NIH/NIMH - Basic Neurodevelopmental Biology of Brain Circuits and Behavior (R01, R21 Clinical Trial Not Allowed)

The following description was taken from the R01 version of this FOA.

This Funding Opportunity Announcement (FOA) invites research projects focused on the dynamic and mechanistic links between the maturation of brain circuits and behaviors across development in rodents and non-human primates. The goal is to build a foundation for understanding how interactions within and among brain regions change over pre- and post-natal development, allowing for the emergence of cognitive, affective and social behaviors. To this end, projects supported will focus on neurodevelopmental trajectories in rodents or non-human primates and investigate questions using in vivo neural measures in awake, behaving animals. This FOA uses the R01 grant mechanism, whereas its companion funding opportunity seeks shorter, more exploratory or higher-risk R21 grant applications.

Background

Studies linking basic neurodevelopmental concepts and approaches with mental-health relevant behavioral questions are critical to the field of mental health research. The problems with memory, executive functions, affect regulation, and social interaction seen in psychiatric disorders are most closely linked to neural circuit organization and function. However, our understanding of the timing, trajectories, and mechanisms involved in the normative development of neural circuits that subserve these complex behaviors is lagging. We need more basic research at the level of neural circuits and systems to bridge the gap between genetic and molecular-level events and the development of clinical signs and symptoms.

Research Objectives

This FOA encourages projects, using in vivo measures in awake, behaving rodents and non-human primates, that propose to: 1) examine the pre- and post-natal developmental trajectories of neural circuits associated with formation, maintenance and plasticity of cognitive, emotional and social behaviors; 2) implement new approaches, longitudinal designs, and/or causal manipulations to study changes in these networks across developmental trajectories; AND/OR 3) investigate, in animals, processes that have been robustly associated with dysfunctions in neurodevelopmental trajectories and/or mental-health relevant behaviors in humans.

Application of computational modeling approaches, to better delineate critical neurodevelopmental parameters and/or to predict the dynamics of behavior changes with development, are encouraged. The use and application of newly-developed tools, such as those developed through NIH BRAIN Initiative, to better understand a specific neurodevelopmental question is encouraged. Tool development, per se, would not meet the goals and objectives of this FOA.

Applications should include all three of the following experimental approaches:

Experiments in rodents or non-human primates. Investigators should justify their choice of species within the framework of mental-health relevant behaviors and demonstrate that the experimental paradigms used are appropriate to the species studied. Manipulations and measures should reflect underlying questions about the neural circuit under study.
Focus on a neurodevelopmental trajectory, by inclusion of at least three time-points. Time points can range from pre-natal development to early adulthood. In addition to considering the relevance of chosen time-points to mental health, investigators should justify their choice of time-points in relation to known or hypothesized developmental events or transitions in the species under study.
Concurrent behavioral and brain measures. In vivo neural measures of circuits function in awake-behaving animals are required. Mechanistic studies should include a careful theoretical and experimental decomposition of behavior and state-of the art neuroscience techniques designed to elucidate neural algorithms that generate behavior.

Data Rigor: Translating discoveries into evidence-based treatments is predicated on the existence of strong, well powered, adequately controlled, and replicated data. In addition, the value of such research is greatly enhanced when detailed information is made available about study design, execution, analysis and interpretation. Examples of critical elements are detailed in NOT-OD-15-103.

Specific Areas of Research Interest

Examples of specific research questions of interest to NIMH include, but are not limited to, the following:

How do circuits or systems underlying complex, mental-health relevant behaviors–such as attention, working memory, episodic/spatial memory, executive function, social cognition, emotion regulation, or reward and motivation–vary across development in rodents or non-human primates?
How do developmental changes in excitatory/inhibitory balance impact circuits that underlie cognitive, affective, or social functions?
How does information processing by neural networks change over the course of pre- and/or post-natal development?
How does developmental experience affect circuit function beyond anatomical maturation?
What periods in the developmental trajectory of neural circuits and mental-health relevant behaviors are the most amenable for therapeutic interventions?
How do developmental changes in the anatomical connectivity of neural circuits lead to emergent neurophysiological properties?
What are the time windows and mechanisms for plasticity in specific circuits underlying cognitive, affective, or social behaviors?
How do developmental changes in network dynamics and/or temporal coordination of neural activity lead to changes in cognitive, social, and affective behaviors?

Areas of lower priority for this FOA include:

Neurodevelopment of circuits associated with sensory or motor functions; homeostatic processes such as feeding behaviors, thermoregulation, circadian rhythms and sleep; sexual behaviors or classical conditioning.
Studies of early life stress, which are well represented within the current NIMH portfolio.
Studies seeking to recapitulate Diagnostic and Statistical Manual (DSM) diagnoses or to fully represent human psychiatric conditions.
Studies of the neurodevelopmental effects of approved pharmacotherapies or putative environmental toxins.

Deadline: February 4, 2019

URLs:

Filed Under: Funding Opportunities

NIH/NIMH – Basic Neurodevelopmental Biology of Brain Circuits and Behavior (R01, R21 Clinical Trial Not Allowed)