Differentiation Of Cortical Areas Research Articles

How the parcellation theory of comparative forebrain specialization emerged from the Division of Neuropsychiatry at the Walter Reed Army Institute of Research

ABSTRACT The Golgi method gave birth to modern neuroscience. The Nauta method, developed in a novel Army think tank at the Walter Reed Army Medical Center, was the next major breakthrough before neuroscience emerged as a separate discipline. Dr. Walle Nauta’s (1916–1994) method allowed for the first time the ability to trace interneuronal connections accurately to their termination. The think tank, created by Dr. David Rioch (1900–1985), provided a unique intellectual environment for interdisciplinary neuroscience research, the first of its kind. Rioch hired exceptional senior faculty and recruited outstanding young investigators who were drafted into the Army, typically after finishing their M.D.s or Ph.D.s, and were interested in brain research. Many of these young investigators went on to illustrious careers in neuroscience. I worked with Walle Nauta at a time when the technique was first being applied to nonmammalian vertebrate brains. Along with other Army draftees, I was encouraged to pursue my own research interests. This led me on a quest to understand interspecific variability of connections in relation to evolution and ontogeny of the brain. By 1980, I had found that the variability of all known connections could be explained by a theory to the effect that new structures such as the neocortex were not formed by one system invading another and mingling, as Clarence Luther Herrick (1858–1904) had proposed, but by selective proliferation and differentiation sometimes involving the select loss of connections to reduce cross-modality interference as in the case of the parcellation and differentiation of cortical areas. The resulting parcellation theory predicts that elements of a primordial neocortex existed from the beginning of vertebrate evolution and did not originate by an invasion of nonolfactory modalities into the olfactory lobe, as commonly believed before the introduction of the Nauta method. This theory would not have been created if it were not for the brilliant environment that was Walter Reed in the 1960s.

Cell-Cycle Kinetics of Neocortical Precursors Are Influenced by Embryonic Thalamic Axons

Thalamic afferents are known to exert a control over the differentiation of cortical areas at late stages of development. Here, we show that thalamic afferents also influence early stages of corticogenesis at the level of the ventricular zone. Using an in vitro approach, we show that embryonic day 14 mouse thalamic axons release a diffusable factor that promotes the proliferation of cortical precursors over a restricted developmental window. The thalamic mitogenic effect on cortical precursors (1) shortens the total cell-cycle duration via a reduction of the G(1) phase; (2) facilitates the G(1)/S transition leading to an increase in proliferative divisions; (3) is significantly reduced by antibodies directed against bFGF; and (4) influences the proliferation of both glial and neuronal precursors and does not preclude the action of signals that induce differentiation in these two lineages. We have related these in vitro findings to the in vivo condition: the organotypic culture of cortical explants in which anatomical thalamocortical innervation is preserved shows significantly increased proliferation rates compared with cortical explants devoid of subcortical afferents. These results are in line with a number of studies at subcortical levels showing the control of neurogenesis via afferent fibers in both vertebrates and invertebrates. Specifically, they indicate the mechanisms whereby embryonic thalamic afferents contribute to the known early regionalization of the ventricular zone, which plays a major role in the specification of neocortical areas.