David R. Kornack

The generation, migration, and differentiation of olfactory neurons in the adult primate brain

In adult rodents, neural progenitor cells in the subependymal (SZ) zone of the lateral cerebral ventricle generate neuroblasts that migrate in chains via the rostral migratory stream (RMS) into the olfactory bulb (OB), where they differentiate into interneurons. However, the existence of this neurogenic migratory system in other mammals has remained unknown. Here, we report the presence of a homologue of the rodent SZ/RMS in the adult macaque monkey, a nonhuman Old World primate with a relatively smaller OB. Our results—obtained by using combined immunohistochemical detection of a marker for DNA replication (5-bromodeoxyuridine) and several cell type-specific markers—indicate that dividing cells in the adult monkey SZ generate neuroblasts that undergo restricted chain migration over an extended distance of more than 2 cm to the OB and differentiate into granule interneurons. These findings in a nonhuman primate extend and support the use of the SZ/RMS as a model system for studying neural regenerative mechanisms in the human brain.

Racial differences in the distribution of posterior circulation occlusive disease

We compared clinical and arteriographic features in 27 white and 24 black patients with symptomatic posterior circulation occlusive disease. The degree of arterial stenosis was measured independently by two examiners at 12 sites within the vertebrobasilar territory. Racial comparisons were made based upon the distribution of extra- and intracranial occlusive lesions and symptomatic sites of the lesions. White patients had significantly more angina pectoris, more lesions of the origin of the left vertebral artery and more high grade lesions of the extracranial vertebral arteries. Black patients had significantly higher mean diastolic blood pressure, more diabetes mellitus, more lesions of the distal basilar artery, more high grade lesions of intracranial branch vessels and more symptomatic intracranial branch disease. Race was found to be the only factor increasing the risk of intracranial posterior circulation occlusive disease. Knowledge of the contribution of race to the distribution of posterior circulation lesions will help guide evaluation and treatment strategies for patients with vertebrobasilar occlusive disease.

Probing microtubule +TIPs: regulation of axon branching

Axon branching is vital to the development of a highly interconnected and functional nervous system. Similar to axon growth and guidance, axon branching is subject to dynamic remodeling of the neuronal cytoskeleton. Coordinated remodeling of the cytoskeleton is achieved through parallel and direct targeting of both actin filaments and a subset of highly dynamic microtubules that probe the actin-rich peripheral domains in growth cones and emerging branch sites. A growing number of extracellular cues implicated in growth cone guidance also influence axon branch behavior. Mechanistic insight into the molecular basis of growth cone steering and axon branching reveals significant similarities but also uncovers important differences between these crucial events in the establishment of neural circuits.

Neurogenesis and the evolution of cortical diversity: mode, tempo, and partitioning during development and persistence in adulthood.

The mammalian cerebral cortex varies enormously in absolute and relative size across species. These size differences reflect phyletic differences in the number and organization of cortical neurons, which in turn imply evolutionary changes in the developmental program that generates these neurons. Whereas patterns of symmetric and asymmetric modes of progenitor cell division during cortical neurogenesis are widely conserved among species, other proliferation parameters, including the timing and number of cell divisions, vary considerably. This variation contributes to the development of cortical size differences in mammals in general, and the expansion of neocortex in anthropoid primates (monkeys, apes, and humans) in particular. The disproportionate enlargement of anthropoid neocortex might also arise from regional ‘border-shifting’ within the embryonic telencephalon, causing expansion of the neurogenic region allocated for producing neocortex and concomitant diminution of neighboring olfactory regions. Neurogenesis also shows substantial phyletic differences in adult hippocampus, an archicortical structure. Therefore, variation in neurogenesis across species is not only a feature of early development, but is also a trait of adult cortical diversity.

Sexually dimorphic expression of the NGF receptor gene in the developing rat brain.

To define relations between trophic molecules and known sexually dimorphic traits in brain, we examined possible sex differences in nerve growth factor (NGF) and NGF receptor (NGF-R) gene expression in the rat cholinergic basal forebrain (BF)-hippocampal system. Hippocampal NGF mRNA levels did not differ between sexes; in contrast, BF NGF-R mRNA levels were greater in neonatal females than males, paralleling the known dimorphic development of cholinergic enzyme activity. Cerebellar NGF-R mRNA levels were also dimorphic in the neonate, suggesting that sex-specific influences may regulate trophic receptor gene expression in diverse brain systems.

The Development and Evolutionary Expansion of the Cerebral Cortex in Primates

The cerebral cortex is the crowning achievement of brain evolution and the biological substrate of human uniqueness. The techniques and concepts of modern neurobiology have given us many new insights into the developmental and evolutionary mechanisms involved in building the human cerebrum. Comparisons of the molecular and cellular events among developing human, non-human primate, and rodent embryos have revealed similarities as well as differences that are relevant for understanding the evolutionary expansion and elaboration of the cerebral cortex. Relatively small genetic differences between mammalian species are predominately expressed in the brain, and usually act during embryogenesis at the time of the progenitor’s exit from the cell cycle. In this article, the evolution of the cerebral cortex is viewed in the context of the radial unit hypothesis, the postulate of an embryonic protomap, and the concept of competitive neuronal interactions. Advances in understanding corticogenesis in the embryo provide hints of how spontaneous mutations that affect the early stages of corticogenesis may have played a role in determining the species-specific size and basic organization of the cerebral cortex.