Abstract
Human thalamus gene-expression highlights functional nodes in thalamocortical circuits vulnerable in schizophrenia
Calzavara R, Akil H, Barchas JD, Bunney WE, Lee FS, Myers RM, Schatzberg AF, Watson SJ Jr
Society for Neuroscience. 2018.
Abstract
Perception, attention, cognition and motivation are affected in schizophrenia. Those functions are processed throughout a brain-wide network which critically involved cortical connectivity with the thalamus. Increasing evidence implicates thalamic dysfunction in schizophrenia, although the role of specific nuclei is not established. In our study, we are generating a molecular mapping of the whole human thalamus to identify gene-expression markers of thalamic neurons and their regional or nuclear distributions. We used mRNA in situ hybridization for selective markers throughout the thalamus. Our gene-expression map of the human thalamus highlights critical differences within the cytoarchitectonic nuclear boundaries. This is the case for the medio-dorsal (MD) nucleus which sub-regions feature specific markers differentially expressed. While the medial part of MD highly express PVALB (parvalbumin), the lateral part of MD has a lower expression of PVALB and little or none expression of CALB1 (calbindin). The latter region is primary connected to the dorsolateral prefrontal cortex (DLPFC), which is considered key for executive functions. Interestingly, this MD sub-region was found to be selectively impaired in post-mortem studies in schizophrenia (Popken at al., 2000). Similarly, within the pulvinar complex, the anterior and medial pulvinar nuclei are characterized by a very dense PVALB expression. The pulvinar, which is one of the largest areas in the human thalamus, is primarily connected to posterior parietal cortex but also to the DLPFC and is recognized for its role in attention and perception. The intralaminar nuclei can also been characterized on the basis of their genetic markers. The anterior nuclei paracentral and central lateral express a combination of calcium-binding proteins, neurotransmitter and neuropeptides markers. On the contrary, the caudal intralaminar nuclei parafascicularis and centro-median do not express these markers. These molecular features of the human thalamus are relevant in understanding thalamocortical connectivity and its evolution and development in mammals, particularly in primates. Moreover, our findings aim to undercover critical thalamic nodes, circuits and cells types, potentially vulnerable in schizophrenia.