US-French Research Proposal: Experimental and Theoretical Investigation of the Multi-Scale Emergence of Parametric Working Memory in Prefrontal Cortex Recurrent Networks

Information

  • NSF Award
  • 1608236
Owner
  • Award Id
    1608236
  • Award Effective Date
    9/1/2016 - 7 years ago
  • Award Expiration Date
    8/31/2019 - 4 years ago
  • Award Amount
    $ 610,001.00
  • Award Instrument
    Standard Grant

US-French Research Proposal: Experimental and Theoretical Investigation of the Multi-Scale Emergence of Parametric Working Memory in Prefrontal Cortex Recurrent Networks

The prefrontal cortex of the brain controls how people remember sizes of things, such as a number of items or the pitch of a sound, within a short time frame of about a few seconds. This ability, called parametric working memory (PWM), helps people to interpret their world, make decisions, and act or behave. Dysfunction in PWM may be involved in many brain diseases, including Alzheimer's disease, schizophrenia, attention deficit hyperactivity disorder, and bipolar disorders. These diseases affect more than 200 million people worldwide. Through this research project, researchers will learn more about how the prefrontal cortex controls PWM in healthy and diseased brains. With this new information, they may be able to create new treatments for many people suffering from brain diseases.<br/><br/>PWM relies on the persistent activity of neurons in the prefrontal cortex. This persistent activity is graded such that the firing rate of neurons correlates with the quantity of things to be remembered, which can emerge from network interactions with the local microcircuitry. Yet, to robustly display graded persistent activity, these networks must incorporate neurons with bistability, such that stable quiescence and activity coexist in their range of input. Neurons in the prefrontal cortex can display bistability that depends on non-selective cationic (CAN) currents activated by calcium. However, cellular bistability in the prefrontal cortex occurs under very specific experimental conditions of stimulation and neuromodulation. The researchers' overall goal is to determine whether CAN-mediated conditional bistability in the prefrontal cortex is a genuine physiological property of neurons and whether it supports graded persistent activities within local recurrent networks. They will develop a multidisciplinary research program of computational and experimental analysis to study properties ranging from molecular interactions to the behavior of neural networks. With theoretical modeling at the molecular, cellular, and network levels, extensive numerical simulations, intracellular recordings, and optogenetics, the researchers will identify and control neural substrates that mediate PWM. In this way, they will learn the causal mechanisms and dynamic principles of PWM in the prefrontal cortex, including the multi-stability that characterizes its graded persistent activity. These efforts will help researchers to better understand higher cognitive and behavioral functions and pathologies related to PWM, and also advance theories of fundamental properties in neuroscience. A companion project is being funded by the French National Research Agency (ANR).

  • Program Officer
    Aude Oliva
  • Min Amd Letter Date
    8/25/2016 - 7 years ago
  • Max Amd Letter Date
    8/25/2016 - 7 years ago
  • ARRA Amount

Institutions

  • Name
    The J. David Gladstone Institutes
  • City
    San Francisco
  • State
    CA
  • Country
    United States
  • Address
    1650 Owens Street
  • Postal Code
    941582261
  • Phone Number
    4157342000

Investigators

  • First Name
    Jeanne
  • Last Name
    Paz
  • Email Address
    jeanne.paz@gladstone.ucsf.edu
  • Start Date
    8/25/2016 12:00:00 AM

Program Element

  • Text
    CROSS-EF ACTIVITIES
  • Code
    7275
  • Text
    CRCNS
  • Code
    7327

Program Reference

  • Text
    CRCNS
  • Code
    7327
  • Text
    Understanding the Brain/Cognitive Scienc
  • Code
    8089
  • Text
    BRAIN Initiative Res Support
  • Code
    8091