The medial pulvinar: function, origin and association with neurodevelopmental disorders

Abstract

The pulvinar is primarily referred to for its role in visual processing. However, the 'visual pulvinar' only encompasses the inferior and lateral regions of this complex thalamic nucleus. The remaining medial portion (medial pulvinar, PM) establishes distinct cortical connectivity and has been associated with directed attention, executive functions and working memory. These functions are particularly impaired in neurodevelopmental disorders, including schizophrenia and attention deficit and hyperactivity disorder (ADHD), both of which have been associated with abnormal PM architecture and connectivity. With these disorders becoming more prevalent in modern societies, we review the literature to better understand how the PM can participate in the pathophysiology of cognitive disorders and how a better understanding of the development and function of this thalamic nucleus, which is most likely exclusive to the primate brain, can advance clinical research and treatments.

Keywords: cognitive disorders; primate; pulvinar.

Figure 1

Architecture of the adult marmoset monkey pulvinar complex. Adjacent coronal sections through the adult marmoset brain were stained for Nissl substance (A), to stain cell bodies; modified Gallyas stain (B), to reveal myelin; acetylcholinesterase (AChE) histochemistry (C), to label cholinergic neurones; and the calcium‐binding proteins calbindin (D) and parvalbumin (E) immunohistochemistry. This combination enables the demarcation of all the subnuclei forming the pulvinar complex, including potential subdvisions within the PM (see C, arrowhead); PIcl, caudolateral inferior pulvinars; PIcm, caudomedial inferior pulvinar; PIm, medial inferior pulvinar; PIp, posterior inferior pulvinar; PL, lateral pulvinar; PM, medial pulvinar; PM‐l, lateral medial pulvinar; PM‐m, medial medial pulvinar; PM‐mc, medial central medial pulvinar. Scale bar: 1000 μm.

Figure 2

Reciprocal connectivity between the medial pulvinar and the neocortex. Injection of the retrograde fluorescent tracer cholera toxin subunit b 488 (CTb‐488) and the anterograde fluorescent tracer biotinylated dextran amine 10 kDa 488 (BDA‐10k‐488) in an adult marmoset PM using an MRI‐guided injection technique (Mundinano et al. 2016) demonstrates that PM efferents innervate cortical layers 3 and 1, and are recipients of cortical inputs primarily from neurones in layer 6, with additional weaker projections arising from neurones in layer 5. (A) CTb‐488 injected in the DLPFC area 9 reveals the complex morphology of PM neurones. Scale bars: (A) 200 μm; (B) 100 μm.

Figure 3

Schematic illustration of the cortical areas reciprocally connected with the medial pulvinar. The brain of an adult male human obtained from the Big Brain project (Amunts et al. 2013) was rendered in 3D using drishti (Limaye, 2012) and sliced in the coronal plane from the frontal lobe (a) to the occipital pole (c). Using the adult human brain reference atlas available on the Allen Brain portal ( www.brainspan.org/static/atlas), the position of cortical areas establishing reciprocal connections with the medial pulvinar (PM), based on primate connectivity studies, were delineated and highlighted. This figure illustrates the extensive network of areas that are connected through the PM. The position of the pulvinar is indicated by a white asterisk (slice b5) Scale bar: 15 mm.

Figure 4

Phylogenetic tree of medial pulvinar evolution. The medial pulvinar (PM) emerged first in primates with strepsirrhines exhibiting a rudimentary PM, and an inferior pulvinar (PI) and lateral pulvinar (PL) that have not achieved their ventral rotation (thick grey line). The evolution of PM is considered complete in haplorhines (thick black lines) based on the full rotation of the PI into a ventral position. The evolution of the PM continues over the primate lineage as suggested by its progressive expansion, occupying 40% of the human adult thalamus.

Figure 5

Development of the pulvinar in the embryonic brain. Coronal section through an embryonic marmoset brain at embryonic day (E) 80, ~ 65 days before birth, stained with the nuclear dye, Hoechst, to reveal the dense neurogenic zones lining the ventricles. The neurones populating the dorsal thalamus, including the pulvinar, originate from the layer lining the 3V along the path illustrated by the arrow on the schematic. 3V, third ventricle; Cx, cortex; GE, ganglionic eminences; LGd, dorsal lateral geniculate nucleus; LV, lateral ventricle; MD, medial dorsal nucleus; P, pulvinar; VZ/SVZ ventricular and subventricular zones. Scale bar: 1000 μm.