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Topological specification of connections between prefrontal cortex and hypothalamus in rhesus monkeyWells, Anne Marie 03 December 2020 (has links)
The hypothalamus is a subcortical brain region whose limits and constituent nuclei lack consensus. The hypothalamus has been linked to emotion and different states of stress, providing critical feedback about the internal environment to the prefrontal cortex, a region known for executive function within the cortex of humans. An understanding of the developmental origin of the hypothalamus can provide a basis for defining which limits and nuclei are ontologically hypothalamic, and which are not, as well as a framework for understanding its connectional relationship with other brain regions.
The Prosomeric Model (Rubenstein et al. 1994; Puelles and Rubenstein 2003; Nieuwenhuys and Puelles 2016; Puelles 2018) explains the embryological development of the central nervous system (CNS) shared by all vertebrates as a Bauplan. As a primary event, the early neural plate is patterned by intersecting longitudinal plates and transverse segments, forming a mosaic of progenitor units. The hypothalamus is specified by three prosomeres [hp1, hp2, and the acroterminal domain (At)] of the secondary prosencephalon with corresponding alar and basal plate parts, which develop apart from the diencephalon. Mounting evidence suggests that progenitor units within alar plate and basal plate parts of hp1 and hp2 give rise to distinct hypothalamic nuclei, which preserve their relative invariant positioning (topology) in the adult brain. Nonetheless, the principles of the Prosomeric Model have not been applied to the hypothalamus of adult primates.
The Structural Model (Barbas 1986; Barbas and Rempel-Clower 1997) highlights the variation of laminar structure in the grey matter of the prefrontal cortex as a basis for predicting specific cortico-cortical connections. The areas of the prefrontal cortex vary along a spectrum by number of layers, laminar definition, and cellularity of those layers. The systematic laminar patterns of different areas of the prefrontal cortex seem to be associated with differential rates of development or maturation. A topographical analysis of bidirectional projections between the prefrontal cortex and the hypothalamus was previously applied using the Structural Model (Rempel-Clower and Barbas 1998). The authors found the prefrontal cortex has highly specific projections to the hypothalamus, originating mostly from limbic orbital and medial prefrontal areas, which have lower laminar definition than other prefrontal areas. In addition, the hypothalamus has relatively specific patterns of projection to the prefrontal cortex.
We previously lacked an organizing principle to examine the specific pattern of connections between the hypothalamus and prefrontal cortex in adult rhesus monkey. In the present study, hypothalamic nuclei in the rhesus monkey (Macaca mulatta) were parcellated using classic architectonic boundaries and stains. The topological relations of hypothalamic nuclei and adjacent hypothalamic landmarks were then analyzed with homology across rodent and primate species to trace the origin of adult hypothalamic nuclei to the alar or basal plate components of hp1 and hp2. A novel atlas of the hypothalamus of the adult rhesus monkey was generated with developmental ontologies for each hypothalamic nucleus. This atlas was then applied to a topological analysis of the strength and pattern of connections between the hypothalamus and prefrontal cortex in the adult rhesus monkey. The result is a systematic reinterpretation of the adult hypothalamus of the rhesus monkey whose prosomeric ontology was used to study connections and neuraxial pathways linking the hypothalamus and prefrontal cortex. The convergence of the Prosomeric and Structural Models provides a framework through development to explain the structural patterns found in the adult primate cortex and hypothalamus, and the likely consequences of their disruption.
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