Fig. 5.1 Montage of camera lucida drawings, from rapid Golgi preparations, showing the development of the human motor cor- tex first lamina cytoarchitectural organization and composition through the 11th, 16th, 20th, and 24th week of gestations. The first lamina essential neuronal and fiber composition changes very little during prenatal development. Early in development (A), the Cajal–Retzius (C-R) cells are large horizontal bipolar neurons sandwiched among the lamina numerous horizontal fiber terminals. Later in development (B, C), the C-R cells assume embryonic features characterized by the concentration of their dendritic and axonic processes into a reduced space and by their displacement toward the lamina upper region. By the 24-week gestation, C-R cells start to lengthen their processes, paralleling the cortex expansion, and start to assume more mature morphological features. The cortex first lamina is also
characterized by numerous horizontal fiber terminals, which expand its entire thickness, representing both C-R cell horizon- tal axonic collaterals and terminal axon and horizontal terminals from primordial corticipetal fibers. By the 20th–24th week of gestation (C, D) the lamina horizontal fiber terminals are segre- gated into those coursing through its upper region and those through its lower one. While C-R cells horizontal axon terminals tend to run through the lamina lower region, corticipetal fiber terminals run through its upper region coinciding with the neu- ron dendritic processes. Other first lamina components include the terminal dendritic bouquets of pyramidal neurons and the radial glia terminal filaments. Key: C-R at, C-R axon terminal;
G gl, glia; rg, radial glial fibers; a, afferent fibers; M, Martinotti axon terminals. Scales: 25 (A) and 100 mm (B, C, D)
The neocortex first lamina has also nonfunctional components, including innumerable radial glial fila- ments with terminal endfeet that, united by tight junc- tions, build, maintain, and repair the neocortex external glial limiting membrane (EGLM) and manufacture its basal lamina material (Figs. 5.1B, C and 5.2B, C). The
EGLM demarcates the neocortex (as well as the entire central nervous system) from surrounding meningeal tissues, maintains its anatomical and functional integ- rities and must be preserved intact throughout both prenatal and postnatal developments. Any EGLM rup- ture (mostly caused by pathological conditions) has to
Fig. 5.2 Montage of camera lucida drawings, from rapid Golgi preparations, showing the human motor cortex first lamina cyto- architectural and organization of fetuses of 29- (A) and 30-week of gestation (B) and of a newborn (C). The developmental lengthening “horizontalization” of C-R cells dendritic and axon terminals and primordial corticipetal fiber terminals has pro- gressed, paralleling the cortex expansion. Corticipetal fiber reached the lamina upper region and branch into long horizontal
terminals coinciding with the distribution of C-R cell dendrites.
The C-R cells descending axons give off numerous horizontal collaterals distributed throughout the lamina middle region and become long horizontal terminal (C-R at) throughout its lower region. Also illustrated are Martinotti cell (M) terminal axonic bouquets (B, C), some degenerating (dd) terminal dendrites (A).
Scales: 100mm
53 5.1 First Lamina Principal Components
be repaired. The EGLM reparation often resulted in the formation of leptomeningeal heterotopias, fre- quently associated with epilepsy (Marín-Padilla 1996, 1997, 1999, 2002). During prenatal development, the number of radial glia fibers increases progressively supplying the necessary additional glial endfeet for the EGLM of the expanding cortical surface. However, during later developmental stages, a special type of astrocytes becomes progressively incorporated into the first lamina contributing additional endfeet to the cor- tex expanding EGLM. Eventually, these first lamina special astrocytes will replace the radial glia as the main source of endfeet for the EGLM of the expanding neocortex (Chapter 8).
During late prenatal development, a variety of small local-circuit neurons are also incorporated into the first lamina. The local-circuit interneurons functional target is also the terminal dendritic bouquet of pyramidal neurons However, their anatomical and functional fields are restricted and localized and may vary from
region to region. Their local and restricted functional fields on the terminal dendrites of pyramidal neurons contrast sharply with the universal and shared func- tional field established by C-R cells long horizontal axonic terminals. The appearance, cytoarchitecture, and possible functional contributions of these late- incorporated secondary elements are explored below.
Eventually, growing capillaries from the pial anas- tomotic capillary plexus perforate the neocortex EGLM, enter into the neocortex, and progressively establish its extrinsic and intrinsic microvascular sys- tems (Chapter 7).
5.1 First Lamina Principal Components
From the start of development, C-R cells are recog- nized as large neurons sandwiched among corticipetal fibers with long horizontal processes, which tend to
Fig. 5.3 Composite figure with a camera lucida drawing (A) and a photomicrograph from a MAP2 dendritic stained prepara- tion (B) showing the large concentration of terminal dendritic bouquets of pyramidal neurons that characterized the mamma- lian cerebral cortex first lamina. The pyramidal terminal den-
drites represent the first lamina principal receptive system, which is functionally targeted by both corticipetal fiber terminals and C-R cell axon terminals. The light tubular structures seen in the middle of Fig. B represents a perforating capillary
occupy the lamina upper zone beneath the pial surface (Chapters 2 and 3). The first Golgi preparations of the human motor cortex available are from an 11-week- old fetus (Fig. 5.1A). At this stage, C-R cells are bipo- lar neurons with prominent horizontal dendrites and axonic terminals. No other neuronal types are recog- nized in the lamina at this stage. Other first lamina components include the long horizontal axonic termi- nals of primordial corticipetal fibers, the terminal den- dritic bouquets of SP zone pyramidal-like neurons, and those of newly incorporated pyramidal neurons (Fig. 5.1A). By the 15th week of gestation, the C-R cells have already assumed their distinctive morpho- logical appearance (Fig. 5.1B). They are large bipolar neurons with horizontal dendrites with numerous short ascending branches and a descending axon with hori- zontal collaterals that reaches the lower strata and becomes a long horizontal axonic terminal (Fig. 5.1B).
The concentration of dendritic processes closer to the neuron soma corresponds to its early or embryonic morphology. The neuron has not yet started its
progressive horizontal expansion and/or lengthening of its dendritic and axonic processes (Fig. 5.1B). The progressive lengthening of C-R cells processes is referred herein as: developmental “horizontalization.”
By the 20th week of gestation, the neocortex has expanded by the continued incorporation of additional dendritic bouquets of pyramidal neurons; consequently the C-R cells have started the progressive horizontal- ization of their dendritic and axonic processes (Fig. 5.1C). By the 24th week of gestation, the C-R cell dendritic and axonic processes horizontalization is at an intermediate stage and are recognized through- out the entire neocortex first lamina (Fig. 5.1D).
However, the recognition of the C-R cell neuron body, within a single Golgi preparation, decreases progres- sively. The actual number of C-R cells already estab- lished at the start of neocortical development will not increase further. Therefore, as the neocortex expands, these neurons undergo a progressive and significant developmental dilution. However, their long horizon- tal axonic processes are recognized throughout the
Fig. 5.4 Detailed camera lucida drawing, from Golgi prepara- tions, illustrating, at a higher magnification, the motor cortex first lamina essential functional system and its components. Afferent fiber terminals (AFT) reach and branch, throughout the lamina upper stratum, into long horizontal collaterals that coincide with C-R cells dendrites distribution and the terminal segments of den- drites of the pyramidal neurons. The C-R cell descending axon give off numerous horizontal collaterals (c) distributed through-
out the lamina middle stratum coinciding with the distribution of terminal dendrites of pyramidal cells. The C-R cell axon reaches the lamina lower stratum and becomes a long horizontal fiber (tangential fibers of Retzius). All the horizontal axonic terminals of corticipetal fibers, of C-R cells and the C-R cell terminal axons have numerous ascending and fewer descending branches distrib- uted among the terminal dendrites of pyramidal cells, suggesting both morphological as well as functional interrelationships
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