BRAIN Initiative: Integrative Team-Research BRAIN Circuits Program - iBCP (RM1 Clinical Trial Not Allowed)

The iBCP aims to understand how the nervous system gives rise to mental experience and behavior. A multi-level understanding of central nervous system (CNS) function is essential for identifying critical circuits involved in health and disease, and for advancing our ability to monitor and modulate neural circuits for both basic and translational applications.

Despite rapid advances in molecular, cellular, systems, and computational neuroscience, achieving a comprehensive understanding of brain function remains hindered by persistent methodological, conceptual, and disciplinary barriers within and between different levels of analysis. Technically, for example, fully mapping and interpreting the activity patterns of heterogeneous cell types with sub-millisecond temporal resolution in behaving animals remains a challenge. Conceptually, insights into how cellular heterogeneity and connectivity relate to dynamic neural processes and computations that underpin behavior remain limited. Moreover, scientific progress often occurs in disciplinary silos, hampering integration across levels of analysis.

The BRAIN Initiative fosters cross-disciplinary collaboration, yet transdisciplinary integration that enables, for example, a comprehensive linking of cellular components to circuit function and behavior, remains a major hurdle. While molecular and cellular neuroscience offers detailed "parts lists" and targeted manipulation tools, the role of cellular heterogeneity in complex neural computations is not well understood. Conversely, systems neuroscience provides powerful methods for analyzing population-level dynamics but often lacks the cell-type specificity necessary for mechanistic insight.

The iBCP directly addresses this challenge by emphasizing the need for dynamic circuits- and systems-level investigations that incorporate emerging knowledge and data on circuit components, including cell types and connectivity. As this is a significant challenge in neuroscience, the BRAIN Initiative now seeks to support development of innovative conceptual and theoretical frameworks, and cutting-edge approaches, both experimental and computational, to understand brain function holistically, from its circuit components to behavior output.

Deliverables from this effort are expected to advance our ability to investigate and understand how the CNS encodes, processes, and transmits information across spatial (cell to brain region) and temporal (milliseconds to behavioral timescales) dimensions. These will also lead to mechanistic, biologically grounded explanations of CNS function, ultimately revealing how cellular-level interventions produce circuit- and behavior-level effects and offering new targets and insights for treating dysfunction.