reposted from https://www.frontiersin.org/articles/10.3389/fneur.2018.00068/full  and it suggests how important circadian rhythms are for life.....

EDITORIAL ARTICLE

Front. Neurol., 16 February 2018 | https://doi.org/10.3389/fneur.2018.00068

Editorial: Intrinsic Clocks

Timo Partonen1* and Daniela D. Pollak2

• 1Department of Public Health Solutions, National Institute for Health and Welfare (THL), Helsinki, Finland
• 2Department of Neurophysiology and Neuropharmacology, Medical University of Vienna, Vienna, Austria

Editorial on the Research Topic

Intrinsic Clocks

The existence of living organisms on our planet has been dependent on and co-evolved with the foreseeable variations in environmental conditions oscillating over recurring periods. All species have responded to these exogenous rhythms by developing endogenous clocks that allow for an approximate, but reliable estimation of the periodic changes and elicit corresponding adaptive processes.

The importance of these mechanisms for health and disease has been highlighted by the 2017 award of the Nobel Prize in Physiology or Medicine to Jeffrey C. Hall, Michael Rosbash, and Michael W. Young for their discoveries of the genetic control of the daily biological rhythm. They explained in molecular terms how the gene named as period contributed to the emergence (eclosion from the pupal case) rhythm of a population and to the locomotor activity of individual flies (Drosophila melanogaster). The key to the explanation was the discovery of transcription-translation feedback loops of the so-called “clock genes.”

This research topic on Intrinsic Clocks which appeared earlier comprises a well-balanced collection of original research and review articles on endogenous rhythms from seasonal and monthly to daily and hourly oscillations in different experimental model systems with analytical approaches from systemic to cellular and molecular levels.

Serchov and Heumann in their review focus on the role of Ras, an enzyme which hydrolyzes guanosine triphosphate and dependent intracellular signaling cascades in the regulation of the circadian rhythm in mice. They elegantly summarize how Ras activity forms a molecular bridge between entrainment of the suprachiasmatic nucleus that is the master clock in the brain and synaptic plasticity in dependent brain regions, such as the hippocampus, and corresponding functions. The extensive study by Chiang et al. specifically investigated rhythmic alterations in the murine hippocampus. They characterized the protein phosphorylation using a mass spectrometry approach with which they provided large-scale quantitative analysis of the daily oscillation of hippocampal phosphorylation events over a range of biological pathways. The hippocampus is a key focus also in the review by Urs Albrecht. It features the role of circadian proteins in the control of adult hippocampal neurogenesis, reciprocally implicated in depression and antidepressant responses. He discusses neurobiological mechanisms implicated in the pathogenesis of mood disorders, such as monoaminergic neurotransmission and stress response by the hypothalamic–pituitary–adrenal axis. The hypothalamus and the pituitary are further involved in seasonal cycles as highlighted in the review by Lewis and Ebling who elaborate in detail on the role of tanycytes, pituitary radial glial cells, in the regulation of circannual clocks in hamsters. They provide evidence supporting their hypothesis that tanycytes serve as central organizers of seasonal rhythms in the adult hypothalamus. Raible et al. present in their review on marine animals the current insight in the cellular mechanisms in molecular detail the monthly or semi-monthly rhythms. They express their worry about light pollution and further review the relevance of circalunar rhythms to mammalian physiology and reproduction in specific. They speculate that these rhythms may be the remnant of evolutionary ancient clocks, which were uncoupled from a natural entrainment mechanism.

Bourguignon and Storch summarize recent findings of the cellular substrate and mechanism, which generate locomotor activity with periods of 2–6 h. Such rhythms are normally integrated with circadian rhythms, but often lack the period stability and expression robustness. They further review the concept of the dopaminergic ultradian oscillator and show that ultradian locomotor rhythms rely on cells in the brain using dopamine for transmission. Intriguingly, Monje et al. report in their study on interleukin-6 knockout mice that the ultradian locomotor rhythm was impaired under both light-entrained and free-running conditions, whereas the circadian period and the level of locomotor activity as well as the phase shift response to light exposure at night remained normal. During the day, Cry1 and Bhlhe41 expression levels were increased whereas those of Nr1d2 were decreased in the hippocampus. Liu and Zhang first created mutants of cryptochrome circadian clock 1 (Cry1) protein at potential phosphorylation sites and conducted thereafter a screen in Cry1/Cry2 double deficient cells. They targeted at identifying mutations that disrupted circadian rhythms. They found that these single amino acid substitutions changed not only the circadian period, but also repression activity, protein stability, or cellular localization of the protein. Concerning the circadian period, Narasimamurthy and Virshup elucidate in their review the molecular mechanisms that regulate an enigma of the clock. Unlike other chemical reactions, the output of the clock as measured with the period remains nearly constant with fluctuations in ambient temperature. This is called as temperature compensation. The key lies especially in the mechanism that controls the stability of period circadian clock 2 protein. Clock-enhancing small molecules have become of particular interest as candidate chronotherapeutics, since there is a close association of circadian amplitude dampening with progression of chronic diseases, especially that of mood disorders. Gloston et al. present in their review an update of the regulatory mechanisms of circadian amplitude and the current status of these small molecules of therapeutic interest. Millius and Ueda introduce the readers to study of biology which takes advantage of engineering and mathematical tools to model and test the behaviors of the intrinsic clocks. It has evolved through the development of both wet lab and in silico work. The goal here is to understand the clocks that are made up of a range of complex properties of cells, tissues, and organisms.

The cross-section of studies comprised in this research topic on Intrinsic Clocks highlights the vibrant scientific activity in the field of the investigation of endogenous biological rhythms and their relevance for physiology and pathology.

Author Contributions

TP and DP planned and wrote the manuscript together.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Keywords: circadian rhythm, depression, marine biology, mouse model, plasticity, seasonality, small-molecule, systems biology

Citation: Partonen T and Pollak DD (2018) Editorial: Intrinsic Clocks. Front. Neurol. 9:68. doi: 10.3389/fneur.2018.00068

Received: 04 December 2017; Accepted: 29 January 2018;
Published: 16 February 2018

Edited and Reviewed by: Yves A. Dauvilliers, Hôpital Gui De Chauliac, France

Copyright: © 2018 Partonen and Pollak. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Timo Partonen, timo.partonen@thl.fi

reposted from

How Experience Shapes Adult Neurogenesis

Interneurons and mature granule cells in the adult mouse brain are critical for newborn neurons’ responses to novel environments.

By Ruth Williams | October 27, 2016

Granule neurons in the mouse dentate gyrusWIKIMEDIA, AVILA, J.Newly made cells in the brains of mice adopt a more complex morphology and connectivity when the animals encounter an unusual environment than if their experiences are run-of-the-mill. Researchers have now figured out just how that happens. According to a study published today (October 27) in Science, a particular type of cell—called an interneuron—in the hippocampus processes the animals’ experiences and subsequently shapes the newly formed neurons.

“We knew that experience shapes the maturation of these new neurons, but what this paper does is it lays out the entire circuit through which that happens,” said Heather Cameron, a neuroscientist at the National Institute of Mental Health in Bethesda who was not involved with the work. “It’s a really nicely done piece of work because they go step-by-step and show all of the cells that are involved and how they’re connected.”

Most of the cells in the adult mammalian brain are mature and don’t divide, but in a few regions, including an area of the hippocampus called the dentate gyrus, neurogenesis occurs. The dentate gyrus is thought to be involved in the formation of new memories. In mice, for instance, exploring novel surroundings electrically activates the dentate gyrus and can affect the production, maturation, and survival of the newly born cells. Now, Alejandro Schinder and his team at the Leloir Institute in Buenos Aires, Argentina, have investigated the process in detail.

Newborn dentate gyrus neurons, which are called granule cells, take six weeks to fully develop and integrate into the mouse brain’s existing neural networks, said Schinder. To examine these cells’ development, the team labeled newborn granule cells with red fluorescent protein in the brains of mice and then either left the animals in their regular cages (controls) or exposed them to enriched environments—cages with tunnels and other unusual objects—for different 48 hour periods. Three weeks after the new cells were labeled, the team examined their morphology and activity.

The researchers found that in animals who had been exposed to the enriched environment during a particular period (9 to 11 days after labeling), the young granule cells had longer dendrites with evidence of increased connections with other neurons. Specifically, these cells had a greater number of dendritic spines, the sites of incoming synapses, and more detectable electrical inputs.

Granule cells receive different inputs from surrounding neurons at different stages of their development, Schinder said, which may explain why they are apparently receptive to experiential input only within a short period (day 9 to 11), rather than throughout their development.

The team went on to analyze these neuronal inputs more closely. Through a series of optogenetic and chemogenetic experiments, the researchers showed that mature granule cells activated their younger counterparts via intermediary cells called interneurons. Artificially stimulating either the mature granule cells or the interneurons could recapitulate the effects of environmental enrichment on the young granule cells. Moreover, the team showed that blocking the activity of the interneurons during the animals’ exposure to enriched environments prevented the expected experience-induced morphology in the young granule cells.

“The take home message is that experience can change how these young cells are incorporating into the brain and how they are contributing to brain circuitry,” said Hongjun Song, who studies neurogenesis at the Johns Hopkins University School of Medicine in Baltimore and who did not participate in the research. But, he asked, “what’s the functional impact? Does this process make the mice better learners? Or if you block the process, do they get worse [at learning]?”

As yet, those questions remain unanswered.

D. D. Alvarez et al., “A disynaptic feedback network activated by experience promotes the integration of new granule cells,” Science, 354:459-65, 2016.

Tags

neuroscience, neurogenesis, learning, hippocampus and behavior

Demystifying the Brain’s GPS

I got lost last week coming out of the subway at a new location near York Central Mall north of finch.


this helps me make sense of why I got lost but does not help me find my direction yet!

reposted from the Scientist

Demystifying the Brain’s GPS

Studies in rodents are beginning to reveal how mammalian navigational sense works.

By Tanya Lewis | July 12, 2016

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Superficial (red) and deep (cyan) neurons in CA1 mouse hippocampusNATHAN DANIELSON/MORTIMER B. ZUCKERMAN MIND BRAIN BEHAVIOR INSTITUTEIf you’ve ever found yourself walking a few city blocks only to realize you’ve gone in completely the wrong direction, you’ll appreciate the importance of the brain’s ability to keep track of its location and navigate effectively.

In recent years, research on mammalian navigation has focused on the role of the hippocampus, a banana-shaped structure known to be integral to episodic memory and spatial information processing. The hippocampus’s primary output, a region called CA1, is known to be divided into superficial and deep layers. Now, using two-photon imaging in mice, researchers at Columbia University in New York have found these layers have distinct functions: superficial-layer neurons encode more-stable maps, whereas deep-layer brain cells better represent goal-oriented navigation, according to a study published last week (July 7) in Neuron.

“There are lots of catalogued differences in sublayers of pyramidal cells” within the hippocampus, study coauthor Nathan Danielson of Columbia told The Scientist. “The question is, are the principle cells in each subregion doing the same thing? Or is there a finer level of granularity?”

For that past few decades, scientists have been chipping away at an explanation of the brain’s “inner GPS.” The 2014 Nobel Prize in Physiology or Medicine honored the discovery of so-called place cells andgrid cells in the hippocampus, which keep track of an individual’s location and coordinates in space, respectively. Since then, studies have revealed that neurons in different hippocampal regions have distinct genetic, anatomical, and physiological properties, said Attila Losonczy of Columbia, Danielson’s graduate advisor and a coauthor on the study.

“What was unknown was how these subpopulations of pyramidal cells relate to the functions the hippocampus supports,” namely, spatial navigation and memory formation, Losonczy told The Scientist.

Losonczy, Danielson, and colleagues used two-photon calcium imaging to measure neural activity in the superficial and deep sublayers of hippocampal area CA1 in mice while the animals performed either “random foraging” or “goal-oriented learning” tasks. Two-photon imaging “is an extremely powerful method, because it allows us and others to look at the activity of not just a single cell, but of a relatively large population of neurons in hippocampal CA1,” Danielson explained. 

The random foraging task involved running on a treadmill and receiving random water rewards. The goal-oriented learning task had the animals running on a treadmill and receiving rewards at predictable intervals. By measuring when the mice made licking motions while running, the researchers could see whether the animals had learned the location of the rewards.

Deep CA1 neurons were more active than superficial ones in both tasks. Superficial brain cells formed a more stable representation than deep cells of the animals’ environment. But the latter were more highly tuned than the former during the goal-oriented learning task; activity in deep brain cells was also more predictive of the animals’ performance, the researchers found.

“What’s particularly impressive to me in the study is that the anatomy in the hippocampus segregates two aspects of memory”—a stable map of the environment, and a representation of new goals or targets, neuroscientist Howard Eichenbaum of Boston University, who was not involved in the work, told The Scientist.

It’s a bit like Google Maps on your phone, Eichenbaum explained: the plot of your environment with a dot for your location is the stable map, whereas the target address and directions for getting there comprise the goal-oriented system.

The findings support those of previous studies. In a 2011 experiment, neuroscientist Gyorgy Buzsaki of New York University School of Medicine and colleagues found clear functional differences between deep and superficial neurons in the CA1 of rats. “The most astonishing [finding] was that neurons in both layers lock to the theta cycle, the most prominent navigation rhythm in the hippocampus,” Buzsaki toldThe Scientist. But during rapid eye movement (REM) sleep, the deep neurons shifted the phase of their firing by 180 degrees. The findings suggest that, compared with superficial brain cells, deep neurons receive more input from the animal’s external environment, such as when the rodent is seeking a specific goal, Buzsaki noted.

Of course, rodent brains aren’t the same as humans’.

Compared with rodents, humans have a much larger CA1 area, and a much larger ratio of cortex association areas to hippocampus. Extending the findings to humans and other primates “would require a systematic study comparing their [hippocampus] anatomy and structure with their performance” in a navigation task, Danielson said.

Perhaps one of the best studies of human navigation ability is the 2006 London taxi driver study. Researchers from University College London conducted structural MRI scans of London cab drivers and bus drivers, controlling for individuals’ driving experience and stress levels. Compared with the bus drivers, the cab drivers had a higher volume of grey matter in their mid-posterior hippocampi, and a lower volume in their anterior hippocampi. The more years of experience the cabbies had, the greater the grey matter differences, the researchers found.

But interestingly, the taxi drivers were worse than the bus drivers at acquiring new spatial information, suggesting that the former’s expert knowledge of the city “might come at a cost to new spatial memories and gray matter volume in the anterior hippocampus,” the researchers wrote in their study.

“What’s emerging in the field in general are efforts to figure out . . . the dimensions in the hippocampus to map location,” Eichenbaum said. For example, there’s the distinction between stable versus specific knowledge. “We’re constantly going back and forth between general knowledge and specific memories.”

N. Danielson et al., “Sublayer-specific coding dynamics during spatial navigation and learning in hippocampal area CA1,” Neuron, doi:10.1016/j.neuron.2016.06.020, 2016.

E.A. Maguire et al, “London taxi drivers and bus drivers: a structural MRI and neuropsychological analysis,” Hippocampus, doi:10.1002/hipo.20233, 2006.

K. Mizuseki et al., “Hippocampal CA1 pyramidal cells form functionally distinct sublayers,”Nature Neuroscience, doi:10.1038/nn.2894, 2011.

reposted from Harvard Business review

Mindfulness Can Literally Change Your Brain

• Christina Congleton 
• Britta K. Hölzel 
• Sara W. Lazar

JANUARY 08, 2015

The business world is abuzz with mindfulness. But perhaps you haven’t heard that the hype is backed by hard science. Recent research provides strong evidence that practicing non-judgmental, present-moment awareness (a.k.a. mindfulness) changes the brain, and it does so in ways that anyone working in today’s complex business environment, and certainly every leader, should know about.

We contributed to this research in 2011 with a study on participants who completed an eight-week mindfulness program. We observed significant increases in the density of their gray matter. In the years since, other neuroscience laboratories from around the world have also investigated ways in which meditation, one key way to practice mindfulness, changes the brain. This year, a team of scientists from the University of British Columbia and the Chemnitz University of Technology were able to pool data from more than 20 studies to determine which areas of the brain are consistently affected. They identified at least eight different regions. Here we will focus on two that we believe to be of particular interest to business professionals.

The first is the anterior cingulate cortex (ACC), a structure located deep inside the forehead, behind the brain’s frontal lobe. The ACC is associated with self-regulation, meaning the ability to purposefully direct attention and behavior, suppress inappropriate knee-jerk responses, and switch strategies flexibly. People with damage to the ACC show impulsivity and unchecked aggression, and those with impaired connections between this and other brain regions perform poorly on tests of mental flexibility: they hold onto ineffective problem-solving strategies rather than adapting their behavior. Meditators, on the other hand, demonstrate superior performance on tests of self-regulation, resisting distractions and making correct answers more often than non-meditators. They also show more activity in the ACC than non-meditators. In addition to self-regulation, the ACC isassociated with learning from past experience to support optimal decision-making. Scientists point out that the ACC may be particularly important in the face of uncertain and fast-changing conditions.

(Source: Tang et al.)

(Source: Fox et al.)

The second brain region we want to highlight is the hippocampus, a region that showed increased amounts of gray matter in the brains of our 2011 mindfulness program participants. This seahorse-shaped area is buried inside the temple on each side of the brain and is part of the limbic system, a set of inner structures associated with emotion and memory. It is covered in receptors for the stress hormone cortisol, and studies have shown that it can be damaged by chronic stress, contributing to a harmful spiral in the body. Indeed, people with stress-related disorders like depresssion and PTSD tend to have a smaller hippocampus. All of this points to the importance of this brain area in resilience—another key skill in the current high-demand business world.

(Source: Hölzel et al.)

These findings are just the beginning of the story. Neuroscientists have also shown that practicing mindfulness affects brain areas related to perception, body awareness, pain tolerance, emotion regulation, introspection, complex thinking, and sense of self. While more research is needed to document these changes over time and to understand underlying mechanisms, the converging evidence is compelling.

Mindfulness should no longer be considered a “nice-to-have” for executives. It’s a “must-have”:  a way to keep our brains healthy, to support self-regulation and effective decision-making capabilities, and to protect ourselves from toxic stress. It can be integrated into one’s religious or spiritual life, or practiced as a form of secular mental training.  When we take a seat, take a breath, and commit to being mindful, particularly when we gather with others who are doing the same, we have the potential to be changed.

Physical Exercise Beefs Up the Brain

reposted from sfn

also see update comment on this article  and this Science article

Creation Date: 28 Aug 2013 | Review Date: 28 Aug 2013

Physical Exercise Beefs Up the Brain

Source: Society for Neuroscience

Boost your brainpower. Train your brain. These days it's hard not to become distracted by ads for the latest program that promises to help you learn faster and hold onto memories longer.

Run for your life! Regular aerobic exercise has been associated with increased cognitive abilities, including benefits to learning and memory.  But, even as scientists continue to explore the effects of various brain-training programs, a wealth of evidence makes one thing quite clear: physical exercise benefits the brain. Over a decade of research in animals and people shows that engaging in regular aerobic activity leads to changes in the brain associated with improved cognition.

Exercise increases birth of new nerve cells

One of the earliest clues about exercise-induced changes in the brain came in the late 1990s, when a group of scientists decided to compare the brains of mice given unlimited access to an exercise wheel (runners) to those of mice without exercise wheels in their cages (non-runners).

Compared with the non-runners, the researchers discovered that physically fit mice had double the number of new nerve cells in a region of the hippocampus — an area of the brain involved in learning and memory. When the scientists later taught the runners and non-runners to navigate a water maze, they found the runners learned the task faster than the non-runners and took a more direct route to the maze end. 

Fred Gage, a neuroscientist at the Salk Institute for Biological Studies who led both studies, explained that the researchers were "very surprised" to find that the physical activity of a mouse "affects the number of new brain cells and impacts its ability to remember things." At the time, scientists largely agreed the brain affects behavior. Gage's studies suggested the opposite was also true.

Exercising monkeys learn faster

Rodents are avid runners. In fact, with access to the exercise wheel, they will run for hours, racking up several miles each day. Since most people don't put in the hours or mileage running that rodents do, some scientists began to ask: Are long hours of aerobic activity required to see the positive effects of exercise on the brain, or might a more moderate exercise routine do the trick?

To test whether moderate exercise changes the brain, Judy Cameron, a neuroscientist at the University of Pittsburgh, trained a group of middle-aged and older monkeys to run on a treadmill for one hour each day, five days per week for five months — a running regimen similar to that recommended for average, middle-aged adults. As the one group of monkeys ran, a second group of monkeys sat on the treadmills. Over the course of the study the researchers evaluated the monkeys' ability to learn new things.

Regardless of the age of the monkeys, Cameron's group discovered that the monkeys on the running regimen learned new things twice as fast as the sedentary animals.

"We were excited to see that the same moderate level of exercise that is recommended for middle-aged people is able to improve how the brain works in monkeys — increasing alertness, attentiveness, and leading to faster learning," Cameron says.

According to Cameron, it's possible that the cognitive improvements associated with exercise are the result of increased blood flow to the brain. The greater the blood flow, the faster oxygen and other important nutrients can reach nerve cells.

When Cameron's group compared the brains of the monkeys that ran to the brains of sedentary animals they found that the older runners developed more brain blood vessels. However, when the scientists examined the brains of older runners that stopped exercising for three months, they found that the older runners had no more brain blood vessels than their sedentary counterparts.

"These findings suggest that it's important to keep exercising to retain the benefits of exercise," Cameron says.

Brain benefits across lifespan

Studies of animals and people show an association between physical activity and improved cognitive performance across the lifespan, says Art Kramer, who studies how fitness can change the aging brain at the University of Illinois at Urbana-Champaign. According to recent human studies, even people who hold off on regular aerobic activity until later in life may still be able to gain from exercise in their senior years.

As people get older, it is natural for some regions of the brain to begin to shrink. For instance, studies show the hippocampus shrinks one to two percent annually in people without dementia — a loss that is associated with an increased risk for developing cognitive difficulties. Curious about whether exercise could help slow or reverse these changes, Kramer and his colleagues recruited a group of healthy, sedentary adults from ages 55 to 80 to participate in a yearlong exercise program.

These adults were divided into two teams — one spent their time walking for 40 minutes three days per week while the other performed a variety of strength and balance exercises during this time. At the start, middle, and completion of the study, the researchers used magnetic resonance imaging (MRI) to measure the volume of the hippocampus.

The size of the hippocampus increased by 2 percent on average in the adults that completed the walking regimen and memory improved. In contrast, the participants who completed a yearlong balance and strength training program experienced a 1 percent decrease in the volume of the hippocampus.

"These findings suggest that brain and cognitive health can benefit from very modest increases in exercise and physical activity," Kramer says. "It's never too late to reap the benefits of exercise."

References

Colcombe SJ, Kramer AF, Erickson KI, Scalf P, McAuley E, et al. Cardiovascular fitness, cortical plasticity, and aging. Proceedings of the National Academy of Sciences USA. Mar 2; 101(9):3316-21 (2004).

Cotman C, Berchtold N, Christie L.  Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends in Neuroscience. 9: 464-72 (2007).

Eriksson P, Perfilieva E, Björk-Eriksson T, Alborn A, Nordborg C, et al. Neurogenesis in the adult human hippocampus. Nature Medicine. 4: 1313 – 1317 (1998).     

Gómez-Pinilla F, Hillman C. The influence of exercise on cognitive abilities. Comprehensive Physiology. 3:403-428 (2013).

Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, et al. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Medicine and Science in Sports and Exercise. Aug;39(8):1423-34 (2007).

Pereira A, Huddleston D, Brickman A, Sosunov A, Hen R, et al.  An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proceedings of the National Academy of Sciences. 13: 5638-5643 (2007).

Raz N, Lindenberger U, Rodrigue KM, Kennedy KM, Head D, et al. Regional brain changes in aging healthy adults: General trends, individual differences and modifiers. Cerebral Cortex 15:1676–1689 (2005).

Rhyu IJ, Bytheway JA, Kohler SJ, Lange H, Lee KJ, et al. Effects of aerobic exercise training on cognitive function and corticol vascularity in monkeys.  Neuroscience. 4: 1239-1248 (2010).         

van Praag H, Kempermann G, Gage F. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nature Neuroscience. 2: 266-270 (1999).

Voss M, Nagamatsu, L, Liu-Ambrose T, Kramer A. Exercise, brain, and cognition across the life span. Journal of Applied Physiology. 5: 1505-1513 (2011).

Further Reading

Ratey J. Spark: The Revolutionary New Science of Exercise and the Brain. Boston, 2008.

Reynolds G. Lobes of steel. New York Times, 2007.

Rosen M. Art Kramer, neuroscientist. UC Santa Cruz, 2012.

About the Authors

Jen Uscher

Jen Uscher is a freelance science writer based in Brooklyn, New York. She has written for ScientificAmerican.com, Popular Science, APA Monitor on Psychology, the Dana Foundation, the American Committee for the Weizmann Institute of Science, and the web site of the PBS science series NOVA.

Jennifer Carr

Jennifer Carr is the former manager of science writing at the Society for Neuroscience. While working as a technician at a neuroscience lab at the University of Pennsylvania, Jennifer discovered she is happiest when communicating the excitement of scientific discovery to the general public. She has written for Kaiser Health News, The Scientist, and The Times-Picayune.

reposted from

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Contact: Latarsha Gatlin
lgatlin1@jhu.edu
443-997-9909
Johns Hopkins University 

Neuroscientists: Brain activity may mark the beginning of memories

By tracking brain activity when an animal stops to look around its environment, neuroscientists at the Johns Hopkins University believe they can mark the birth of a memory.

Using lab rats on a circular track, James Knierim, professor of neuroscience in the Zanvyl Krieger Mind/Brain Institute at Johns Hopkins, and a team of brain scientists noticed that the rats frequently paused to inspect their environment with head movements as they ran. The scientists found that this behavior activated a place cell in their brain, which helps the animal construct a cognitive map, a pattern of activity in the brain that reflects the animal's internal representation of its environment.

In a paper recently published in the journal Nature Neuroscience, the researchers state that when the rodents passed that same area of the track seconds later, place cells fired again, a neural acknowledgement that the moment has imprinted itself in the brain's cognitive map in the hippocampus.

The hippocampus is the brain's warehouse for long- and short-term processing of episodic memories, such as memories of a specific experience like a trip to Maine or a recent dinner. What no one knew was what happens in the hippocampus the moment an experience imprints itself as a memory.

"This is like seeing the brain form memory traces in real time," said Knierim, senior author of the research. "Seeing for the first time the brain creating a spatial firing field tied to a specific behavioral experience suggests that the map can be updated rapidly and robustly to lay down a memory of that experience."

A place cell is a type of neuron within the hippocampus that becomes active when an animal or human enters a particular place in its environment. The activation of the cells

helps create a spatial framework much like a map, that allows humans and animals to know where they are in any given location. Place cells can also act like neural flags that "mark" an experience on the map, like a pin that you drop on Google maps to mark the location of a restaurant.

"We believe that the spatial coordinates of the map are delivered to the hippocampus by one brain pathway, and the information about the things that populate the map, like the restaurant, are delivered by a separate pathway," Knierim said. "When you experience a new item in the environment, the hippocampus combines these inputs to create a new spatial marker of that experience."

In the experiments, researchers placed tiny wires in the brains of the rats to monitor when and where brain activity increased as they moved along the track in search of chocolate rewards. About every seven seconds, the rats stopped moving forward and turned their heads to the perimeter of the room as they investigated the different landmarks, behavior called "head-scanning."

"We found that many cells that were previously silent would suddenly start firing during a specific head-scanning event," Knierim said. "On the very next lap around the track, many of these cells had a brand new place field at that exact same location and this place field remained usually for the rest of the laps. We believe that this new place field marks the site of the head scan and allows the brain to form a memory of what it was that the rat experienced during the head scan."

Knierim said the formation and stability of place fields and the newly activated place cells requires further study. The research is primarily intended to understand how memories are formed and retrieved under normal circumstances, but it could be applicable to learning more about people with brain trauma or hippocampal damage due to aging or Alzheimer's.

"There are strong indications that humans and rats share the same spatial mapping functions of the hippocampus, and that these maps are intimately related to how we organize and store our memories of prior life events," Knierim said. "Since the hippocampus and surrounding brain areas are the first parts of the brain affected in Alzheimer's, we think that these studies may lend some insight into the severe memory loss that characterizes the early stages of this disease."

###

Other authors on this research are: Joseph Monaco, a post-doctoral fellow with the Johns Hopkins Krieger Mind/Brain Institute and the Biomedical Engineering Department at the Johns Hopkins School of Medicine; Geeta Rao, a researcher at the Mind/Brain Institute; and Eric D. Roth, an assistant professor at the University of Delaware.

This research was supported by NIH grants R01 MH094146, R01 NS039456 and P01 NS038310.

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