The role of long-range connections on the specificity of the macaque interareal cortical network.

We investigated the influence of interareal distance on connectivity patterns in a database obtained from the injection of retrograde tracers in 29 areas distributed over six regions (occipital, temporal, parietal, frontal, prefrontal, and limbic). One-third of the 1,615 pathways projecting to the 29 target areas were reported only recently and deemed new-found projections (NFPs). NFPs are predominantly long-range, low-weight connections. A minimum dominating set analysis (a graph theoretic measure) shows that NFPs play a major role in globalizing input to small groups of areas. Randomization tests show that (i) NFPs make important contributions to the specificity of the connectivity profile of individual cortical areas, and (ii) NFPs share key properties with known connections at the same distance. We developed a similarity index, which shows that intraregion similarity is high, whereas the interregion similarity declines with distance. For area pairs, there is a steep decline with distance in the similarity and probability of being connected. Nevertheless, the present findings reveal an unexpected binary specificity despite the high density (66%) of the cortical graph. This specificity is made possible because connections are largely concentrated over short distances. These findings emphasize the importance of long-distance connections in the connectivity profile of an area. We demonstrate that long-distance connections are particularly prevalent for prefrontal areas, where they may play a prominent role in large-scale communication and information integration.

Induced Cognitive Impairments Reversed by Grafts of Neural Precursors: A Longitudinal Study in a Macaque Model of Parkinson's Disease.

Parkinson's disease (PD) evolves over an extended and variable period in humans; years prior to the onset of classical motor symptoms, sleep and biological rhythm disorders develop, significantly impacting the quality-of-life of patients. Circadian-rhythm disorders are accompanied by mild cognitive deficits that progressively worsen with disease progression and can constitute a severe burden for patients at later stages. The gold-standard 6-methyl-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) macaque model of PD recapitulates the progression of motor and nonmotor symptoms over contracted periods of time. Here, this multidisciplinary/multiparametric study follows, in five animals, the steady progression of motor and nonmotor symptoms and describes their reversal following grafts of neural precursors in diverse functional domains of the basal ganglia. Results show unprecedented recovery from cognitive symptoms in addition to a strong clinical motor recuperation. Both motor and cognitive recovery and partial circadian rhythm recovery correlate with the degree of graft integration, and in a subset of animals, with in vivo levels of striatal dopaminergic innervation and function. The present study provides empirical evidence that integration of neural precursors following transplantation efficiently restores function at multiple levels in parkinsonian nonhuman primates and, given interindividuality of disease progression and recovery, underlines the importance of longitudinal multidisciplinary assessments in view of clinical translation.

Portal sensing of intestinal gluconeogenesis is a mechanistic link in the diminution of food intake induced by diet protein.

Protein feeding is known to decrease hunger and subsequent food intake in animals and humans. It has also been suggested that glucose appearance into portal vein, as occurring during meal assimilation, may induce comparable effects. Here, we connect these previous observations by reporting that intestinal gluconeogenesis (i.e., de novo synthesis of glucose) is induced during the postabsorptive time (following food digestion) in rats specifically fed on protein-enriched diet. This results in glucose release into portal blood, counterbalancing the lowering of glycemia resulting from intestinal glucose utilization. Comparable infusions into the portal vein of control postabsorptive rats (fed on starch-enriched diet) decrease food consumption and activate the hypothalamic nuclei regulating food intake. Similar hypothalamic activation occurs on protein feeding. All these effects are absent after denervation of the portal vein. Thus, portal sensing of intestinal gluconeogenesis may be a novel mechanism connecting the macronutrient composition of diet to food intake.

Anatomy of hierarchy: feedforward and feedback pathways in macaque visual cortex.

The laminar location of the cell bodies and terminals of interareal connections determines the hierarchical structural organization of the cortex and has been intensively studied. However, we still have only a rudimentary understanding of the connectional principles of feedforward (FF) and feedback (FB) pathways. Quantitative analysis of retrograde tracers was used to extend the notion that the laminar distribution of neurons interconnecting visual areas provides an index of hierarchical distance (percentage of supragranular labeled neurons [SLN]). We show that: 1) SLN values constrain models of cortical hierarchy, revealing previously unsuspected areal relations; 2) SLN reflects the operation of a combinatorial distance rule acting differentially on sets of connections between areas; 3) Supragranular layers contain highly segregated bottom-up and top-down streams, both of which exhibit point-to-point connectivity. This contrasts with the infragranular layers, which contain diffuse bottom-up and top-down streams; 4) Cell filling of the parent neurons of FF and FB pathways provides further evidence of compartmentalization; 5) FF pathways have higher weights, cross fewer hierarchical levels, and are less numerous than FB pathways. Taken together, the present results suggest that cortical hierarchies are built from supra- and infragranular counterstreams. This compartmentalized dual counterstream organization allows point-to-point connectivity in both bottom-up and top-down directions.