Human thalamus in situ hybridization. Variations in distribution and gene expression level of multiple probes between control subjects
Calzavara R, Fitzpatrick JJ, Barchas JD, Bunney WE, Myers RM, Schatzberg AF, Akil H, Watson SJ
Society for Neuroscience. 2019.
The thalamus is a key node in neural network for perception, attention, cognition, emotion and is fundamental for sleep/wake cycles. Not surprisingly, the thalamus is a complex structure of multiple nuclei which are anatomically and functionally distinct. Each nucleus includes populations of different cell type which are not well known. This complexity is greatly enhanced in primates and particularly in human. The goal of our study is to generate a molecular map of the human thalamus in order to identify potential differences in thalamic gene-expression in schizophrenia. We are analyzing the distribution and mRNA expression level of selective genes throughout the thalamus (a total of 28 probes) including markers of Calbindin and Parvalbumin projection neurons as well GABAergic and Neuropeptide neurons. In particular, we aim to identify 1) thalamic region for connectivity with prefrontal cortex and 2) cell types distribution within cytoarchitectonically-defined nuclei. By using mRNA in situ hybridization throughout the extent of the human thalamus, we are systematically characterizing the impact of variables known to affect mRNA expression, including technical variables such as tissue handling and processing, and biological variables such as age, gender, cause of death (Li et al., 2004; Hagenauer et al., 2018). Given the importance of pH in the fresh-frozen human brain tissue, this variable is carefully controlled in our cohorts. Our findings suggest potential individual differences in thalamic gene expression between control subjects, in particular for some gene markers and thalamic nuclei, such as for the mRNA expression of CALB1 in the medio-dorsal nucleus. It is therefore important to recognize that there is a wider variation than expected. These variations point to our ability to capture individual differences even within the control population, and lay the groundwork for future comparisons between controls and pathological conditions such as schizophrenia.