Notice of NIMH's Interest in Studies of Neural Circuitry Linked to Computationally-Defined Behaviors of Relevance to Psychiatry in Rodents and Non-Human Primates

Notice Number: NOT-MH-18-036

Key Dates
Release Date: June 18, 2018

Related Announcements
None

Issued by
National Institute of Mental Health (NIMH)

Purpose

This notice serves to inform the neuroscience research community of NIMH’s interest in R21 and R01 applications proposing to develop and study novel computationally-defined behavioral assays in vertebrate animals in conjunction with measures of underlying neural circuit activity. Applications should include well-integrated experimental and theoretical components. Computational modeling should be based on experimentally-testable hypotheses of how neurobiological mechanisms relate to complex behaviors.

NIMH is interested in developing a library of novel behavioral assays in animals to assess mental-health relevant domains of function and to test hypotheses regarding neurobiological mechanisms. Current paradigms often lack the computational rigor necessary to reliably capture the richness and variability of complex, mental-health relevant behaviors. Moreover, behavioral and cognitive assays designed for testing novel drug candidates or causal interventions in rodent models (e.g., forced swim test, tail-suspension test, sucrose preference) are rarely predictive of human outcomes. Therefore, NIMH encourages application of theoretical, mathematical modeling to account for quantitative, parametric behavioral measurements in rodents and non-human primates.

Manipulations of specific cell types and neural projections continue to rapidly advance understanding of circuits underlying specific behavioral processes; however, there is an incomplete understanding of the key properties that enable associated networks to generate behaviors. Computational approaches are ideally positioned to integrate data across levels of neurobiology to probe these mechanisms and quantitatively determine critical circuit properties across levels of analysis. Theoretically-driven approaches and computational modelling are promising tools to address these difficult questions because they can identify interpretable dynamic relations between variables and quantify properties of complex systems across levels of analysis. Potential FOAs that applications could be submitted under include:

PAR-18-555- Understanding and Modifying Temporal Dynamics of Coordinated Neural Activity (R01 Clinical Trial Optional)

PA-18-350- NIMH Exploratory/Developmental Research Grant (R21 Clinical Trial Not Allowed)

PA-18-484- NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PA-18-345-NIH Research Project Grant( Parent R01 Clinical Trial Required)

For R21 applications, NIMH encourages studies that:

  • Focus on mental-health relevant domains of function in rodents and non-human primates,
  • Identify a limited set of key parameters that govern specific brain-behavioral dynamics,
  • Define mathematical relationships between these parameters that can accurately represent the empirical neurobehavioral dataset, and
  • Validate the computational model by predicting behavioral outcomes in an independent dataset.

Resulting assays and models will provide high-level objectivity and consistency, enabling a better understanding of brain-behavioral dynamics, more rigorous hypothesis generation, and stronger tests of neurobiological mechanisms.

R01 applications are expected to address the factors noted above for R21s but extend these further by:

  • Applying causal experimental manipulations (e.g., experimentally manipulating one of the model parameters to directionally manipulate the neurobehavioral outcome), or Using experimentally-grounded, biologically-realistic computational modeling to examine how dynamical interactions between molecules, cells and/or circuits impact complex behaviors.

Inquiries

Please direct all inquiries to:

Michele Ferrante, PhD
National Institute of Mental Health (NIMH)
Telephone: 301-435-6782
Email: ferrantem@nih.gov