Building in vivo Preclinical Assays of Circuit Engagement for Application in Therapeutic Development (R01 Clinical Trial Not Allowed)

The National Institute of Mental Health (NIMH) invites applications for its funding opportunity, "Building in vivo Preclinical Assays of Circuit Engagement for Application in Therapeutic Development." This initiative focuses on developing innovative neurophysiological and behavioral measures in animals that can serve as preclinical assays for early-phase therapeutic development for mental illnesses. The goal is to establish in vivo assays that reflect clinically relevant neural processes, paving the way for translational research. The program emphasizes advancing neuroscience-based screening measures that improve the predictive value of preclinical data for treatment development, bridging gaps between preclinical animal studies and human clinical research. This opportunity supports projects encompassing three phases: optimizing neurophysiological or behavioral measures that align with clinically relevant brain processes, evaluating these measures using pharmacokinetic/pharmacodynamic studies with validated interventions, and conducting mechanistic testing of brain circuits hypothesized to underlie these measures. Proposed assays should be innovative, address functional domains disrupted in mental illnesses, and demonstrate the potential for cross-species relevance. Examples of relevant measures include EEG and MEG for brain rhythms, assays of reward learning, impulsivity, vigilance, and top-down inhibitory control, as well as measures derived from cutting-edge tools such as optogenetics or computational neuroscience. Eligible applicants include higher education institutions, nonprofits, for-profit organizations, local governments, and foreign entities. The budget is not capped but should reflect the project’s needs, with budgets under $250,000 annually suitable for single-measure projects. Projects may span up to five years. Applications must demonstrate scientific rigor, describe methodologies in detail, and include milestones for each phase. Milestones should address measure optimization, performance evaluation, mechanistic testing, and plans for dissemination. The program excludes applications focusing on human studies, animal models of mental disorders, or circadian rhythm studies. Cell culture, in vitro measures, and hypothesis-driven research unrelated to the development of screening assays are also non-responsive. All projects must include a comprehensive data sharing plan to ensure broad dissemination of findings and protocols. Applications are due February 5, 2025, June 5, 2025, or September 5, 2025, with award start dates ranging from December 2025 to April 2026. Investigators are encouraged to contact NIMH program staff early in the planning process to ensure alignment with program goals. This funding opportunity aims to enrich the toolkit for preclinical screening in mental health therapeutic development and establish assays that provide robust, translationally relevant insights.