TOWARD A 3D MESOSCALE ATLAS OF INTRATHALAMIC INHIBITORY INTERNEURONS IN THE HUMAN BRAIN

The thalamus is central to sensory processing and higher-order cognition. Yet the human thalamic neuronal diversity, particularly of inhibitory interneurons (ITIN), is not well characterised. This is especially important since in contrast to the commonality of the reticular thalamic nucleus ITINs, it has been shown that ITIN density increases drastically from rodent to primates, suggesting that intrathalamic ITINs are critical for supporting more complex thalamic functions. Despite prior efforts, we currently do not have a complete map of ITINs across all thalamic nuclei in humans. This limits our understanding of their potential role in health and disease. To address this gap, we aim to develop a novel 3D mesoscale atlas of the human thalamus that integrates structural and connectional organisation with detailed ITIN mapping. Our work is focused on optimising MRI and light-sheet microscopy, and Figure 1 summarises the methodology. Optimization of the clearing and staining protocol was essential for imaging aged, formalin-fixed human thalamic tissue. Our experiments determined the optimal tissue thickness for effective labelling and imaging, while minimizing the number of tissue blocks required. This approach reduces tissue loss, structural distortions, and alignment difficulties when reconstructing the complete thalamus dataset.Our datasets provide new insights into thalamic organisation and establish a foundation for mesoscale brain mapping. By integrating high-resolution connectional mapping with ITIN characterisation, this atlas aims to capture features of thalamic architecture absent from current resources and will offer a precise, anatomically grounded tool for neurosurgical planning and mechanistic studies of thalamic function.