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Priorities for Strategy 1.1

Updated: September, 2017

Describe the molecules, cells, and neural circuits associated with complex behaviors

NIMH encourages research on basic neuroscience processes responsible for emotion, executive function, impulsivity, social cognition, and memory. Discovery-based and hypothesis-testing studies examining mechanisms of regulation or dysregulation of these processes are of particular interest. Investigators are encouraged to integrate their research across levels of analysis, to utilize neurodevelopmental approaches, and to select appropriate biological systems for further study.

Research Priorities

  1. Determine the molecular, cellular, and systems components underlying brain connectivity and dynamic patterns of brain activity using model systems, stem cells, and human studies.

    Priority areas include:

    1. Determining the dynamic interactions of neurons, astrocytes, oligodendrocytes, microglia, and other cell types and how they contribute to information processing.
    2. Exploring the genomic, molecular, and physiologic bases of cell-to-cell variation and determining the functional consequences of this variation.
    3. Identifying the molecular mechanisms that control synaptic plasticity and circuit function.
    4. Determining the developmental processes that lead to the establishment of functional brain networks and determining the risk factors (e.g., genomic, environmental) affecting network function.
    5. Evaluating the utility of modifying network function for therapeutic benefit.
    6. Developing novel computational tools and techniques for the analysis and interpretation of neural activity including single unit, local field potentials, and other electrophysiological temporal dynamic patterns.
    7. Developing, optimizing, utilizing, and integrating neuroanatomical approaches to map neural circuits at micro-, meso-, and macro-scales.

  2. Identify the mechanisms responsible for establishing and maintaining circuits.

    Priority areas include:

    1. Investigating molecular and cellular processes involved in regulating the development and integration of diverse neuronal and glial cell types relevant to cognitive, affective, and social functioning.
    2. Investigating the signaling networks and plasticity mechanisms that mediate adaptive changes in circuits and how alterations may lead to maladaptive behaviors.
    3. Identifying and experimentally validating computational algorithms that the brain uses for affective, cognitive, and social processing; in particular, the neural activity patterns, such as oscillatory signals that may be providing the scaffolding for optimal neural processing.
    4. Determining the neurophysiological rules that govern how and when the brain switches among states (e.g., switching from memory encoding to recall).
    5. Developing and validating experimentally grounded theories for how the brain computes affective, cognitive, and social functions across all spatiotemporal scales and levels of neurobiological abstraction.
    6. Understanding the structural and functional maturation of specific brain circuits that contribute to both normal and maladaptive cognitive, affective, and social behaviors.

  3. Identify and validate novel assays to quantify changes in the activity of molecules, cells, and circuits.

    Priority areas include:

    1. Developing assays that interrogate key regulators of cellular communication using in situ and circuit-based models for screening, target discovery, and development of novel probes of cell function.
    2. Improving human cell-based assays using induced pluripotent stem cells (iPSCs) or other cellular models for studying the molecular bases of mental illnesses, with an emphasis on optimizing robustness and reproducibility, and fidelity to in-vivo human cell phenotypes, three-dimensional organization, and/or circuit function.
    3. Developing novel imaging tools with higher spatial and temporal resolution for visualization and analyses of brain structure and function, with particular interest in advancing real-time measurement approaches.
    4. Developing non-invasive tools for interrogating and manipulating brain circuit function for therapeutic purposes.
    5. Validating novel and objective measures of circuit function and synaptic plasticity in humans and experimental systems as research tools and for assessing therapeutic targets.
    6. Overcoming the significant barriers and limitations of standard behavioral batteries used in preclinical animal studies by developing and testing novel, objective, circuit-based behavioral and physiological measures linked to functional domains disrupted in mental illnesses.
    7. Advancing novel assays and tools to develop biomarkers of disease and for therapeutic discovery.

  4. Elucidate the basic biology linking changes in molecular-, cellular-, and circuit-based targets to alterations in complex behaviors.

    Priority areas include:

    1. Utilizing appropriate experimental systems for studying mental health-relevant phenotypes to understand conserved and/or convergent neurobiological mechanisms, as well as to gain insight into processes and circuitry that are unique to humans.
    2. Investigating the role of coordinated neural activity in normal cognitive, affective, and social processes, and aberrant processes in mental illnesses.
    3. Developing novel computational modeling approaches to understand how changes in molecular and cellular processes relate to changes in circuit function and behavior.
    4. Advancing mechanistic approaches to understand fundamental processes relevant to emotional and cognitive disorders. Animal studies using system level approaches will be prioritized over studies relying on traditional behavioral tests (e.g., tail suspension, forced swim, amphetamine-induced hyperactivity).