Communicating Memory Information Between the Hippocampus and Prefrontal Cortex

Jadhav paper full image

The brain has a remarkable capacity to record our daily experiences and recall this stored information to guide our behavior. For example, every time you decide to get a cup of coffee on campus, you immediately know where to go and then step toward your destination. The ability to successfully memorize paths and navigate in the environment is fundamental for animals searching for food (see Illustration), as well as for humans surviving in a complicated environment, especially when you don’t have your smartphone to rely on, but only your brain as the inner GPS! However, how does the brain learn and remember such plans that allow us to get from one place to another?

We know that a structure in brain called the hippocampus plays an important role in encoding and storing memories. The hippocampus is thought to replay remembered experiences during fast, ripple-like brain waves, termed sharp-wave ripples (SWRs), that occur during “down-time” for the brain, i.e., offline periods during sleep and during pauses in active behavior. It has been previously shown by Jadhav and colleagues that selectively disrupting these ripple oscillations using precisely-timed electrical impulses impairs the ability of animals to learn in spatial mazes, suggesting that this “mental replay” is important for navigation and memory (Jadhav et al., 2012, Science). Notably, mental replay is not isolated activity in the hippocampus, but works together with the prefrontal cortex (PFC), the executive center of brain involved in storing memories and making decisions (Jadhav et al., 2016, Neuron). However, exactly how such memory replay supports memory processing in waking and sleep states had remained elusive.

In a new article published in the Journal of Neuroscience (Tang et al., 2017), the Jadhav lab (the team included Neuroscience graduate students Wenbo Tang and Justin Shin) used high-density electrophysiology to record large numbers of neurons in both the hippocampus and prefrontal cortex in both sleep and awake states. They discovered that as rats learned a spatial memory task, the activity in the hippocampal-prefrontal network replayed recent experiences in a precise manner during SWRs that occurred when animals paused from actively exploring the maze. This structured mental replay related to ongoing spatial behavior is ideally suited for storing and retrieving memories to inform decisions. When animals were asleep after exploring the maze, the hippocampal-prefrontal replay, however, appeared “noisy” and mixed. This replay occurring during sleep periods can support the ability of the brain to consolidate memories, by selectively integrating related memories to build a coherent map for long-term storage (see Illustration). These findings show how memory information is communicated between the hippocampus and PFC during ripple oscillations, and indicate that mental replay during sleep and awake states serve distinct roles in memory. These studies collectively provide fundamental knowledge about the neural substrates of memories. They will thus provide important insights into memory deficits that are prevalent in many neurological disorders that involve the hippocampal-prefrontal network, such as Alzheimer’s disease and schizophrenia.

Hippocampal-Prefrontal Reactivation during Learning Is Stronger in Awake Compared with Sleep States. Wenbo Tang, Justin D. Shin, Loren M. Frank and Shantanu P. Jadhav. Journal of Neuroscience 6 December 2017, 37 (49) 11789-11805.


Tenure-track faculty position in Neuroscience and Psychology

The Department of Psychology at Brandeis University invites applications for a tenure-track assistant professor position to begin in Fall 2014.  The position includes an appointment to the Neuroscience Program and to the Volen National Center for Complex Systems.  We seek an individual with an active research program that combines systems neuroscience and psychological approaches to understanding behavior and mental processes; the preferred specialty areas are learning and development, but we are open to other sub-specialties.  The position is open to applicants working with human and/or non-human animals who have shown outstanding promise as a researcher and mentor.  The successful applicant will join a vibrant research department with NIH training grants, entitled “Brain-Body-Behavior Interface in Learning and Development Across the Lifespan” and “Training in Cognitive Aging in a Social Context.”  Teaching duties will include Psychology and Neuroscience courses.  Applications, which should be submitted through AcademicJobsOnline at should include a CV, research statement, teaching statement, copies of relevant publications, and three letters of recommendation.  First consideration will be given to candidates whose applications are complete by October 1, 2013 although we will accept applications until the position is filled.
Brandeis University is an equal opportunity employer, committed to building a culturally diverse intellectual community, and strongly encourages applications from women and minority candidates.

notice reposted from the Psychology Dept. website

To sleep, perchance to learn?

Sleep deprivation is ubiquitous in today’s society, and we have all felt the effects of sleep loss on our ability to function optimally, physically and especially mentally. In particular, it has become clear that the brain requires sleep to efficiently establish many forms of long-term memory. However, it is still unknown what sleep deprivation actually does to the brain to impair its function. In a recently published review in the journal Cellular Signalling, authors Christopher G. Vecsey from Brandeis University and Robbert Havekes and Ted Abel from the University of Pennsylvania have tried to capture the current state of our knowledge about the molecular and cellular effects of sleep deprivation that could explain why sleep loss is so detrimental for memory formation. The review focuses primarily on memories for events and places, which are thought to be formed and stored in the area of the brain called the hippocampus.

A key approach to learn about the nitty-gritty effects of sleep deprivation has been research in rodents. Therefore, the authors begin by summarizing how sleep deprivation studies are carried out in rodents, and how sleep deprivation affects memory and several signaling pathways in the brain. Notably, they review the effects of sleep loss on neurotransmitter systems such as acetylcholine, glutamate, and GABA, all of which could potentially modulate learning and memory. The authors also discuss some of the newest and most exciting studies on the topic of sleep loss, including a handful of experiments in which researchers have been able to reverse the effects of sleep deprivation through pharmacological treatments. For example, the authors describe one of their own studies in which sleep deprivation in mice caused memory deficits and reduced signaling through the cAMP pathway, which is known to be crucial for long-term memory. This molecular effect was likely caused by accelerated breakdown of cAMP by phosphodiesterase 4 (PDE4). When mice were treated with a PDE4 inhibitor during the period of sleep deprivation, memory formation remained unaffected. Rescue of memory defects were also obtained in separate studies in which rodents were treated either with nicotine, caffeine, or CPT, an antagonist of the adenosine A1 receptor. Two related studies also found that the effects of sleep deprivation on memory could be ameliorated by prevention of transmitter release from cells in the brain called glia. This was the first indication that brain cells other than neurons are impacted by sleep deprivation and that they contribute to the effects of sleep loss on the ability to remember new information.

As the authors mention, goals for studies in the immediate future will be to identify additional ways that sleep deprivation affects the brain, determine why sleep deprivation targets these molecules, and discover how these targets interact with each other to impair the normal function of the brain. Finally, hopefully our growing knowledge can be used to develop treatments for the cognitive deficits produced by sleep loss in people, especially those who have impaired sleep due to a medical condition, such as insomnia, chronic pain, sleep apnea, or one of the many neurodegenerative or psychiatric disorders associated with disturbed sleep patterns.

Christopher G. Vecsey is a postdoctoral fellow in the Griffith Lab at Brandeis, where he continues to work on interactions between sleep and learning. Chris is supported by a postdoctoral fellowship from the National Institute of Mental Health.

Dynamic Coding in Neural Signals Workshop on July 29

The Center of Excellence for Learning in Education, Science and Technology (CELEST) is holding a workshop on its cross-function initiative Dynamic Coding in Neural Signals at Boston University (677 Beacon Street, Room B02) on July 29, 2011. from 1:00 – 5:45 pm. The workshop is free and open to the public. There will be talks by invited speakers from 1 – 4:15, including presentations by Don Katz (“Perceptual processing via coherent sequences of ensemble states”) and Paul Miller (“Stochastic transitions between discrete states in models of taste processing and decision-making”). a student and postdoc poster session will follow, with ample opportunity for discussion between presenters and workshop attendees.

CELEST is a joint venture of scientists at four Boston-area universities including Brandeis and is sponspored by the National Science Foundation. Robert Sekuler, Louis and Frances Salvage Professor of Psychology at Brandeis, is a co-Principal Investigator, and Biology and Neuroscience faculty Gina Turrigiano and Paul Miller are also involved in the center.

Hey – Fred ate that and lived to tell the tale

Don Katz discusses the interactions between taste, smell, and learning in a new story on BrandeisNOW.

“Rats learn what food that they like from smelling the breath of other rats,” says Katz, an associate professor of psychology and neuroscience. “A rat will essentially say, ‘Hey – Fred ate that and lived to tell the tale’ so later, when that rat is offered a choice, he will gravitate toward the food that he smelled on the other rat’s breath.”

How to tell what a rat likes: look at his face.

Brandeis hosts International Workshop on Learning and Memory

25 internationally recognized scientists gathered at Brandeis University from October 3-5, 2010, to discuss recent progress in understanding the neural mechanisms that promote learning. The workshop was sponsored by the Science of Learning Division of the National Science Foundation in a grant to Brandeis University Professor John Lisman, the Zalman Abraham Kekst Chair in Neuroscience. Lisman and Dr. Emrah Duzel, a neurologist from University College London, were the co-organizers of the workshop. Among the leading scientists attending were Mortimer Mishkin, Chief of the Cognitive Section on Neuroscience at NIMH, and the Nobel Prize recipient, Susumu Tonegawa.

The question of how the brain changes during learning has long fascinated scientists. In 1949 the Canadian psychologist, Donald Hebb, proposed that learning new associations involves changes in the strength of synapses. Subsequent work in many laboratories established that synapses do change as we learn and that the process rather closely follows the specific rule that Hebb had postulated.  Recent work, however, has revealed a limitation of Hebb’s rule; the forming of associations depends on the novelty of incoming information and on the motivation to learn, factors that Hebb’s rule cannot account for. The purpose of the workshop was to see how Hebb’s rule could be revised to take into consideration the new findings.

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