How the immense population of neurons that constitute the human cerebral neocortex is generated from progenitors lining the cerebral ventricle and then distributed to appropriate layers of distinctive cytoarchitectonic areas can be explained by the radial unit hypothesis. According to this hypothesis, the ependymal layer of the embryonic cerebral ventricle consists of proliferative units that provide a proto-map of prospective cytoarchitectonic areas. The output of the proliferative units is translated via glial guides to the expanding cortex in the form of ontogenetic columns, whose final number for each area can be modified through interaction with afferent input. Data obtained through various advanced neurobiological techniques, including electron microscopy, immunocytochemistry, [3H]thymidine and receptor autoradiography, retrovirus gene transfer, neural transplants, and surgical or genetic manipulation of cortical development, furnish new details about the kinetics of cell proliferation, their lineage relationships, and phenotypic expression that favor this hypothesis. The radial unit model provides a framework for understanding cerebral evolution, epigenetic regulation of the parcellation of cytoarchitectonic areas, and insight into the pathogenesis of certain cortical disorders in humans.

http://science.sciencemag.org/content/sci/241/4862/170.full.pdf

Specification of cerebral cortical areas

The development of stimulus selectivity in the primary sensory cortex of higher vertebrates is considered in a general mathematical framework. A synaptic evolution scheme of a new kind is proposed in which incoming patterns rather than converging afferents complete. The change in the efficacy of a given synapse depends not only on instantaneous pre- and postsynaptic activities but also on a slowly varying time-averaged value of the postsynaptic activity. Assuming an appropriate nonlinear form this dependence, development of selectivity is obtained under quite general conditions on the sensory environment. One does not require nonlinearity of the neuron's integrative power nor does one need to assume any particular form for intracortical circuitry. This is first illustrated in simple cases, e.g., when the environment consists of only two different stimuli presented alternately in a random manner. The following formal statement then holds: the state of the system converges with probability 1 to points of maximum selectivity in the state space. We next consider the problem of early development of orientation selectivity and binocular interaction in primary visual cortex. Giving the environment an appropriate form, we obtain orientation tuning curves and ocular dominance comparable to what is observed in normally reared adult cats or monkeys. Simulations with binocular input and various types of normal or altered environments show good agreement with the relevant experimental data. Experiments are suggested that could test our theory further.

/pdf/theory-for-the-development-of-neuron-selectivity-orientation-54wxhqbw54.pdf

Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex

Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histochemistry

Experience exerts a profound influence on the brain and, therefore, on behavior. When the effect of experience on the brain is particularly strong during a limited period in development, this period is referred to as a sensitive period. Such periods allow experience to instruct neural circuits to process or represent information in a way that is adaptive for the individual. When experience provides information that is essential for normal development and alters performance permanently, such sensitive periods are referred to as critical periods. Although sensitive periods are reflected in behavior, they are actually a property of neural circuits. Mechanisms of plasticity at the circuit level are discussed that have been shown to operate during sensitive periods. A hypothesis is proposed that experience during a sensitive period modifies the architecture of a circuit in fundamental ways, causing certain patterns of connectivity to become highly stable and, therefore, energetically preferred. Plasticity that occurs beyond the end of a sensitive period, which is substantial in many circuits, alters connectivity patterns within the architectural constraints established during the sensitive period. Preferences in a circuit that result from experience during sensitive periods are illustrated graphically as changes in a ''stability landscape,'' a metaphor that represents the relative contributions of genetic and experiential influences in shaping the information processing capabilities of a neural circuit. By understanding sensitive periods at the circuit level, as well as understanding the relationship between circuit properties and behavior, we gain a deeper insight into the critical role that experience plays in shaping the development of the brain and behavior.

https://faculty.washington.edu/losterho/knudson_critical_periods_jcn_2004.pdf

Sensitive Periods in the Development of the Brain and Behavior

The main purpose of this study was to examine the normal postnatal development of ocular dominance columns in the striate cortex of the macaque monkey and to determine how this developmental process is influenced by monocular lid-suture. The physiological pattern of ocular dominance was studied in long, tangential electrode penetrations. For anatomical demonstration of the distribution of afferents we relied principally on the transneuronal transport of [3H]proline injected into one eye, and to a lesser extent on the Liesegang silver method. The effects of deprivation on cell size in the lateral geniculate nucleus (LGN) were also studied. Twenty-six monkeys, divided into 5 groups (A–E), were used.



A
The process of normal columnar development was examined in four monkeys aged from 1 to 6 weeks. At one week, there was both an anatomical and a physiological mixing of left- and right-eye inputs to layer IVC, but the basic columnar pattern was evident, and some small regions were already monccular. At three weeks the columnar pattern resembled that seen in the adult, except for a suggestion that the borders between columns were not so sharply demarcated. By six weeks an adult degree of columnar segregation was established.

B
A series of ten monkeys had monocular suture performed at successively later ages, ranging from 2 days to adult, and they were allowed to survive for a long period. It was found that deprivation begun at any age from birth to about 6 weeks had approximately the same effect: the afferents for the open eye formed greatly expanded columns in layer IVC, and the columns for the closed eye were shrunken and fragmented. In the layers above and below IVC the open eye dominated almost completely. At 10 weeks, closure had only a mild effect on columnar size in layer IVC. With closures at 7–14 months there was no change in the size of columns in layer IVC, but when stained with the Liesegang silver method the deprived-eye columns were paler than those for the open eye, suggesting a lower density of fibers. These late deprivations still caused a shift of ocular dominance in the upper cortical layers but not such an extreme change as with earlier closures. Lid suture in an adult had no detectable anatomical or physiological effects. Even monocular enucleation, in an adult, failed to induce sprouting of the geniculocortical afferents for the remaining eye.

C
In order to investigate the rate at which monocular deprivation produces its effects, six monkeys were examined after short periods of deprivation in infancy. Eye-closure from birth to 3 weeks was sufficient to produce the full anatomical and physiological effects. A nine-day closure at 3 weeks, followed by reopening of the eye, also produced the full effects. A two-week period of deprivation begun at five weeks of age, however, caused relatively mild columnar expansion in layer IVC, suggesting that late closures may require more time to produce anatomical changes than early closures.

D
The effects of reopening the deprived eye and closing the experienced eye (reverse suture) were studied in three monkeys. The initial lid sutures were performed in the first few days of life. With reverse suture a t 3 weeks the relative sizes of the two sets of columns were reversed. This anatomical reversal was, however, limited to the afferents from the parvocellular laminae of the LGN; the magnocellular afferents remained in the pattern induced by the early deprivation. The layers outside of IVC were strongly dominated by the initially deprived eye. Reverse suture at 6 weeks allowed an anatomical recovery of the parvocellular afferents to a normal columnar size, but not a complete reversal. Again, the magnocellular afferents for the initially deprived eye were not induced t o enlarge their territory. Reverse suture at 1 year of age did not lead to any recovery.

E
One monkey was reared in complete darkness from 3 days of age until 7 weeks of age. This animal, studied autoradiographically, showed a normal columnar pattern in layer IVC.





We draw four conclusions from these experiments. (i) Ocular dominance columns are only partially formed a t birth but develop rapidly in the first few weeks of postnatal life. The process of segregation of the left- and right-eye afferents-in layer IV occurs in the presence or absence of visual experience. (ii) This developmental process may be redirected by early monocular deprivation, causing the segregation of the two sets of afferents into columns of unequal width, (iii) A rearrangement of the afferents can be induced for a short period after their segregation is complete. This is true of both normal and deprived animals. (iv) The eye preference of neurons in the upper and lower layers may be changed even after plasticity in layer-IVC is no longer detectable.

The development of ocular dominance columns in normal and visually deprived monkeys.

1. It was confirmed that suturing the lids of one eye (monocular deprivation), until only 5 weeks of age, leaves virtually every neurone in the kitten's visual cortex entirely dominated by the other eye. On the other hand, deprivation of both eyes causes no change in the normal ocular dominance of cortical neurones, most cells being clearly binocularly driven.

2. Kittens were monocularly deprived until various ages, from 5 to 14 weeks, at which time reverse suturing was performed: the initially deprived right eye was opened and the left eye closed for a further 9 weeks before recording from the visual cortex.

3. Reverse suturing at 5 weeks caused a complete switch in ocular dominance: every cell was dominated by the initially deprived right eye. Reverse suturing at 14 weeks, however, had almost no further effect on ocular dominance: most cells were still driven solely by the left eye. Animals reverse sutured at intermediate ages had cortical neurones strongly dominated by one eye or the other, and they were organized into clear columnar groups according to ocular dominance.

4. Thus, between 5 weeks and 4 months of age, there is a period of declining sensitivity to both the effects of an initial period of monocular deprivation and the reversal of those effects by reverse suturing.

5. The small proportion of binocular cells in reverse sutured kittens (which have never had simultaneous binocular vision) often differed considerably in their receptive field properties in the two eyes. In particular, if the cells were orientation selective in both eyes the two preferred orientations could differ by up to 70°.

6. The relative importance of innate and environmental contributions to the properties of cortical cells is discussed.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1974.sp010478

Reversal of the physiological effects of monocular deprivation in kittens: further evidence for a sensitive period.

The distribution of callosal cells and terminals was studied in the posterior neocortex of pups whose ages ranged from 3 to 16 days and in adult rats 2 months of age or older. Callosal cells and terminations were revealed using retrograde (horseradish peroxidase) and anterograde (horseradish peroxidase; tritiated proline) tracing techniques, respectively, and the distribution of callosal connections was analyzed in tangential or coronal histological sections. In agreement with previous studies, we observed that the pattern of callosal connections in areas 17 and 18 of adult rats contains the following features: (1) a dense band of callosal cells and terminations separating the interiors of areas 17 and 18a, (2) a ringlike configuration anterolateral to area 17, (3) a region of dense labeling lateral to area 18a, (4) several narrow bands of labeling that bridge area 18a at different anteroposterior levels, and (5) one or more labeled regions in area 18b. In all these callosal regions, labeled cells and terminations are densely aggregated in layers II-III, Va, and Vc-VIa, and less densely in layer IV and the remaining portions of layers V and VI. High densities of isotope-labeled fibers are also observed in the lower half of layer I. Throughout the interiors of areas 17 and 18a, a significant number of labeled cells are observed in layers Vc-VIa. In contrast to adult rats, in neonates no distinct tangential pattern of callosal connections is apparent. Instead, labeled cells are densely aggregated in two continuous horizontal bands located in cortical layers Va and Vc-VIa, and callosal axons are largely restricted to white matter. During the first 2 postnatal weeks there is a progressive loss of callosal cells in regions that normally have few callosal cells in the adult (e.g., interiors of areas 17 and 18a) and an increase in the number of cells in layers II-IV in regions that are densely callosal in the adult (e.g., callosal regions at the 17/18a border, lateral border of area 18a, and in area 18b). The decrease in the number of callosal cells in the interiors of areas 17 and 18a is more severe in the upper than in the lower band of the immature labeling pattern, and our data from tangential sections indicate that this loss of callosal neurons occurs synchronously across the interiors of these areas. During this period there is also a localized invasion of labeled callosal axons into those regions of gray matter where they will be found in adult life.(ABSTRACT TRUNCATED AT 400 WORDS)

Organization and postnatal development of callosal connections in the visual cortex of the rat.

Evidence for the complementary organization of callosal and thalamic connections within rat somatosensory cortex.

Following multiple injections of horseradish peroxidase into the posterior neocortex of one hemisphere, we examined the distribution of retrogradely labeled cells and anterogradely labeled terminations in tangential and coronal sections through contralateral areas 17 and 18 in throe groups of adult mice: normal-eyed (ZRDCT-n and C57Bl/6J strains), congenitally anophthalmic (ZRDCT-an strain), and neonatally enucleated (ZRDCT-n strain). In agreement with previous studies, we observed that the pattern of callosal connections in areas 17 and 18 of normal-eyed mice contains the following features: (1) a dense band of callosal cells and terminations separating the interiors of areas 17 and 18, which have relatively few callosal connections, (2) a ring-like configuration anterolateral to area 17, (3) a region of dense labeling lateral to area 18, (4) a narrow band of labeling bridging the posterior portion of area 18, and (5) a region of labeling anteromedial to area 17.



We find that all these features of the normal callosal pattern are recognizable in congenitally anophthalmic mice. Their presence in mice that never had eyes supports the hypothesis that central visual pathways can develop many aspects of their connectivity in the absence of input from the periphery. However, we also find that the details of certain features of the callosal pattern in congenitally eyeless mice often differ from those of the same features in normal-eyed mice, and that the between-animal variability in the appearance of these features is higher in eyeless mice. These latter findings indicate that the eyes are needed during normal development to fine-tune the pattern of callosal connections.



Our results also reveal that the callosal pattern in neonatally enucleated mice does not differ significantly from that in congenitally anophthalmic mice, indicating that the period in which the eyes guide callosal development extends into postnatal life. While the present data do not delineate the time course of this period, the finding of similarly abnormal callosal patterns in congentially anophthalmic and neonatally enucleated mice suggests that the eyes exert little if any influence prenatally. Finally, examination of coronal sections indicates that the laminar distribution of callosal connections develops normally in both groups of eyeless mice.

Richard C. Van Sluyters

Papers

Reversal of the physiological effects of monocular deprivation in kittens: further evidence for a sensitive period.

Organization and postnatal development of callosal connections in the visual cortex of the rat.

Evidence for the complementary organization of callosal and thalamic connections within rat somatosensory cortex.

Callosal connections of the posterior neocortex in normal-eyed, congenitally anophthalmic, and neonatally enucleated mice.

Widespread callosal connections in infragranular visual cortex of the rat.