CRCNS: Linking receptorarchitecture and functional brain networks across species

PROJECT SUMMARY (See instructions): Neurotransmitter receptors, varying in distribution across the neocortex, play a crucial role in modulating neural excitability and neural network communication. The relationship between receptor architecture and brain function, particularly considering the origin and evolution of the complex structure-function interplay across species, remains largely unexplored. The overarching goal of the proposed project is to bridge this gap through integration of 3D neurotransmitter receptor autoradiography with multimodal MRI across four species (humans, macaques, marmosets, rats). Towards this goal, we will reconstruct high-resolution receptor maps in rats and marmosets using a transfer-learning neural network (human and macaque data were completed). In Aim 1, we will innovate multimodal cross-species brain alignment by using graphmatching and joint-embedding algorithms to extract homologous multimodal features (i.e. receptor architecture, fMRI functional connectivity) and improve interspecies brain alignment across four species. Such alignment will provide a cross-species transformation for future translation studies using animal models. Following optimal brain alignment, Aim 2 will focus on structure-function coupling by comparing receptor and function connectivity gradients across neocortex, as well as the regional similarity between receptor lamination covariance and functional connectivity within and across species. This will uncover the common and species-specific relationship between microscale receptor architecture and macroscale functional connectivity. Finally, Aim 3 aims to link brain spatiotemporal dynamic signatures (i.e., coactivation patterns, traveling waves) with receptor architecture within and across species - providing an evolutionary perspective of the neurochemical basis for brain dynamics. The outcomes, including fMRI derivatives, 3D receptor atlases, and cross-species transformation will be shared via the PRIMatE Data Resource Exchange and the EBRAI NS platform to foster further basic and translational research in the neuroscience community.