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

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.

Keywords: anterior thalamus; entorhinal cortex; grid cells; head direction cells; hippocampus; laterodorsal thalamus; prefrontal cortex; retrosplenial cortex.

Figure 1

Schematic diagrams outlining the main connections of (A) the anteroventral (AV), (B) the anterodorsal (AD), (C) the anteromedial (AM) subnuclei of the anterior thalamic nucleus, and (D) the laterodorsal (LD) thalamic nucleus from studies in rats, cats and monkeys. All four nuclei share dense reciprocal connections to both the RSC and the hippocampal formation. Clear functionally relevant differences are apparent however, between the additional connections of each subnucleus. For example, the AM is broadly connected to many cortical sites including prefrontal, temporal and sensory cortex, whereas the AD has few cortical connections, and does not project to the anterior cingulate like the AM, AV and LD. Another critical point of difference is that all three subnuclei of the ATN receive one primary input containing mnemonically relevant information from the mammillary bodies (MB), whereas the LD receives ascending afferents from regions associated with visual processing, such as the pretectal complex. Arrowheads indicate the direction of information flow, with double headed arrows showing reciprocal connections between structures. The colored boxes indicate the three major functional processes, theta rhythm (green), head direction (gold) or visual processing (blue), associated with these four thalamocortical circuits. Structures associated with two or more of these processes are indicated by a combination of colors. The larger gray boxes group each structure into the broader category of brain region it belongs to, e.g., cortex. Additional connections also exist between cortical structures, the hippocampal formation, midbrain, and brainstem but these are not depicted here. We have also included the presubiculum and postsubiculum as separate structures but we note that the dorsal part of the presubiculum is commonly known as the postsubiculum. Additional abbreviations: Dtg, dorsal tegmental nucleus of Gudden; LD tegmental nucleus, laterodorsal tegmental nucleus; LMB, lateral mammillary bodies; MMB, medial mammillary bodies; RSC, retrosplenial cortex; TRN, thalamic reticular nucleus; vLGN, ventral part of the lateral geniculate nucleus of the thalamus; Visual cortex 18b, Brodmann area 18b; VTg ventral tegmental nucleus of Gudden.

Figure 2

Schematic representation (A) of the organization of a first order (left panel) and higher order (right panel) thalamic relay according to the Sherman and Guillery (1996) model. Panel (B) depicts a hypothetical scenario based on the work of Xiao and Barbas (2002) and Xiao et al. (2009) of the anteromedial subnucleus (AM, orange) of the anterior thalamic nuclei as a higher order thalamic relay to anterior cingulate cortex (ACg) in the macaque monkey. Panel (C) depicts a hypothetical scenario based on the work of Shibata (2000) and Thompson and Robertson (1987) of the laterodorsal thalamic nucleus (LD, orange) as a higher order relay to the dysgranular (29d) retrosplenial cortex in a rat (Shibata, 2000). In a higher order thalamic relay both a “driver” afferent from layer V of the cortex (dotted lines) and a “modulator” afferent from layer VI of cortex (short dashed lines) and the (TRN, green) innervates the thalamic relay neuron. The thalamic relay neuron then in turn projects this cortical information back to layers of cortex (large dashed lines). Projections from the brainstem reticular formation (BRF) and directly from the TRN provide additional modulation to these thalamic relay neurons (Sherman, 2017). Coronal sections for the macaque monkey (B) adapted from http://braininfo.rprc.washington.edu/PrimateBrainMaps/atlas/Mapcorindex.html. Images taken at −9 mm and −5 mm from the AC in the macaque brain. Coronal sections for the rat (C) adapted from Paxinos and Watson (1998). Images taken −6.04 mm and −2.56 mm from Bregma in the rat brain. Additional abbreviations: 29a-b, Brodmann area 29a-b, granular retrosplenial cortex; 29d, Brodmann area 29d, dysgranular retrosplenial cortex; AC, anterior commissure; AD, anterodorsal subnucleus of the anterior thalamic nuclei; AV, anteroventral subnucleus of the anterior thalamic nuclei; Fx, fornix; Cd, caudate nucleus; CM, centromedial nucleus of the thalamus; HF, hippocampal formation; MD, mediodorsal thalamus; PC, paracentral nucleus; Po, posterior thalamic group; PV, paraventricular nucleus; Re, nucleus reuniens of the thalamus; SM, stria medullaris; ST, stria terminalis; tdt, telodiencephalic fissure; VApc, ventroanterior nucleus (parvicellular); VAmc, ventroanterior nucleus (magnocellular); VI, Layer six of cortex; V, Layer five of cortex; I–IV, Layers one to four of cortex; VL, ventrolateral thalamus; VLO, oral part of the ventrolateral nucleus; VPL, ventroposterolateral thalamus; VPM, ventroposteromedial thalamus, WM, white matter.