A s part of a larger study of the development of postnatal rat cerebral cortex, this report deals with the maturation of the cortex as a tissue from birth to twenty-one days of age. The changes in the numerical density of cells and blood vessels and the thickness of the cortex at successive ages were followed on light micrographs, and both were related to the ultrastructural observations on routine electron microscopic preparations. The maturation of the cortex is divided into two periods: The first ten days during which the growth to adult dimensions occurs and few patent blood vessels but large extracellular spaces are to be found, and the second ten days in which the majority of the vessels develop patent lumina, the perivascular sheath of astrocyte end-feet develops, and the large extracellular spaces disappear concomitant with the maturation of the neuropil.The blood vessels appear to develop during the first ten days as solid cords of mesodermal elements which form a network of primordial vessels with thick walls and slit-like lumina containing a flocculent material. The formation of a blood filled, patent lumen apparently occurs synchronously over a brief period of time for the majority of the vessels during the early part of the second ten-day period. The basal lamina is ill-defined initially but takes on mature appearance parallel with the development of the pcrivascular glial sheath.The volume of the extracellular space was found to be largest during the phase of rapid growth of axons and dendrites when few patent vessels exist. The disappearance of these large extracellular spaces during maturation of the blood vessels and neuropil is discussed i n terms of the possible artifactitious nature of these spaces in both immature and mature cortex.

The postnatal development of the retina in control (CBA/S) and rodless (CBA/Ki) mice was studied by light and electron microscopy. In the control mice, the major increase in retinal thickness occurs between birth and seven days. The inner and outer segments begin to grow into the optic ventricle between seven and ten days with their most rapid growth occurring between 12 to 15 days; by 35 days the retina appears mature. During development, the nuclear layers become thinner while the optic ventricle (layer of rods) and the plexiform layers become thicker. At birth, the mutant or rodless retina is indistinguishable from the control; however, the inner and outer segments fail to develop beyond the primitive seven-to ten-day stage. At 15 days the outer nuclear layer becomes reduced to only a few nuclei in thickness. Many degenerating elements are found in the cavity of the optic ventricle and in the outer nuclear and plexiform layers. By 35 days the mutant retina lacks photoreceptors and is reduced in thickness to less than that at birth. The pigment epithelium is heightened in regions where degeneration is incomplete but becomes highly attenuated in regions where visual cell degeneration is complete. The optic ventricle contains the villous processes of the pigment epithelium and the fringe processes of the Miiller cells. The outer limiting membrane is contiguous with remnants of the outer plexiform layer. Between the outer plexiform layer and the inner limiting membrane, the mutant retina is normal in appearance and dimension. The delayed appearance of the smooth endoplasmic reticulum of the pigment epithelium is implicated in the failure of outer segment maturation. The role of both Miiller and pigment epithelial cells in removal of the products of retinal degeneration is discussed.During a study in the Kirschbaum Memorial Laboratory concerned with feeding patterns in different strains of inbred mice, it was found that the CBA/Ki strain showed a "freely running" circadian rhythm relative to day and night differences in food intake (Liebelt and Perry, '67; Ishiki, '68). This behavior was in contrast to the nocturnal pattern of food intake seen in CBA/S mice as well as in several other strains. Electroretinographic examination of both strains revealed the absence of the "a" wave in the CBA/Ki strain mice although it was present in the CBA/S strain (Ishiki, '68). Histological studies demonstrated that the retinae of the CBA/Ki strain lacked the photoreceptor layer whereas this layer was intact in the CBA/S strain of mice. A further compari-AM. J. ANAT., 133: 179-212.son of these two strains has been described elsewhere (Staats, '67).Keeler ('27) reported on inheritance of a retinal abnormality in white mice in which the retina lacked rods and possessed one to three cell layers in the outer nuclear layer. Genetic and developmental studies indicated that this rodless condition was hereditary and resulted from a failure of the photoreceptor layer to differentiate. Later, Bruckner ('51) reported a somewhat simil...

The differentiation of spongioblasts from undifferentiated cells and into neuroglial cells has been studied in the postnatal rat cerebral cortex with the electron microscope. The nuclei of all the non-neural elements are characterized by clumping of dense chromatin, especially near the nuclear envelope. The undifferentiated cells possess only a thin rim of perinuclear cytoplasm containing few organelles. Spongioblasts are characterized by an increased number of cytoplasmic organelles, mostly mitochondria and Golgi complex, and by the growth of processes. These cells mature and take on either the features of oligodendrocytes or astrocytes. The multiple oligodendrocyte processes are thin and branching and develop intimate contacts with the developing axons. Early stages of myelination are characterized by the envelopment of axons by oligodendrocyte processes which overlap each other to form inner and outer tongues that are characteristic of central nervous system myelin. Astrocytes can be distinguished by the presence of cytoplasmic glycogen particles and fibrils. Processes of these latter cells develop intimate relations with the developing blood vessels.

The differentiation and maturation of the neurons of rat cerebral cortex during the first three weeks of postnatal life has been studied with the light and electron microscopes. At birth, the superficial cortex is largely made up of undifferentiated cells, tightly packed together in vertical columns between which the developing process and blood vessels, and relatively extensive extracellular spaces are found. During the first two weeks, these cells differentiate into either neuroblasts and neurons, or into spongioblasts and neuroglia. In the case of neurons but not neuroglia, this maturation occurs in a gradient from the depths toward the surface. The round undifferentiated cells are characterized by an absence of processes, a thin rim of perinuclear cytoplasm containing few organelles, and a peripheral clumping of condensed nuclear chromatin. The differentiating neuroblasts display increasing numbers of cytoplasmic organelles, especially endoplasmic reticulum, evenly dispersed nuclear chromatin, and presumptive apical dendrites. The rough endoplasmic reticulum of neuroblasts become swollen during the transition into neurons during the second week. The endoplasmic reticulum forms subsurface cisterns that transiently evaginate the cell membrane, forming conspicuous diverticuli in the neuropil at the same time that the cells display an increase of cytoplasmic matrix density and increasing numbers of ribosomes. During the three weeks following birth, organelles increase in number and complexity, synapses develop, the extracellular spaces disappear, and the maturing neurons become separated from one another by the growth of neuropil and nonnervous elements. At the end of this three week period the cortical tissue and its neurons are apparently mature and the adult pattern of cortical fine structure is established.The purpose of this paper is to report the ultrastructural findings from a study of developing rat cerebral cortex between birth and three weeks of age and to the limited extent possible, to relate those findings to the light microscopic literature. However, a thorough review and consideration of the enormous literature on cortical histogenesis would not be feasible in a report such as this. Furthermore, there are inherent difficulties in relating electron microscopic studies to this literature. Classical methods of tissue preservation, paraffin embedment, metallic impregnation procedures and aniline stains fail to preserve or stain simultaneously all of the components of central nervous system tissues; and as a result, identification of cell types and interpretation of their relative development is difficult and largely subjective (Uzman, '60). By employing improvements in methods of tissue preservation that have paralleled the development of the electron mi-J. COMP. NEUR., 133: 17-44.croscope, especially in the use of osmium fixation and plastic embedment, there results a significantly different and improved image of developing cortex. It is interesting, however, that the microscopic images of the...