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Understanding the brain requires studying its multiscale interactions from molecules to networks. The increasing availability of large-scale datasets detailing brain circuit composition, connectivity, and activity is transforming neuroscience. However, integrating and interpreting this data remains challenging. Concurrently, advances in supercomputing and sophisticated modeling tools now enable the development of highly detailed, large-scale biophysical circuit models. These mechanistic multiscale models offer a method to systematically integrate experimental data, facilitating investigations into brain structure, function, and disease. This review, based on a Society for Neuroscience 2024 MiniSymposium, aims to disseminate recent advances in large-scale mechanistic modeling to the broader community. It highlights (1) examples of current models for various brain regions developed through experimental data integration; (2) their predictive capabilities regarding cellular and circuit mechanisms underlying experimental recordings (e.g., membrane voltage, spikes, local-field potential, electroencephalography/magnetoencephalography) and brain function; and (3) their use in simulating biomarkers for brain diseases like epilepsy, depression, schizophrenia, and Parkinson's, aiding in understanding their biophysical underpinnings and developing novel treatments. The review showcases state-of-the-art models covering hippocampus, somatosensory, visual, motor, auditory cortical, and thalamic circuits across species. These models predict neural activity at multiple scales and provide insights into the biophysical mechanisms underlying sensation, motor behavior, brain signals, neural coding, disease, pharmacological interventions, and neural stimulation. Collaboration with experimental neuroscientists and clinicians is essential for the development and validation of these models, particularly as datasets grow. Hence, this review aims to foster interest in detailed brain circuit models, leading to cross-disciplinary collaborations that accelerate brain research.
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This content will become publicly available on March 30, 2026
Whole-brain, all-optical interrogation of neuronal dynamics underlying gut interoception in zebrafish
Abstract Internal signals from the body and external signals from the environment are processed by brain-wide circuits to guide behavior. However, the complete brain-wide circuit activity underlying interoception—the perception of bodily signals—and its interactions with sensorimotor circuits remain unclear due to technical barriers to accessing whole-brain activity at the cellular level during organ physiology perturbations. We developed an all-optical system for whole-brain neuronal imaging in behaving larval zebrafish during optical uncaging of gut-targeted nutrients and visuo-motor stimulation. Widespread neural activity throughout the brain encoded nutrient delivery, unfolding on multiple timescales across many specific peripheral and central regions. Evoked activity depended on delivery location and occurred with amino acids and D-glucose, but not L-glucose. Many gut-sensitive neurons also responded to swimming and visual stimuli, with brainstem areas primarily integrating gut and motor signals and midbrain regions integrating gut and visual signals. This platform links body-brain communication studies to brain-wide neural computation in awake, behaving vertebrates.
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- Award ID(s):
- 2235451
- PAR ID:
- 10611963
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Institution:
- bioRxiv
- Sponsoring Org:
- National Science Foundation
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