Projection motifs and wiring logic of medial pulvinar thalamocortical axons in the marmoset monkey

The medial pulvinar thalamic nucleus (MPu) is an evolutionary novelty of the primate thalamus, prominently expanded in humans. Piecemeal data from studies in various monkey species indicates that MPu axons reach prefrontal, inferior parietal, cingulate, insular or temporal areas; however, the precise wiring and functional logic of such brain-wide connections remain obscure. In marmoset monkeys (Callithrix jacchus) of both sexes, we visualized the axons originated from specific pulvinar domains by means of biotinylated dextranamine (BDA) microinjections and compared them across multiple cases. In addition, by injecting retrograde tracers in the cortical areas targeted by the pulvinar axons, we investigated the organization of projection cells within MPu and the existence of long-range branched axons. Specific projection motifs reveal a caudal MPu subnucleus that innervates inferior and ventral temporal areas, and a rostral MPu subnucleus that innervates temporal, ventral prefrontal, premotor, inferior posterior parietal and cingulate areas. We demonstrate numerous MPu neurons that innervate through branched axons prefrontal and parietal or prefrontal and temporal areas; other cells with different projection patterns are closely intermingled with them. Our findings support the notion that MPu is a hub of the brain-wide networks that support complex visual and social cognition, sensory-guided reaching, working memory, and attention. Moreover, the finding of long-range branching MPu axons and dense terminal arborizations suggest that MPu cells may regulate functional connectivity among high-level cortical areas at widely different spatial scales. Besides, the anatomical “ground truth” provided by our study is relevant for functional imaging and distributed network modelling studies. Significance statement The medial nucleus of the pulvinar complex is an evolutionary novelty of the primate thalamus and is uniquely expanded in humans. However, its functions are poorly understood, as data on its connections remain incomplete and fragmentary. Using high-resolution connection-labeling methods in marmoset monkeys, we mapped in full the thalamocortical axons arising from specific medial pulvinar domains and analyzed their branching patterns. Projection motifs reveal two main subnuclei, each targeting specific cortical networks. Moreover, we show that some pulvinar neurons simultaneously innervate distant prefrontal and parietal areas or prefrontal and temporal areas. Their connection patterns might allow medial pulvinar cells modulate, at different scales, functional connectivity in the cortical networks supporting object vision, social cognition, attention sensory-guided reaching and working memory.