Document Type

Conference Paper

Publication Date

9-2-2026

Abstract

Down syndrome (DS) is the most diagnosed chromosomal disorder that results in intellectual disability and motor deficits. Neuronal identity changes in cognitive and motor regions of the brain have been reported in DS. However, these cellular changes have not been carefully identified across specific brain regions. The neurons of the thalamic nuclei – which are a major target of the cerebellum – are an important population that have received little attention in the field of preclinical Down syndrome research. In this review we survey the current evidence from clinical and preclinical studies regarding the role of the thalamus, especially in context to its input connections from the cerebellum. We also review potential molecular identity markers which can be used to characterize inhibitory and excitatory neurons in the cerebellum and the thalamus. Since immunohistochemistry combined with epifluorescence and confocal microscopy is a standard set of approaches to image these regions of the brain, we limit our review to these approaches. Further, we discuss machine learning tools that can be used to perform automated cell quantification and generate neuronal identity distribution profiles to define changes in the trisomic mouse brain. Studies focused on the thalamus will provide foundational knowledge of cellular changes in the Ts65Dn trisomic brain and will contribute to a deeper understanding of the neurobiological mechanisms altered in Down syndrome. Down syndrome (DS) is the most frequently diagnosed chromosomal disorder. DS is caused by trisomy of chromosome 21. The overexpression of the genes on HSA21 affects individuals with DS in various bodily systems. The changes to the cardiovascular, musculoskeletal, and neurological systems cause muscle hypotonia, cerebellar hypoplasia, and reduced neuronal density, among other symptoms (Antonarakis, et al., 2020).

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