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The Mediodorsal (MD) thalamus that represents a fundamental subcortical relay has been underrepresented in the studies focusing on the molecular changes in the brains of subjects with alcohol use disorder (AUD). In the current study, MD thalamic regions from AUD subjects and controls were analyzed with Affymetrix Clariom S human microarray. Long-term alcohol use induced a significant (FDR ≤ 0.05) upregulation of 2802 transcripts and downregulation of 1893 genes in the MD thalamus of AUD subjects. A significant upregulation of GRIN1 (glutamate receptor NMDA type 1) and FTO (alpha-ketoglutarate dependent dioxygenase) was confirmed in western blot analysis. Immunohistochemical staining revealed similar heterogenous distribution of GRIN1 in the thalamic nuclei of both AUD and control subjects. The most prevalent functional categories of upregulated genes were related to glutamatergic and GABAergic neurotransmission, cellular metabolism, and neurodevelopment. The prevalent gene cluster among down-regulated genes was immune system mediators. Forty-two differentially expressed genes, including FTO, ADH1B, DRD2, CADM2, TCF4, GCKR, DPP6, MAPT and CHRH1, have been shown to have strong associations (FDR p < 10−8) with AUD or/and alcohol use phenotypes in recent GWA studies. Despite a small number of subjects, we were able to detect robust molecular changes in the mediodorsal thalamus caused by alcohol emphasizing the importance of deeper brain structures such as diencephalon, in the development of AUD-related dysregulation of neurocircuitry. [ABSTRACT FROM AUTHOR]

The thalamus has been implicated in many cognitive processes, including long-term memory. More specifically, the anterior (AT) and mediodorsal (MD) thalamic nuclei have been associated with long-term memory. Despite extensive mapping of the anatomical connections between these nuclei and other brain regions, little is known regarding their functional connectivity during long-term memory. The current study sought to determine which brain regions are functionally connected to AT and MD during spatial long-term memory and whether sex differences exist in the patterns of connectivity. During encoding, abstract shapes were presented to the left and right of fixation. During retrieval, shapes were presented at fixation, and participants made an "old-left" or "old-right" judgment. Activations functionally connected to AT and MD existed in regions with known anatomical connections to each nucleus as well as in a broader network of long-term memory regions. Sex differences were identified in a subset of these regions. A targeted region-of-interest analysis identified anti-correlated activity between MD and the hippocampus that was specific to females, which is consistent with findings in rodents. The current results suggest that AT and MD play key roles during spatial long-term memory and suggest that these functions may be sex specific. [ABSTRACT FROM AUTHOR]

The mediodorsal nucleus (MD) represents just one piece of a complex relay structure situated within the brain, called the thalamus. MD is characterized by its robust interconnections with other brain areas, especially with limbic-related structures. Given the close anatomo-functional relationship between the MD and the limbic system, this particular thalamic nucleus can directly influence various affective behaviors and participate in cognition. In this work, we review data collected from multiple anatomical studies conducted in rodent, human, and non-human primates, highlighting the complexity of this structure and of the neural networks in which it takes part. We provide proof that the MD is involved in the unification of several anatomical structures, being able to process the information and influence the activity in numerous cortical and subcortical neural circuits. Moreover, we uncover intrinsic and extrinsic mechanisms that offer MD the possibility to execute and control specific high functions of the nervous system. The collected data indicate the great importance of the MD in the limbic system and offer relevant insight into the organization of thalamic circuits that support MD functions. [ABSTRACT FROM AUTHOR]