EX VIVO MAPPING OF NIGRO-THALAMIC DOPAMINERGIC TERMINALS REVEALS REGIONAL SPECIALIZATION AND SYNAPTIC MARKERS IN THE HUMAN THALAMUS

Cirillo G¹, Montella M², La Mantia E², Tedesco I², De Luca C¹, Virtuoso A¹, De Angelis F¹, Riccio L¹, Esposito F³, Cirillo M³, Franco R² and Papa M¹ | ¹Division of Human Anatomy, Neuronal Networks Morphology & Systems Biology Lab, Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli, Naples, Italy; ²Division of Pathology, Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli, Naples, Italy; ³Department of Advanced Medical and Surgical Sciences, Advanced MRI Research Center, University of Campania Luigi Vanvitelli, Naples, Italy

The thalamus plays a crucial role in integrating subcortical inputs and relaying them to cortical circuits, yet the extent and specificity of dopaminergic innervation to human thalamic nuclei remain incompletely understood. Recent tractographybased studies suggest the existence of direct nigro-thalamic pathways, but direct histological evidence is still limited. In this study, we provide an ex vivo mapping of dopaminergic projections to the human thalamus using high-resolution immunohistochemistry and confocal microscopy. Human brain specimens were processed to detect multiple dopaminergic markers, including tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), and aromatic L-amino acid decarboxylase (AADC), across anatomically defined thalamic nuclei. Multilabel immunofluorescence and 3D reconstruction allowed precise identification of axonal arborization and synaptic varicosities within the mediodorsal (MD), and ventral anterior (VA)/ventral lateral (VL) nuclei. Quantitative analysis revealed a significant expression of TH+/VMAT2+ fibers and D2R staining in the MD/VA/VL nuclei, supporting the notion of region-specific dopaminergic input. These results provide the first immunohistological confirmation of selective dopaminergic innervation of the human thalamus. This structural evidence complements prior neuroimaging findings and suggests a potential role for the nigro- thalamic pathway in modulating thalamo-cortical circuits involved in executive and cognitive functions.