Federal Project Grant Award Summary

Yale University received a $847,792 Project Grant from the National Institute of Mental Health (NIMH) under the Mental Health Research Grants program (CFDA 93.242), effective July 1, 2026, through April 30, 2031. This award supports the development of integrated human thalamocortical assembloids—three-dimensional neural structures created through stem cell technologies—designed to produce thalamocortical oscillations that replicate human brain rhythms. The research addresses a critical gap in neurobiological understanding by creating the first human brain organoid model capable of reproducing the cortical oscillations typically observed in scalp electroencephalography (EEG), thereby providing a tractable human system for investigating the molecular, cellular, and circuit mechanisms underlying brain rhythm regulation.

The project comprises two primary aims: (1) developing human thalamic organoid and ventralized thalamic organoid assembloids to produce intrinsic thalamic network oscillations while examining the role of thalamic reticular nucleus GABAergic cells in rhythm generation, and (2) developing methods to produce thalamocortical assembloids combining human cortical organoids with thalamic components to generate thalamocortical oscillations through synaptic interactions. These deliverables advance fundamental neuroscience research with significant implications for understanding dysregulation of brain rhythms implicated in neuropsychiatric and neurodegenerative disorders, positioning findings for potential translational applications in disease modeling and therapeutic intervention development.