Abstract

Anatomical Mapping and Gene Expression Patterns of the Human Thalamus Midline Nuclei

Medina A, Calzavara R, Bunney WE, Bunney B, Myers RM, Schatzberg A, Barchas JD, Lee FS, Akil H, Watson SJ
50th Annual Meeting of the Society for Neuroscience, Virtual. 2021.

The thalamus is generally considered as a relay center, a hub of sorts where information is collected and processed, then transmitted to specific areas of the cerebral cortex. In fact, the thalamic areas dedicated to sifting motor and sensory information constitute the majority of the structure’s mass. However, small, specific subnuclei within the thalami appear to be involved in operations pertinent to the limbic system and connect to subcortical limbic structures. The most recognizable of them is the Paraventricular Nucleus (PVT). In humans, the PVT is a thin cellular cluster located along the edge of the third ventricle. Embryologically, this nucleus develops as part of the epithalamus, along with the pineal gland and the habenular nuclei. Therefore, it can be expected that its connectivity and function differ from the majority of thalamic structures. And yet, the human PVT is hardly distinguishable histologically from the neighboring nuclei. In this study, we aim to gain some insight into the functionality of the human PVT and the similarities or differences it may have with surrounding structures by comparing their gene expression patterns. Materials and Methods: Human brain blocks containing the thalamus were obtained from the Brain Donor Program at the University of California, Irvine by agreement with the Pritzker Neuropsychiatric Consortium. Five subjects with no history of psychiatric or neurological disease were used for this study. Variables that could alter gene expression patterns were controlled for, so all samples used had a tissue pH above 6.5 and agonal factor scores (AFS) of zero. The fresh-frozen blocks were sectioned at 10um and serial sections were processed for acetylcholinesterase stain, Kluver/Luxol Fast Blue stain, and different in situ hybridization probes including calcium-binding proteins, transcription factors, and neurotransmitter-related enzymes. Results: the combined use of histological stains and in situ hybridization allowed us to discern the distribution of midline thalamic nuclei while also providing insights into the possible functional relationships between them, i.e. areas that appear histologically indistinguishable from one another show divergent gene expression patterns that hint at discreet functional differences.