All migrating neuroblasts, which build up the neocor- tex PCP, attracted by reelin from Cajal–Retzius (C-R) cells and guided by radial glia fibers, must reach the first lamina. Upon reaching it, they lose the glia attachment and become pyramidal neurons with an
The Mammalian Pyramidal
Neuron: Development, Structure, and Function
4
apical dendrite that branches within the first lamina and establish functional contacts with C-R cells axon terminals (Marín-Padilla and Marín-Padilla 1982;
Marín-Padilla 1992, 1998). All pyramidal neurons of the neocortex are generated in the ependymal epithe- lium. In humans, the PCP formation starts around the 7th week of gestation and is nearly completed by the 15th week of gestation (w-g). The PCP neurons start their ascending and stratified functional maturation around the 15th week of gestation and will continue through both prenatal and early postnatal life (Chapter 3).
At 15-week gestation, the motor cortex PCP is a 100 cell thick plate extending throughout the entire neocortex, composed of tightly packed immature pyramidal neurons of various sizes, all functionally anchored to first lamina by their apical dendrite. At this age, no other neuronal types are recognized in the PCP. From this gestational age up to the time of birth and postnatally, the motor cortex pyramidal neurons mature anatomically and functionally, following an ascending sequential stratification, without losing their first lamina attachment and/or their body place- ment or cortical depth (Chapter 3).
The developmental requirement for all migrating neuroblasts of reaching the first lamina explains their inside–outside placement within the PCP. Any migrat- ing neuroblast must by-pass all preceding ones in order to reach the first lamina such that all preceding pyrami- dal neurons – to retain their original functional anchor- age to first lamina – must elongate “upwardly” their apical dendrite. Pyramidal neurons evolving from early arriving neuroblasts will occupy the PCP lower strata and will have the longest apical dendrites; while those arriving last will occupy the upper strata and will have shortest apical dendrites. The length of apical dendrites of pyramidal neurons located between the oldest and youngest ones will be intermediate. Consequently, the length of the apical dendrites denotes the arrival time of the pyramidal neuron at first lamina and its develop- mental age. Regardless of their morphological appear- ance, neurons that lose their functional attachment to first lamina (subplate neurons) and/or fail to develop them should not be considered as genuine pyramidal neurons (Marín-Padilla 1992).
The mammalian neocortex is composed of super- imposed and functionally interconnected pyramidal cell strata ranging from lower and older ones to super- ficial and younger ones. Therefore, the mammalian neocortex cytoarchitectural organization should be understood not as a descending (up–down) series of laminations (layers I, II, III, IV, V, and VI) as is por- trayed in the current nomenclature, but by a series of
Fig. 4.1 Montage of photomicrographs from rapid Golgi prepa- rations showing, comparatively, similar magnification, the size and functional maturation of a pyramidal neuron of P1 stratum (layer V of current nomenclature) from the motor cortex of a 15-week-old fetus (inset) and of a newborn infant. The extraor- dinary prenatal developmental morphological and functional maturation of this essential neuron of the human motor cortex has not been fully appreciated and/or recognized. The pyramidal cell size of the 15th-week-old fetus is 270 mm, has very short basal dendrites, and a couple of dendritic spines, while that of the newborn infant is 1,500 mm and all its dendrites are covered by spines. Only the rapid Golgi procedure is capable of demon- strating these neurons extraordinary, progressive, ascending, and stratified developmental morphological, and functional matura- tions (see Chapter 3)
37 4.1 Developmental Features
ascending stratified interconnected pyramidal cells (P1, P2, P3, P4, P5, and P6) functional strata. Both the current and the proposed developmental nomencla- tures are shown comparatively in some of the illustra- tions (Fig. 4.2a and Fig. 3.14).
From the start of development, any pyramidal neuron is locked into position between its func- tional anchorage to first lamina and the cortical depth (original placement) of its soma (Fig. 4.3).
Consequently, during their prenatal development, all pyramidal neurons must elongate “upwardly” their apical dendrite without losing either anchorage
(Fig. 4.3). During early development stages, all pyra- midal neurons elongate their apical dendrite anatom- ically to accommodate the subsequent incorporation, into the PCP, of additional ones. Later in develop- ment, all pyramidal neurons elongate their apical dendrites functionally (physiologically) by adding postsynaptic membrane to their main shaft, for the formation of dendritic spines and other types of syn- aptic contacts (Fig. 4.3, inset). This progressive functional elongation is also applicable to the neuron basal, collateral, and terminal dendrites within the first lamina (Fig. 4.3).
Fig. 4.2 Montage of camera lucida drawings and a photomicro- graph (c) from Golgi preparations showing, comparatively, the size, morphology, functional maturation, dendritic profiles, and the number of dendritic spines of P1 pyramidal neurons from the motor cortex of a newborn infant (a) and a 77-year-old man (b).
The insets (a) reproduce closer views of the neurons apical den- drites showing their variable morphology, number of dendritic spines, and some axo-spino-dendritic contacts with axon termi- nals. The old man’s pyramidal neuron (b) has thinner dendrites,
fewer dendritic branches, and a reduced number of dendritic spines, also some spines are structurally abnormal. Both the cur- rent (right) and the proposed (left) developmental nomenclature are shown comparatively (a). The rapid Golgi photomicrograph (c) represents a perpendicular section of a newborn motor cortex showing, a nearly complete P1 pyramidal neuron, at roughly the same magnification of those of the drawings for comparison.
Scale: 100 mm
Both types of developmental growths (elongations) invalidate a generally held idea, which proposes that apical dendrites of the pyramidal neurons grow up from cell body to the first lamina. Considering the extraordinary and increasing structural complexity of the neocortex, it is difficult to visualize the long apical dendrites of these neurons could grow (elongate) per- pendicular and so clean up to the pial surface, On the other hand, since all pyramidal neurons retain their original first lamina dendritic attachment, as the cortex thickness increases, all apical dendrites must elongate upward (Fig. 4.3). This new conception is applicable to all pyramidal neurons throughout the mammalian neocortex regardless of the size or location, including those within deep sulci and/or superficial gyri. It also
explains why even dendritic bifurcations (a common feature among large pyramidal neurons) are also per- pendicular to the pial surface (Figs. 4.1–4.3).