald; Jesse Kroll, an associate professor of CEE and of chemical engineering; David Ridley, a research scientist in CEE; and Kelsey Ridley SM ’15, looked at surface measurements of organic aerosol from across the United States from 1990 to 2012, creating a comprehensive picture of organic aerosol in the United States. “Widespread monitoring of air pollutant concentrations across the United States enables us to verify changes in air quality over time in response to regulations. Previous work has focused on the decline in particulate matter associated with efforts to reduce acid rain in the United States. But to date, no one had really explored the long-term trend in organic aerosol,” Heald says.  The MIT researchers found a more dramatic decline in organic aerosol across the U.S. than previously reported, which may account for more lives saved than the EPA anticipated. Their work showed that these changes are likely due to anthropogenic, or human, behaviors. The paper is published this week in Proceedings of the National Academy of Sciences. “The EPA report showed a very large impact from the decline in particulate matter, but we were surprised to see a very little change in the organic aerosol concentration in their estimates,” explains Ridley. “The observations suggest that the decrease in organic aerosol had been six times larger than estimated between 2000 and 2010 in the EPA report.” Using data from the Interagency Monitoring of Protected Visual Environments (IMPROVE) network the researchers found that organic aerosol decreased across the entire country in the winter and summer seasons. This decline in organic aerosol is surprising, especially when considering the increase in wildfires. But the researchers found that despite the wildfires, organic aerosols continue to decline.  The researchers also used information from the NASA Modern-Era Retrospective analysis for Research and Applications to analyze the impact of other natural influences on organic aerosol, such as precipitation and temperature, finding that the decline would be occurring despite cloud cover, rain, and temperature changes.  The absence of a clear natural cause for the decline in organic aerosol suggests the decline was the result of anthropogenic causes. Further, the decline in organic aerosol was similar to the decrease in other measured atmospheric pollutants, such as nitrogen dioxide and carbon monoxide, which are likewise thought to be due to EPA regulations. Also, similarities in trends across both urban and rural areas suggest that the declines may also be the result of behavioral changes stemming from EPA regulations. By leveraging the emissions data of organic aerosol and its precursors, from both natural and anthropogenic sources, the researchers simulated organic aerosol concentrations from 1990 to 2012 in a model. They found that more than half of the decline in organic aerosol is accounted for by changes in human emissions behaviors, including vehicle emissions and residential and commercial fuel burning.  “We see that the model captures much of the observed trend of organic aerosol across the U.S., and we can explain a lot of that purely through changes in anthropogenic emissions. The changes in organic aerosol emissions are likely to be indirectly driven by controls by the EPA on different species, like black carbon from fuel burning and nitrogen dioxide from vehicles,” says Ridley. ”This wasn’t really something that the EPA was anticipating, so it’s an added benefit of the Clean Air Act.” In considering mortality rates and the impact of organic aerosol over time, the researchers used a previously established method that relates exposure to particulate matter to increased risk of mortality through different diseases such as cardiovascular disease or respiratory disease. The researchers could thus figure out the change in mortality rate based on the change in particulate matter. Since the researchers knew how much organic aerosol is in the particulate matter samples, they were able to determine how much changes in organic aerosol levels decreased mortality. “There are costs and benefits to implementing regulations such as those in the Clean Air Act, but it seems that we are reaping even greater benefits from the reduced mortality associated with particulate matter because of the change in organic aerosol,” Ridley says. “There are health benefits to reducing organic aerosol further, especially in urban locations. As we do, natural sources will contribute a larger fraction, so we need to understand how they will vary into the future too.” This research was funded, in part, by the National Science Foundation, the National Aeronautics and Space Administration, and the National Oceanic and Atmospheric Administration. (Comment on this)

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