Considering the Evidence for Anterior and Laterodorsal Thalamic Nuclei as Higher Order Relays to Cortex.

Brook A L Perry,Anna S Mitchell

doi:10.3389/fnmol.2019.00167

Abstract

Our memories are essential in our daily lives. The frontal and cingulate cortices, hippocampal system and medial temporal lobes are key brain regions. In addition, severe amnesia also occurs after damage or dysfunction to the anterior thalamic nuclei; this subcortical thalamic hub is interconnected to these key cortical memory structures. Behavioral, anatomical, and physiological evidence across mammalian species has shown that interactions between the anterior thalamic nuclei, cortex and hippocampal formation are vital for spatial memory processing. Furthermore, the adjacent laterodorsal thalamic nucleus (LD), interconnected to the retrosplenial cortex (RSC) and visual system, also contributes to spatial memory in mammals. However, how these thalamic nuclei contribute to memory still remains largely unknown. Fortunately, our understanding of the importance of the thalamus in cognitive processes is being redefined, as widespread evidence challenges the established view of the thalamus as a passive relay of sensory and subcortical information to the cortex. In this review article, we examine whether the anterior thalamic nuclei and the adjacent LD are suitable candidates for “higher-order” thalamic nuclei, as defined by the Sherman and Guillery model. Rather than simply relaying information to cortex, “higher-order” thalamic nuclei have a prominent role in cognition, as they can regulate how areas of the cortex interact with one another. These considerations along with a review of the latest research will be used to suggest future studies that will clarify the contributions that the anterior and LD have in supporting cortical functions during cognitive processes.

Highlights

In mammals, interconnected brain regions, including the medial temporal lobes, frontal and cingulate cortices and diencephalon, support the formation of new memories (Aggleton, 2014)
First order nuclei receive distinct fine ‘‘modulator’’ afferents from layer VI of the cortex (Sherman and Guillery, 1996; Sherman, 2016). This modulation is generally linked to the inhibitory GABA pathway passing through the thalamic reticular nucleus (TRN)
The mouse AD did not appear to conform to any of the three clusters defined by Phillips et al (2018). Further to these molecular differences, there is growing evidence that anterior nuclei (ATN) is more than a passive relay of hypothalamic and brainstem information to cortex

Summary

BACKGROUND

In mammals, interconnected brain regions, including the medial temporal lobes, frontal and cingulate cortices and diencephalon, support the formation of new memories (Aggleton, 2014). The ATN and LD sit at a convergence point within a complex array of cortical and subcortical connections (Figure 1; Aggleton et al, 2010; Jankowski et al, 2013; Dalrymple-Alford et al, 2015) These include widespread, often reciprocal, links to frontal cortex, cingulate cortex, especially retrosplenial cortex (RSC), and hippocampal formation (Shibata, 1998, 2000; van Groen et al, 2002; Shibata and Naito, 2005). Important differences between the LD, AV, AD and AM are observed in the pattern of cortical connections they receive (Figure 1) This is especially true for the AM, which is linked to many areas of PFC, including medial PFC and anterior cingulate cortex (ACg; Hoover and Vertes, 2007; Xiao et al, 2009; Jankowski et al, 2013). Only LD and AV share reciprocal connections with secondary motor cortex, but all four thalamic nuclei project to entorhinal cortex (Shibata and Naito, 2005)

SUMMARY OF THE ESTABLISHED PRINCIPLES

CONCLUDING REMARKS