Cellular and Molecular Biology of Complex Brain Disorders
David M. Panchision, Ph.D.
Division of Neuroscience and Basic Behavioral Science
This initiative would encourage innovative research projects to address gaps where high confidence risk factors associated with complex brain disorders have been identified, but the basic neurobiology of those factors is poorly understood. The emphasis of research will be at the interface between molecular, cellular, and/or circuit biology; higher order levels of analysis such as behavior are optional but not required. Studies may be hypothesis-testing or hypothesis-generating (i.e., discovery or survey-based). This initiative would not support applications proposing to use or develop a ‘model of’ a mental illness or syndrome (e.g., based on claims of face validity). Rather, applicants would be encouraged to address the basic molecular, cellular, and circuit mechanisms by which these risk factors can operate in the brain across the lifespan, thereby lending insight into how they might modify critical functional domains relevant to mental illness.
To gain a broader understanding of the biology underlying complex brain disorders, it is important to understand the context in which potential disease-associated alterations might occur (e.g., when, where, alone or in combination with other changes), and their impact on cellular and molecular functions and circuit properties. Relevant alterations might include: changes in signaling cascades within and between cells including second messengers, neuromodulators, neurotrophins, and ion channels downstream of receptors; protein synthesis, modification, and degradation; membrane dynamics; cellular bioenergetics; metabolic, immunological, and neuroinflammatory mechanisms; alterations in cell architecture and/or synaptic connectivity; regulation of the co-release of multiple transmitters from individual neurons; mechanisms of bidirectional signaling between neurons, glia and epithelial cells; homeostatic synaptic scaling; gut-brain interactions; changes that target sensitive periods of developmental plasticity or perturbations in circuit dynamics, such as excitatory/inhibitory balance and oscillatory activity.