The postnatal development of retinal projections in strepsirrhine galagos (Otolemur garnettii).

Here, we describe the postnatal development of retinal projections in galagos. Galagos are of special interest as they represent the understudied strepsirrhine branch (galagos, pottos, lorises, and lemurs) of the primate radiations. The projections of both eyes were revealed in each galago by injecting red or green cholera toxin subunit B (CTB) tracers into different eyes of galagos ranging from postnatal day 5 to adult. In the dorsal lateral geniculate nucleus, the magnocellular, parvocellular, and koniocellular layers were clearly labeled and identified by having inputs from the ipsilateral or contralateral eye at all ages. In the superficial layers of the superior colliculus, the terminations from the ipsilateral eye were just ventral to those from the contralateral eye at all ages. Other terminations at postnatal day 5 and later were in the pregeniculate nucleus, the accessory optic system, and the pretectum. As in other primates, a small retinal projection terminated in the posterior part of the pulvinar, which is known to project to the temporal visual cortex. This small projection from both eyes was most apparent on day 5 and absent in mature galagos. A similar reduction over postnatal maturation has been reported in marmosets, leading to the speculation that early retinal inputs to the pulvinar are responsible for the activation and early maturation of the middle temporal visual area, MT.

Cortical connections of the functional domain for climbing or running in posterior parietal cortex of galagos.

Previous studies in prosimian galagos (Otolemur garnetti) have demonstrated that posterior parietal cortex (PPC) is subdivided into several functionally distinct domains, each of which mediates a specific type of complex movements (e.g., reaching, grasping, hand-to-mouth) and has a different pattern of cortical connections. Here we identified a medially located domain in PPC where combined forelimb and hindlimb movements, as if climbing or running, were evoked by long-train intracortical microstimulation. We injected anatomical tracers in this climbing/running domain of PPC to reveal its cortical connections. Our results showed the PPC climbing domain had dense intrinsic connections within rostral PPC and reciprocal connections with forelimb and hindlimb region in primary motor cortex (M1) of the ipsilateral hemisphere. Fewer connections were with dorsal premotor cortex (PMd), supplementary motor (SMA), and cingulate motor (CMA) areas, as well as somatosensory cortex including areas 3a, 3b, and 1-2, secondary somatosensory (S2), parietal ventral (PV), and retroinsular (Ri) areas. The rostral portion of the climbing domain had more connections with primary somatosensory cortex than the caudal portion. Cortical projections were found in functionally matched domains in M1 and premotor cortex (PMC). Similar patterns of connections with fewer labeled neurons and terminals were seen in the contralateral hemisphere. These connection patterns are consistent with the proposed role of the climbing/running domain as part of a parietal-frontal network for combined use of the limbs in locomotion as in climbing and running. The cortical connections identify this action-specific domain in PPC as a more somatosensory driven domain.

The postnatal development of MT, V1, LGN, pulvinar and SC in prosimian galagos (Otolemur garnettii).

Considerable evidence supports the premise that the visual system of primates develops hierarchically, with primary visual cortex developing structurally and functionally first, thereby influencing the subsequent development of higher cortical areas. An apparent exception is the higher order middle temporal visual area (MT), which appears to be histologically distinct near the time of birth in marmosets. Here we used a number of histological and immunohistological markers to evaluate the maturation of cortical and subcortical components of the visual system in galagos ranging from newborns to adults. Galagos are representative of the large strepsirrhine branch of primate evolution, and studies of these primates help identify brain features that are broadly similar across primate taxa. The histological results support the view that MT is functional at or near the time of birth, as is primary visual cortex. Likewise, the superior colliculus, dorsal lateral geniculate nucleus, and the posterior nucleus of the pulvinar are well-developed by birth. Thus, these subcortical structures likely provide visual information directly or indirectly to cortex in newborn galagos. We conclude that MT resembles a primary sensory area by developing early, and that the early development of MT may influence the subsequent development of dorsal stream visual areas.

Distributions of Cells and Neurons across the Cortical Sheet in Old World Macaques.

According to previous research, cell and neuron densities vary across neocortex in a similar manner across primate taxa. Here, we provide a more extensive examination of this effect in macaque monkeys. We separated neocortex from the underlying white matter in 4 macaque monkey hemispheres (1 Macaca nemestrina, 2 Macaca radiata, and 1 Macaca mulatta), manually flattened the neocortex, and divided it into smaller tissue pieces for analysis. The number of cells and neurons were determined for each piece across the cortical sheet using flow cytometry. Primary visual cortex had the most densely packed neurons and primary motor cortex had the least densely packed neurons. With respect to differences in brain size between cases, there was little variability in the total cell and neuron numbers within specific areas, and overall trends were similar to what has been previously described in Old World baboons and other primates. The average hemispheric total cell number per hemisphere ranged from 2.9 to 3.7 billion, while the average total neuron number ranged from 1.3 to 1.7 billion neurons. The visual cortex neuron densities were predictably higher, ranging from 18.2 to 34.7 million neurons/cm2 in macaques, in comparison to a range of 9.3-17.7 million neurons/cm2 across cortex as a whole. The results support other evidence that neuron surface densities vary across the cortical sheet in a predictable pattern within and across primate taxa.

No relative expansion of the number of prefrontal neurons in primate and human evolution.

Human evolution is widely thought to have involved a particular expansion of prefrontal cortex. This popular notion has recently been challenged, although controversies remain. Here we show that the prefrontal region of both human and nonhuman primates holds about 8% of cortical neurons, with no clear difference across humans and other primates in the distribution of cortical neurons or white matter cells along the anteroposterior axis. Further, we find that the volumes of human prefrontal gray and white matter match the expected volumes for the number of neurons in the gray matter and for the number of other cells in the white matter compared with other primate species. These results indicate that prefrontal cortical expansion in human evolution happened along the same allometric trajectory as for other primate species, without modification of the distribution of neurons across its surface or of the volume of the underlying white matter. We thus propose that the most distinctive feature of the human prefrontal cortex is its absolute number of neurons, not its relative volume.

The human cerebral cortex is neither one nor many: neuronal distribution reveals two quantitatively different zones in the gray matter, three in the white matter, and explains local variations in cortical folding.

The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex) the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital) that differ in how neurons are distributed across their gray matter volume and in three zones (prefrontal, occipital, and non-occipital) that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non-occipital areas.

Cellular scaling rules for the brains of an extended number of primate species.

What are the rules relating the size of the brain and its structures to the number of cells that compose them and their average sizes? We have shown previously that the cerebral cortex, cerebellum and the remaining brain structures increase in size as a linear function of their numbers of neurons and non-neuronal cells across 6 species of primates. Here we describe that the cellular composition of the same brain structures of 5 other primate species, as well as humans, conform to the scaling rules identified previously, and that the updated power functions for the extended sample are similar to those determined earlier. Accounting for phylogenetic relatedness in the combined dataset does not affect the scaling slopes that apply to the cerebral cortex and cerebellum, but alters the slope for the remaining brain structures to a value that is similar to that observed in rodents, which raises the possibility that the neuronal scaling rules for these structures are shared among rodents and primates. The conformity of the new set of primate species to the previous rules strongly suggests that the cellular scaling rules we have identified apply to primates in general, including humans, and not only to particular subgroups of primate species. In contrast, the allometric rules relating body and brain size are highly sensitive to the particular species sampled, suggesting that brain size is neither determined by body size nor together with it, but is rather only loosely correlated with body size.