Parallel Streams of Direct Corticogeniculate Feedback from Mid-level Extrastriate Cortex in the Macaque Monkey.

First-order thalamic nuclei receive feedforward signals from peripheral receptors and relay these signals to primary sensory cortex. Primary sensory cortex, in turn, provides reciprocal feedback to first-order thalamus. Because the vast majority of sensory thalamocortical inputs target primary sensory cortex, their complementary corticothalamic neurons are assumed to be similarly restricted to primary sensory cortex. We upend this assumption by characterizing morphologically diverse neurons in multiple mid-level visual cortical areas of the primate (Macaca mulatta) brain that provide direct feedback to the primary visual thalamus, the dorsal lateral geniculate nucleus (LGN). Although the majority of geniculocortical neurons project to primary visual cortex (V1), a minority, located mainly in the koniocellular LGN layers, provide direct input to extrastriate visual cortex. These "V1-bypassing" projections may be implicated in blindsight. We hypothesized that geniculocortical inputs directly targeting extrastriate cortex should be complemented by reciprocal corticogeniculate circuits. Using virus-mediated circuit tracing, we discovered corticogeniculate neurons throughout three mid-level extrastriate areas: MT, MST, and V4. Quantitative morphological analyses revealed nonuniform distributions of unique cell types across areas. Many extrastriate corticogeniculate neurons had spiny stellate morphology, suggesting possible targeting of koniocellular LGN layers. Importantly though, multiple morphological types were observed across areas. Such morphological diversity could suggest parallel streams of V1-bypassing corticogeniculate feedback at multiple stages of the visual processing hierarchy. Furthermore, the presence of corticogeniculate neurons across visual cortex necessitates a reevaluation of the LGN as a hub for visual information rather than a simple relay.

Morphological evidence for multiple distinct channels of corticogeniculate feedback originating in mid-level extrastriate visual areas of the ferret.

Complementary reciprocal feedforward and feedback circuits connecting the visual thalamus with the visual cortex are essential for visual perception. These circuits predominantly connect primary and secondary visual cortex with the dorsal lateral geniculate nucleus (LGN). Although there are direct geniculocortical inputs to extrastriate visual cortex, whether reciprocal corticogeniculate neurons exist in extrastriate cortex is not known. Here we utilized virus-mediated retrograde tracing to reveal the presence of corticogeniculate neurons in three mid-level extrastriate visual cortical areas in ferrets: PMLS, PLLS, and 21a. We observed corticogeniculate neurons in all three extrastriate areas, although the density of virus-labeled corticogeniculate neurons in extrastriate cortex was an order of magnitude less than that in areas 17 and 18. A cluster analysis of morphological metrics quantified following reconstructions of the full dendritic arborizations of virus-labeled corticogeniculate neurons revealed six distinct cell types. Similar corticogeniculate cell types to those observed in areas 17 and 18 were also observed in PMLS, PLLS, and 21a. However, these unique cell types were not equally distributed across the three extrastriate areas. The majority of corticogeniculate neurons per cluster originated in a single area, suggesting unique parallel organizations for corticogeniculate feedback from each extrastriate area to the LGN. Together, our findings demonstrate direct feedback connections from mid-level extrastriate visual cortex to the LGN, supporting complementary reciprocal circuits at multiple processing stages along the visual hierarchy. Importantly, direct reciprocal connections between the LGN and extrastriate cortex, that bypass V1, could provide a substrate for residual vision following V1 damage.

Analysis of macrophages and neutrophils infiltrating murine mammary carcinoma sites within hours of tumor delivery.

Here we used three different murine mammary carcinomas to study the immune environment associated with early tumor sites. While it was not surprising that the early immune response was predominated by macrophages and neutrophils, there were some novel findings at this early stage of disease. For instance, the macrophages and neutrophils expressed a mixed cytokine profile with TNF-α and TGF-ß both produced at appreciable levels. Moreover, while the cells retained their phagocytic capacity, production of reactive oxygen species by the macrophages and neutrophils was in decline. Alterations in the metabolic profile of the tumor associated macrophages were also evident with a decrease in the ATP production rate, and a higher dependence on oxidative phosphorylation for ATP production. Collectively, these data indicate a mixed phenotype of tumor-associated macrophages and neutrophils evident within hours of murine mammary carcinoma delivery.