A transient pyramidal tract projection from the visual cortex in the hamster and its removal by selective collateral elimination

During the early postnatal development of the neocortex in rats there is an axonal projection from the occipital cortex (which includes the visual cortex) to the spinal cord which is subsequently completely removed through a process of selective collateral elimination. In order to determine whether a similar phenomenon occurs during the development of the hamster cortex, we have injected the retrogradely transported fluorescent dye Fast Blue (FB) into the pyramidal decussation of hamsters at various ages. In adult hamsters such an injection results in a band of labeled neurons confined to layer V and to about the rostral two-thirds of the neocortex; no labeled cells are seen in the occipital cortex. However, a similar FB injection made during the first postnatal week results after a 4-day survival in a continuous band of FB-labeled layer V neurons spread throughout the tangential extent of the neocortex, including the occipital cortex. A similar continuous band of FB labeled layer V neurons is seen throughout the tangential extent of the neocortex including the occipital region in hamsters injected during the first postnatal week but allowed to survive until the fourth week (i.e., after the restriction of the widespread neonatal pattern has occurred). Injections of the anterograde tracer wheat germ agglutinin conjugated to horseradish peroxidase made into the occipital cortex, or for comparison, into more rostral cortical regions in hamsters ranging in age from neonates to adults, reveal that the extension of pyramidal tract axons is staggered along the anterioposterior axis of the cortex such that axons originating from the posterior regions lag behind those arising from more rostral areas. The transient occipital projection appears to reach a maximum around the end of the first postnatal week: a large number of labeled occipital axons is seen in the medullary pyramidal tract, and some of these can be followed through the pyramidal decussation and into the dorsal funiculus of the spinal cord. Injections into the occipital cortex on P16 label only a few fibers in the medullary pyramidal tract, and none is labeled in hamsters injected as adults.(ABSTRACT TRUNCATED AT 400 WORDS)     

The physiological identification of pyramidal tract neurons within transplants in the rostral cortex taken from the occipital cortex during development

Axons from neurons in the occipital cortex transiently extend to the pyramidal tract (PT) during the early postnatal development of rats. Normally, these axons are eliminated by the end of the third postnatal week. However, if a portion of fetal occipital cortex is transplanted to the parietofrontal region in newborn hosts then some neurons in the transplant will extend pyramidal tract axons and maintain them. Intracortical microstimulation and electrophysiological recording techniques were used to identify the physiological characteristics of the transplanted pyramidal tract cells and to determine if motor effects could be elicited from the occipital transplant. Microstimulation of the transplant did not reliably evoke movement but the low density and disarray of PT cells within the transplant might account for this. Recording from within the transplant revealed that the overall cell activity was depressed. We were able to identify neurons within the transplant which responded antidromically to stimulation of the pyramidal tract, indicating that their axons have the capacity to conduct impulses and are therefore likely to have developed some viable connections. The functional significance of such projections remains uncertain.     

The transient corticospinal projection from the occipital cortex during the postnatal development of the rat

The transient occipital cortical component of the pyramidal tract which we previously had identified during the postnatal development of the rat (Stanfield et al., '82) has been studied with anterograde as well as retrograde techniques. A continuous band of retrogradely labeled layer V neurons which spans the entire cortex including the occipital cortex is seen following injections of the fluorescent marker Fast Blue into the pyramidal decussation during the first postnatal week. No labeled cells are found in the occipital cortex following similar injections made on postnatal day 20 (P20), although such injections label many neurons in the more rostral cortical fields. However, if the Fast Blue injection is made on P2 and the animal is allowed to survive until P25 a large number of Fast Blue-labeled layer V neurons is found in the occipital cortex, even though an acute, second injection of the retrograde tracer Nuclear Yellow made into the pyramidal decussation shortly before the animal is killed results in no occipital cortical labeling. When Fast Blue injections confined to the mid- or upper-cervical spinal cord are made on P4 and the animals are killed on P9, again many retrogradely labeled neurons are found in the occipital cortex. Further, when injections of 3H-proline or wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) confined to the occipital cortex are made during the first 2 postnatal weeks, anterogradely transported label is seen within the pyramidal tract. At all stages examined the amount of such label and its caudal extent are less than that seen following similar injections into the parietal or frontal cortex. The greatest extent of the labeled occipital cortical fibers is reached at about the end of the first postnatal week and the number of these fibers seems to peak at about this same time. At this stage many of these labeled axons extend for a considerable distance down the spinal cord with some reaching as far caudal as lower lumbar levels, and at this stage some of these labeled occipital corticospinal fibers enter into the spinal gray. Over the next week the number of occipital cortical fibers in the pyramidal tract rapidly decreases and by P17 occipital cortical injections of 3H-proline or WGA-HRP result in virtually no transported label caudal to the pons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Formation of an ipsilateral corticospinal tract after ablation of cerebral cortex in neonatal rat.

The formation of an aberrant ipsilateral corticospinal tract after unilateral cerebral cortical ablation during the neonatal period has been confirmed in the rat. The tract was chronologically studied using the antegrade horseradish peroxidase (HRP) tracing method. An aberrant ipsilateral tract is not observed 3 days after the operation. However, ipsilateral HRP positive fibers become apparent on day 7 and progressively more prominent until day 14. These results suggest that the ipsilateral corticospinal tract is composed of collateral axons originating from pyramidal neurons in the healthy ipsilateral cerebral cortex. These results also indicate that, when cerebral cortex has the damage during early postnatal life, the remaining cortical neurons which have been freed from the damage show considerable plasticity in terms of the collateral axons.     

Selective elimination of axons extended by developing cortical neurons is dependent on regional locale: experiments utilizing fetal cortical transplants

In adult rats, cortical neurons that extend an exon through the pyramidal tract (a major subcortical efferent projection of the neocortex) are limited to layer V of about the rostral two-thirds of the neocortex. In neonates, however, pyramidal tract neurons are distributed throughout the neocortex, but all of those found in certain areas, such as the posterior occipital region (including primary visual cortex) selectively lose their pyramidal tract axon (Stanfield et al., 1982) yet maintain axon collaterals to other subcortical targets (O'Leary and Stanfield, 1985). To determine if the regional location of a developing pyramidal tract neuron critically influences the maintenance or elimination of the axon collaterals it initially extends, pieces of cortex from embryonic day 17 (E17) rat fetuses (exposed to 3H-thymidine on E15) were transplanted heterotopically into the cortex of newborn (PO) rats; rostral cortex was placed into the posterior occipital region (R----O), or posterior occipital cortex into a rostral cortical locale (O----R). The retrograde tracers Fast blue (FB) and Diamidino yellow (DY) were used to assay for the presence of specific populations of cortical projection neurons within the autoradiographically identified transplants. In terms of the extension and maintenance of pyramidal tract axons, the transplanted neurons behave like the host neurons of the recipient cortical region rather than like those of their site of origin. At P40, following FB injections into the pyramidal decussation on P34, pyramidal tract neurons are labeled within the O----R transplants, but none can be labeled within R----O transplants, although in the same R----O cases transplanted neurons are labeled by an injection of DY in the superior colliculus. However, at P13 pyramidal tract neurons can be identified within the R----O transplants, as well as in the host occipital cortex, following injections made on P9, a period when the distribution of pyramidal tract neurons in normal rats is widespread (Stanfield and O'Leary, 1985b). In a second series of host rats, on P34 FB was injected in the pyramidal decussation of the O----R cases, or in the superior colliculus of the R----O cases, and in both groups DY was injected into the region of contralateral cortex homotopic for the new location of the transplant. On P40, in both the O----R and R----O transplants, many neurons singly labeled with FB or DY are found, but no double dye-labeled cells are seen.(ABSTRACT TRUNCATED AT 400 WORDS)     

Critical stages for growth in the development of cortical neurons

In order to study the role of efferent connectivity in the development of CNS neurons, the growth of pyramidal tract neurons within the hamster sensorimotor cortex was studied during normal development and after early postnatal lesions of the pyramidal tract. We first determined, by a combination of Nissl and retrograde HRP techniques, that within the lumbar representation of cortical layer 5B in adult animals two cell populations exist: a large-celled population (40% of the total) projecting to the spinal cord and a small-celled population (60% of the total) projecting intracortically and to targets rostral to the medulla. We could not determine whether large layer 5B cells in the infant sensorimotor cortex also represent the corticospinal population. Nevertheless, measurements of the growth in cross-sectional area of the large cells from 7 days postnatal to adulthood showed that these cells continue to grow until 51 days of age. The most rapid rate of growth occurs between 7 and 14 days, during which time the cross-sectional area of the cell bodies triples, coincident with the arrival of corticospinal axons in the lumbar cord and the beginning of target innervation (Reh and Kalil, '81). The growth of the large neurons in layer 5B was then charted after the pyramidal tract was cut ipsilaterally in the medulla at various postnatal ages. Early lesions of the tract (4-8 days postnatal) interrupt lumbar projection fibers before they establish synapses in the cord. Nevertheless, cortical cell bodies in the lumbar representation continue to grow normally after axotomy until 11 days after birth. At this time, large cells are arrested in development and their cell size remains in the 11-day stage (50% of normal adult large cell size) indefinitely. In contrast, adult lesions of the tract cause a 60% shrinkage of large cells, which in the adult represent corticospinal neurons. No evidence for cortical cell death was found after pyramidal tract lesions at any age. The results of axotomy reveal a turning point in the development of layer 5B cortical neurons. Before the age of 11 days the large cells have an independent program of cell growth that proceeds despite axotomy. After this time, the large cortical neurons appear to require intact axons for further growth and, in the absence of normal connectivity, are arrested in development.     

Specificity in the Development of Vertical Connections in Cat Striate Cortex

The main efferent axons of pyramidal cells in layer 2/3 in the adult cat striate cortex make collateral connections specifically within layer 2/3 and layer 5 and avoid the intervening layer 4. Intracellular dye injections in vitro were used to determine how, during early postnatal development, this precise pattern of laminar connections was achieved. These investigations revealed that the pattern of collateral outgrowth was specific from the very earliest time that axons began sprouting collaterals. During the first postnatal week, sprouts were seen exclusively within layers 2/3 and 5; no evidence for a transient connection to layer 4 was observed. Furthermore, collaterals emerged simultaneously within layers 2/3 and 5, despite the large difference in the postmigratory ages of the two layers. By the end of the second postnatal week, the adult number of collaterals was achieved. Further elaboration of the local arbors occurred by repeated branching of already existing collaterals, rather than by addition of new collaterals to the main axon. These results demonstrate that the formation of local connections between cortical layers is highly specific, in contrast to the development of clustered horizontal connections by these same cells within layers 2/3 and 5, which involves extensive remodelling of local connections.     

Development of inhibitory circuitry in visual and auditory cortex of postnatal ferrets: immunocytochemical localization of GABAergic neurons.

The goal of this study was to describe the development of gamma-aminobutyric acid (GABA)-containing neurons in visual and auditory cortex of ferrets. The laminar and tangential distribution of neurons containing excitatory, inhibitory, and neuromodulatory substances constrain the potential circuits which can form during development. Ferrets are born at an early stage of brain development, allowing examination of inhibitory circuit formation in cerebral cortex prior to thalamocortical ingrowth and cortical plate differentiation. Immunocytochemically labelled nonpyramidal GABA neurons were present from postnatal day 1 throughout development, in all cortical layers, and generally followed the inside-out pattern of neuronal migration into the cortical plate. Prior to postnatal day 14, pyramidal neurons with transient GABA immunoreactivity were also observed. The density of Nissl-stained and GABA-immunoreactive neurons was high early in development, declined markedly by postnatal day 20, then remained relatively constant until adulthood. However, examination of the proportion of GABA neurons revealed an unexpected late peak at postnatal day 60, then a decrease in adulthood. Visual and auditory cortex were similar in most respects, but the peak at postnatal day 60 and the final proportion of GABA neurons was higher in auditory cortex. The late peak suggests that inhibitory circuitry is stabilized relatively late in sensory cortical development, and thus that GABA neurons could provide an important substrate for experience-dependent plasticity at late stages of development.     

Dendritic morphology and axon collaterals of corticotectal, corticopontine, and callosal neurons in layer V of primary visual cortex of the hooded rat

Recent evidence indicates that corticotectal neurons belong to only one of the three morphological classes of pyramidal cells in layer V. The present study compares the dendritic morphology and axon collaterals of corticotectal, corticopontine, and layer V callosal neurons by using techniques based on the retrograde transport of horseradish peroxidase and fluorescent dyes as well as in vitro intracellular dye injections. Our results indicate that corticotectal and corticopontine neurons are located predominantly in the upper middle part of layer V. These neurons have medium to large somas with 5 or 6 primary basal dendrites and a single apical dendrite ascending to layer I. Approximately 60% of these cells send axon collaterals to both the superior colliculus and the pons. In contrast, callosal neurons form a heterogeneous group. In general, they have small pyramidal or ovoid cell bodies which give rise to 3 or 4 primary basal dendrites. Many cells have an apical dendrite that bifurcates and terminates in layer V or IV. We find that callosal neurons do not send an axon collateral to either the superior colliculus or the pons. We conclude that the corticotectal and corticopontine systems are similar in their intralaminar distribution, dendritic morphology, and pattern of axon collaterals, whereas the callosal system differs in these characteristics.     

Functional classes of cortical projection neurons develop dendritic distinctions by class-specific sculpting of an early common pattern.

We demonstrate in rat neocortex that the distinct laminar arrangements of the apical dendrites of two classes of layer 5 projection neurons, callosal and corticotectal, do not arise de novo, but are generated later in development from a common tall pyramidal morphology. Neurons of each class initially elaborate an apical dendrite in layer 1. Layer 5 callosal neurons later lose the segments of their apical dendrite superficial to layer 4, generating their characteristic short pyramidal morphology. The apical dendrite of layer 5 callosal neurons later lose the segments of their apical dendrite superficial to layer 4, generating their characteristic short pyramidal morphology. The apical dendrite of layer 5 callosal neurons is actively eliminated, rather than passively displaced, as superficial cortical layers expand. Corticotectal neurons and callosal neurons superficial to layer 5 maintain their apical dendrite to layer 1. Therefore, this selective dendritic loss occurs in a neuron class-specific manner and, within the callosal population, in a lamina-specific manner. Based on our additional observations and other studies, this phenomenon can be extended to other types of cortical projection neurons. These findings show that selective dendritic elimination plays a major role in shaping the functional architecture characteristic of the adult cortex.     

Development of specificity in corticospinal connections by axon collaterals branching selectively into appropriate spinal targets

Corticospinal projections in adult rodents arise exlusively from layer V neurons in the sensorimotor cortex. These neurons are topographically organized in their connections to spinal cord targets. Previous studies in rodents have shown that the mature distribution pattern of corticospinal neurons develops during the first 2 weeks postnatal from an initial widespread pattern that includes the visual cortex to a distribution restricted to the sensorimotor cortex. To determine whether specificity in corticospinal connections also emerges from an intially diffuse set of projections, we have studied the outgrowth of corticospinal axons and the formation of terminal arbors in developing hamsters. The sensitive fluorescent tracer 1, 1′, dioctadecyl-3, 3, 3′, 3′-tetramethylindocarbocyanine perchlorat (DiI) was used to label corticospinal axons from the visual cortex or from small regions of the forelimb or hindlimb sensorimotor cortex in living animals at 4–17 days postnatal. Initially axon outgrowth was imprecise. Some visual cortical axons extended transiently beyond their permanent targets in the pontine nuclei, by growing through the pyramidal decussation and in some cases extending as far caudally as the lumbar enlargement. Forelimb sensorimotor axons also extended past their targets in the cervical enlargement, in many cases growing in the corticospinal tract to lumbar levels of the cord. By about 17 days postnatal these misdirected axons or axon segments were withdrawn from the tract. Despite these errors in axon trajectories within the corticospinal tract, terminal arbors branching into targets in the spinal gray matter were topographically appropriate from the earliest stages of innervation. Thus visula cortical axons never formed connections in the spinal cord, forelimb sensorimotor axons arborized only in the cervical enlargement, and hindlimb cortical axons terminated only in the lumbar cord at all stages of development examined. Corticospinal arbors formed from collaterals that extended at right angles from the shafts of primary axons, most likely by the process of interstitial branching after the primary growth cone had extended past the target. Once collaterals extended into the spinal gray matter, highly branched terminal arbors formed within 2–4 days, beginning at about 4 and 8 days postnatal for the cervical and lumbar enlargements, respectively. These results show that specificity in connectivity is achieved by selectivty growth of axon collaterals in to appropriate spinal targets from the beginning and not by the later remodeling of intially diffuse connections. In contrast, errors occur in the initial outgrowth of axons in the corticospinal tract, which are subsequently corrected. Copyright © 1994 Wiley-Liss, Inc.     

The postnatal development of corticotrigeminal projections in the cat

The postnatal development of corticotrigeminal projections was studied in kittens following 3H-amino acid injections into the face area of the primary somatosensory cortex. Corticofugal axons grow into the brainstem and form the pyramidal tract prenatally. Corticotrigeminal projections begin to develop at the end of the first postnatal week. The earliest corticotrigeminal axons grow out of the pyramidal tract caudally and project into laminae III-V of the spinal trigeminal (Vs) nucleus caudalis. During the second postnatal week, corticotrigeminal axons grow out of the pyramidal tract in a caudal to rostral sequence and project up to the ventromedial borders of Vs-interpolaris, Vs-oralis, and to the principal trigeminal nucleus. Corticotrigeminal axons pause at the periphery of these nuclei for 1-2 days before penetrating the trigeminal neuropil and forming terminal arborizations in a centripetal direction. Coincident with the development of cortical projections to the principal trigeminal nucleus, some of the labeled axons which were in lamina III of Vs-caudalis project into lamina I and terminate. This sequence of development of corticotrigeminal projections closely parallels, albeit at a later time, the sequence of formation of the trigeminal nuclei, suggesting that the temporal sequence of cytogenesis of trigeminal neurons may be a factor which regulates their order of innervation by afferents. Corticotrigeminal projections develop bilaterally and, during the second postnatal week, are relatively equal in density in the ipsilateral and contralateral nuclei. Many of the ipsilateral corticotrigeminal projections are lost, however, after the second postnatal week, so that by the fourth postnatal week, corticotrigeminal projections are mainly contralateral and adultlike in their distribution. It remains to be determined whether the transience of ipsilateral corticotrigeminal projections is due to selective elimination of axon collaterals or to neuronal death.     

Transient cortical pathways in the pyramidal tract of the neonatal ferret

Anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was used to study transient axons from the visual cortex in the pyramidal tract. Injections at birth restricted to the visual cortex labeled axons in the vicinity of the pontine nuclei. Two to eight days after birth, axons from the occipital cortex were found posterior to the pontine nucleus, their caudalmost stable target. Transient corticospinal axons from the presumptive primary visual cortex did not grow caudal to the pyramidal decussation. Innervation of more distal targets preceded innervation of proximal targets. Innervation of the pontine nucleus is initiated around 68 hours after birth, when the transient extension in the medullary pyramidal tract has attained its maximum caudal extent. Innervation of the superior colliculus begins 9 days after birth. Retrograde tracers were used to follow the developmental changes in the cortical distribution of the parent neurons giving rise to axons in the pyramidal tract. In the adult, labeled neurons following injection of retrograde tracer in the pyramidal tract occupied less than a third of the neocortex and were centred on the anterior part of the coronal and spleniocruciate gyri. In the immature brain, labeled neurons covered more than two-thirds of the neocortex. Areal density measurements in the neonate showed that peak labeling was centred in the anterior coronal and spleniocruciate gyri, where corticospinal cells in the adult are located. There was a marked rostral-caudal gradient so that labeled neurons were very scarce towards the occipital pole. These results, showing transient neocortical axons in the pyramidal tract in a carnivore, suggest that this may be a common feature of mammalian development. The finding that the adult pattern of corticospinal projections does not emerge from a uniform distribution is discussed with respect to the areal specification of cortical connectivity. © 1993 Wiley-Liss, Inc.     

Expression of CRYM in different rat organs during development and its decreased expression in degenerating pyramidal tracts in amyotrophic lateral sclerosis

The protein μ‐crystallin (CRYM) is a novel component of the marsupial lens that has two functions: it is a key regulator of thyroid hormone transportation and a reductase of sulfur‐containing cyclic ketimines. In this study, we examined changes of the expression pattern of CRYM in different rat organs during development using immunohistochemistry and immunoblotting. As CRYM is reportedly expressed in the corticospinal tract, we also investigated CRYM expression in human cases of amyotrophic lateral sclerosis (ALS) using immunohistochemistry. In the rat brain, CRYM was expressed in the cerebral cortex, basal ganglia, hippocampus and corticospinal tract in the early postnatal period. As postnatal development progressed, CRYM expression was restricted to large pyramidal neurons in layers V and VI of the cerebral cortex and pyramidal cells in the deep layer of CA1 in the hippocampus. Even within the same regions, CRYM‐positive and negative neurons were distributed in a mosaic pattern. In the kidney, CRYM was expressed in epithelial cells of the proximal tubule and mesenchymal cells of the medulla in the early postnatal period; however, CRYM expression in the medulla was lost as mesenchymal cell numbers decreased with the rapid growth of the medulla. In human ALS brains, we observed marked loss of CRYM in the corticospinal tract, especially distally. Our results suggest that CRYM may play roles in development of cortical and hippocampal pyramidal cells in the early postnatal period, and in the later period, performs cell‐specific functions in selected neuronal populations. In the kidney, CRYM may play roles in maturation of renal function. The expression patterns of CRYM may reflect significance of its interactions with T3 or ketimines in these cells and organs. The results also indicate that CRYM may be used as a marker of axonal degeneration in the corticospinal tract.     

The transience of cerebrocerebellar projections is due to selective elimination of axon collaterals and not neuronal death

Fluorescent dyes were used to determine firstly if the transience of cerebrocerebellar projections in neonatal kittens is due to the selective elimination of axon collaterals or to neuronal death; and secondly, if the cerebrocerebellar projection neurons lived, did any maintain a projection to the brainstem or spinal cord. Injections of Fast Blue were made into the cerebellar cortex and deep nuclei in 7-9 postnatal days old kittens, the age in which cortical axons grow into the cerebellum. Later, at 31-71 postnatal days of age, when the transient cerebrocerebellar projections have disappeared, injections of Nuclear Yellow were made into the brainstem or the spinal cord. In the frontoparietal cortex, numerous neurons were labeled with Fast Blue suggesting that the disappearance of cerebrocerebellar projections is due primarily to the selective elimination of axon collaterals and not neuronal death. Moreover, many of the cortical neurons labeled with Fast Blue also were labeled with Nuclear Yellow which shows that many of the cortical neurons with transient collateral projections to the cerebellum in the neonate maintain a projection to brainstem or spinal targets in older animals.     

Laminar and areal differences in the origin of the subcortical projection neurons of the rat somatosensory cortex

Fluorescent retrograde tracing techniques were employed in a double-labelling paradigm to determine the distribution of corticospinal, corticotectal, and corticotrigeminal projection neurons in layer Vb of the adult and neonatal rat somatosensory cortex. The double-labelling paradigm allowed a direct comparison of the cortical distribution of neurons projecting to each target and identification of neurons projecting to more than one target. In the adult rat, each population of projection neurons was found to have a unique laminar and/or areal distribution. Corticospinal projection neurons were located throughout the width of layer Vb in the medial granular portion of somatosensory cortex, while corticotrigeminal projection neurons were distributed throughout the width of layer Vb in the more laterally located dysgranular portion of somatosensory cortex. Corticotectal projection neurons were located more superficially in layer Vb than either corticospinal or corticotrigeminal projection neurons and found scattered throughout both dysgranular and granular somatosensory cortex. Each combination of subcortical injections also resulted in double labelling a small percentage of uniquely distributed neurons. These distribution differences coupled with measurements of cell size allowed us to identify the parent population of the dual projection neurons. Subpopulations of corticotectal neurons also project to the brainstem trigeminal complex and to the spinal cord. Subpopulations of corticotrigeminal neurons also project to the spinal cord, and a proportion of corticotrigeminal neurons projects to at least two targets within the brainstem trigeminal complex (nucleus principalis and subnucleus interpolaris). In the adult rat, corticospinal neurons (as defined by either laminar position or somal size) did not appear to give off collaterals to either the superior colliculus or brainstem trigeminal complex. In the neonatal rat, double-labelled neurons which project to both the spinal cord and the tectum are distributed throughout the full width of layer Vb, rather than restricted to the superficial portion of the layer as in the adult rat. Further, it appears as if the ontogenetic change in the laminar distribution of corticospinal and tectal projection neurons is achieved by mechanisms of selective process elimination rather than cell death. These results are discussed in terms of both the developmental factor which may contribute to the discrete distribution of cortical projection neurons found in the adult and the functional significance of bifurcating projection neurons.     

Transplantation of embryonic occipital cortex to the brain of newborn rats: a Golgi study of mature and developing transplants

Segments of the occipital cortex were taken from rat embryos (E16-E19) and transplanted to the cerebral cortex or the tectal region of a newborn rat host. With the aid of Golgi impregnation techniques, neuron morphology was studied in cortical transplants which had survived for 1 week or more in the host brain. In mature transplants (greater than 4 weeks) three main groups of neurons, termed groups I-III, were identified. Group I neurons resembled pyramidal neurons of the intact cerebral cortex. No preferential orientation of either soma or dendrites of group I neurons was observed in the transplants, and some group I neurons had curved apical dendrites. Group II neurons had predominantly stellate form and their dendrites were densely covered with spines. Paucity or absence of dendritic spines characterized group III neurons which exhibited various dendritic topologies. Different neuron types were also recognized in immature transplants growing for 1 and 2 weeks in the host brain. The sequence of dendritic maturation of transplanted cortical neurons is similar to that seen in intact cortex, although the stage reached related more to the actual age of the transplant than to that of the host. Thus, group I neurons in the 1-week-old transplants taken from E16 embryos had not attained the same complexity of branching as pyramidal neurons in the surrounding host cortex, but rather resembled slightly younger cells more like those found in the cerebral cortex of the newborn rat. These results show, therefore, that at least the basic cell classes identified in intact visual cortex can also be recognized in the cortical transplants. This will provide a foundation for studies defining which cells project to the host brain and which are involved in particular intrinsic connections.     

The development of the corticotectal pathway in the albino rat

To study the development of the corticotectal pathway, the enzyme horseradish peroxidase (HRP) was injected electrophoretically into the superior colliculus (SC) of rats ranging in age from newborn to adult. In animals younger than postnatal day 3 (P3), collicular injections did not label any cells in the cortex while in animals injected at P3-P4, only a few cortical cells were retrogradely labeled. In contrast, injections made at P5 or later resulted in the labeling of a substantial proportion of lamina V cells in a number of cortical areas ipsilateral to the injected colliculus. Although at P5-P7 the bulk of labeled cells was located in the visual cortices (both striate and extrastriate), a substantial proportion of the labeled cells was located in the somatosensory, motor and association cortices. On the other hand, in animals injected at P12 (or later), the labeled cells were largely restricted to the visual cortices with relatively few corticotectal cells located in somatosensory area I. At all ages studied, labeled cortical cells were confined to lamina V and had clear-cut apical dendrites (pyramidal cells). The dendritic morphologies and somal sizes of the corticotectal cells indicate that in animals younger than P12 these cells are immature. These observations suggest that the axons of cortical cells do not reach the SC before P3 and that these early corticotectal projections (P3-P12) are established by immature cells. Furthermore, although the corticotectal projection exhibits, from its onset, a high degree of specificity in terms of the laminar distribution of its cells of origin, its areal distribution is 'exuberant'. The 'exuberant' projections originating from non-visual cortical areas disappear by P12-P14, that is at the time when young rats open their eyes for the first time.     

Prenatal development of neurons in the human prefrontal cortex. II. A quantitative Golgi study.

The quantitative development of neurons in the human dorsolateral and lateral prefrontal cortex was studied in Golgi-impregnated tissue from postmortem brains ranging from 13.5 weeks of gestation up to the second postnatal month. Pyramidal neurons in the future layers III and V of the cortical plate, as well as different types of neurons in the transient subplate zone, were studied. The basal dendrites of the future layer III and V pyramidal neurons show a slow increase during the first two-thirds of the period of gestation. From 27-32 weeks of gestation on, there is a rapid increase in the length of basal dendrites of layer III and V pyramidal neurons, while the number of basal dendrites per pyramidal neuron appears to stabilize at 26/27 weeks of gestation. The increase in total length of basal dendrites per pyramidal neuron is mainly due to an increase in the number of bifurcations and the growth of terminal segments. Throughout the whole period studied, the size of the layer III pyramidal basal dendritic tree was smaller than that of layer V pyramidal neurons. Thus, not until postnatal life do the layer III pyramidal basal dendrites become larger than those of layer V. No statistically significant differences were found for data of the pyramidal neurons between the superior and middle frontal gyri. The dendritic size of subplate neurons, except for the subplate inverted pyramidal neurons, significantly exceeds the size of the basal dendrites of the pyramidal neurons up to the seventh gestational month, which indicates an earlier maturation of these subplate neurons. During the period examined, no clear decrease in the size of the subplate neurons was observed. The present study shows that the dendritic parameters of either subplate or cortical plate pyramidal neurons rapidly increase during the periods of ingrowth of afferent fibers into the subplate zone and cortical plate, respectively. In the Golgi preparations of the prefrontal cortex, the size of the subplate neurons does not show any clearly regressive changes at the end of the prenatal period.