Fluoxetine and serotonin facilitate attractive‐adaptation‐induced orientation plasticity in adult cat visual cortex

Neurons in V1 display orientation selectivity by responding optimally to a preferred orientation edge when it is presented within their receptive fields. Orientation plasticity in striate cortex occurs either by ocular deprivation or by imposition of a non‐preferred stimulus for several minutes. Adaptation of neurons to a non‐optimal orientation induces shifts of tuning curves towards the adapting orientation (attractive shift) or away from it (repulsive shift). Here, we investigated the effects of the neurotransmitter serotonin and antidepressant fluoxetine (a selective serotonin reuptake inhibitor) on the modulation of adaptation‐induced orientation plasticity. We show that serotonin and fluoxetine promote mostly attractive shifts. Attractive shifts augmented in magnitude towards adapter, whereas repulsive neurons reversed their behavior in the direction of the forced orientation. Furthermore, neurons which retained their original preferred orientation expressed plasticity by shifting their tuning curves after drug administration mostly towards adapter. Our data suggest a pre‐eminent role of fluoxetine by inducing and facilitating short‐term plasticity in V1.     

Comparative analysis of orientation maps in areas 17 and 18 of the cat primary visual cortex following adaptation

Object orientations in the visual field are columned into specific orientation domains in the primary visual cortex [area 17 (A17) and area 18 (A18)] of cats. At the single‐cell level, adapting A17 neurons to a non‐preferred orientation (adaptor) shifts their preferred orientation either towards the adaptor (attractive shift) or away from it (repulsive shift). As A17 and A18 are reciprocally connected, we sought to determine how changes in preferred orientations in A18 neurons are correlated with changes recorded in A17 anesthetised cats. To this end, we simultaneously traced populations of neurons in A17 and A18, using intrinsic optical imaging, before and after long (12 min) and short (3 min) adaptations. The comparison of A17 and A18 maps pre‐adaptation and post‐adaptation showed that variance in shift amplitudes is greater in A18 than A17 for short adaptations. Our results indicate a rapid reconfiguration of functional maps that may spread to many cortical areas.     

Spatio-temporal prediction and inference by V1 neurons

In normal vision, visual scenes are predictable, as they are both spatially and temporally redundant. Evidence suggests that the visual system may use the spatio-temporal regularities of the external world, available in the retinal signal, to extract information from the visual environment and better reconstruct current and future stimuli. We studied this by recording neuronal responses of primary visual cortex (area V1) in anaesthetized and paralysed macaques during the presentation of dynamic sequences of bars, in which spatio-temporal regularities and local information were independently manipulated. Most V1 neurons were significantly modulated by events prior to and distant from stimulation of their classical receptive fields (CRFs); many were more strongly tuned to prior and distant events than they were to CRFs bars; and several showed tuning to prior information without any CRF stimulation. Hence, V1 neurons do not simply analyse local contours, but impute local features to the visual world, on the basis of prior knowledge of a visual world in which useful information can be distributed widely in space and time.     

Comparative pharmacological effects on visual cortical neurons in monocularly deprived cats

Monocularly deprived (MD) cats show a loss of responsiveness to visual stimulation of the deprived eye among visual cortical neurons. Several lines of evidence suggest that this effect involves, at least in part, a suppression of deprived eye input, possibly mediated by GABA inhibition. In order to better understand the nature of this suppression we have evaluated the effectiveness of different types of disinhibitory and excitatory agents to reverse the effects of MD. We investigated bicuculline (a GABA antagonist); picrotoxin (a GABA antagonist with a different mechanism of action from bicuculline); strychnine (a glycine antagonist); ammonium ion (a blocker of membrane chloride channels); physostigmine (a cholinesterase inhibitor); and naloxone (an opiate antagonist and also a GABA antagonist). All drugs were given intravenously. Bicuculline restored binocularity to 50% of the visual cortical neurons tested and naloxone to 36%. With both drugs, receptive fields of the normal eye tended to lose specificity. The emergent deprived eye receptive fields were usually similar to those of the normal eye after drug administration. Ammonium ion produced binocular responses in 27% of neurons tested, but receptive fields were grossly abnormal; moreover, ammonium infusion tended to depress neuronal responsiveness. All other drugs tested failed to restore binocularity. These experiments lend further credence to the hypothesis that GABA inhibition contributes to the cortical effects of MD, since only drugs with GABA antagonistic action were effective in restoring neuronal responsiveness to the deprived eye.     

The V1–V2–V3 complex: quasiconformal dipole maps in primate striate and extra-striate cortex

The mapping function w=k log(z+a) is a widely accepted approximation to the topographic structure of primate V1 foveal and parafoveal regions. A better model, at the cost of an additional parameter, captures the full field topographic map in terms of the dipole map function w=k log[(z+a)/(z+b)]. However, neither model describes topographic shear since they are both explicitly complex-analytic or conformal. In this paper, we adopt a simple ansatz for topographic shear in V1, V2, and V3 that assumes that cortical topographic shear is rotational, i.e. a compression along iso-eccentricity contours. We model the constant rotational shear with a quasiconformal mapping, the wedge mapping. Composing this wedge mapping with the dipole mapping provides an approximation to V1, V2, and V3 topographic structure, effectively unifying all three areas into a single V1–V2–V3 complex using five independent parameters. This work represents the first full-field, multi-area, quasiconformal model of striate and extra-striate topographic map structure.     

Neurochemical gradients along monkey sensory cortical pathways: calbindin-immunoreactive pyramidal neurons in layers II and III

We examined the distribution of neurons containing immunoreactivity for three calcium-binding proteins, calbindin, parvalbumin and calretinin, as well as nonphosphorylated neurofilament protein, in cortical areas along the ventral and dorsal cortical visual pathways, and in ventrally-directed somatosensory and auditory cortical pathways. Calbindin-immunoreactive pyramidal neurons showed the most prominent regional differences. They were largely restricted to layers II and III and their number monotonically increased from the primary sensory areas to the anteroventral areas along the ventral visual pathway and along the ventrally-directed somatosensory and auditory pathways. The number of calbindin-immunoreactive pyramidal neurons in layers II and III also increased along the dorsal visual pathway, but the number in the last recognized stage of the dorsal visual pathway (area 7a) was significantly smaller than that at the corresponding stage in the ventral visual pathway (TE). The number of calbindin-immunoreactive pyramidal neurons was highest in layers II and III of areas 35/36, TG, and TF/TH, which represent terminal cortical regions of the pathways. These results show neurochemical differences between cortical areas located at early and late stages along serial corticocortical pathways, as well as confirming differences between pyramidal neurons in the supragranular and infragranular layers.     

Cross‐modal reorganization of cortical afferents to dorsal auditory cortex following early‐ and late‐onset deafness

Cat auditory cortex is known to undergo cross‐modal reorganization following deafness, such that behavioral advantages in visual motion detection are abolished when a specific region of deaf auditory cortex, the dorsal zone (DZ), is deactivated. The purpose of the present investigation was to examine the connectional adaptations that might subserve this plasticity. We deposited biotinylated dextran amine (BDA; 3,000 MW), a retrograde tracer, unilaterally into the posterior portion of the suprasylvian fringe, corresponding to area DZ of hearing, early‐deafened (onset <1 month), and late‐deafened (onset >3 months) cats to reveal cortical afferent projections. Overall, the pattern of cortical projections to DZ was similar in both hearing and deafened animals. However, there was a progressive increase in projection strength among hearing and late‐ and early‐deafened cats from an extrastriate visual cortical region known to be involved in the processing of visual motion, the posterolateral lateral suprasylvian area (PLLS). Additionally, although no such change was documented for the posteromedial lateral suprasylvian area (PMLS), labeled neurons were present within a subregion of PMLS devoted to foveal vision in both late‐ and early‐deafened animals but not in hearing controls. PMLS is also an extrastriate visual motion processing area and is widely considered to be the homolog of primate middle temporal area. No changes in auditory cortical connectivity were observed among groups. These observations suggest that amplified cortical projections from extrastriate visual areas involved in visual motion processing to DZ may contribute to the cross‐modal reorganization that functionally manifests as superior visual motion detection ability in the deaf animal. J. Comp. Neurol. 522:654–675, 2014. © 2013 Wiley Periodicals, Inc.     

Receptive‐field properties of V1 and V2 neurons in mice and macaque monkeys

We report the results of extracellular single‐unit recording experiments where we quantitatively analyzed the receptive‐field (RF) properties of neurons in V1 and an adjacent extrastriate visual area (V2L) of anesthetized mice with emphasis on the RF center‐surround organization. We compared the results with the RF center‐surround organization of V1 and V2 neurons in macaque monkeys. If species differences in spatial scale are taken into consideration, mouse V1 and V2L neurons had remarkably fine stimulus selectivity, and the majority of response properties in V2L were not different from those in V1. The RF center‐surround organization of mouse V1 neurons was qualitatively similar to that for macaque monkeys (i.e., the RF center is surrounded by extended suppressive regions). However, unlike in monkey V2, a significant proportion of cortical neurons, largely complex cells in V2L, did not exhibit quantifiable RF surround suppression. Simple cells had smaller RF centers than complex cells, and the prevalence and strength of surround suppression were greater in simple cells than in complex cells. These findings, particularly on the RF center‐surround organization of visual cortical neurons, give new insights into the principles governing cortical circuits in the mouse visual cortex and should provide further impetus for the use of mice in studies on the genetic and molecular basis of RF development and synaptic plasticity. J. Comp. Neurol. 518:2051–2070, 2010. © 2010 Wiley‐Liss, Inc.     

The effects of LSD and some analogues on the responses of single cortical neurons of the cat to optical stimulation

The effects of lysergic acid diethylamide (LSD) and its analogues, 2-bromo-LSD (BOL) and methysergide, have been investigated on the responses to photic stimulation of single neurons in the striate cortex of the paralyzed, anesthetized cat. Systemic LSD (0.1--50 micrograms/kg, i.v.) produced: (a) enhancement or depression of evoked activity, the former being common with low, the latter with high doses; (b) changes in directional selectivity; and (c) changes in unstimulated background discharges. The effectiveness of the drug was reduced by repeated administration. Both BOL (10--75 micrograms/kg) and methysergide (100-700 micrograms/kg) produced effects qualitatively similar to LSD, but were considerably less potent. Microelectrophoretic administrations of LSD to single cortical neurons had actions similar to those caused by intravenous administration. BOL and methysergide required much larger currents to produce any effect and sometimes no effect could be induced by iontophoresis. It was concluded that these drugs influence visually evoked neuronal responses mainly by acting directly on cortical cells or synapses; and that the interference with visual cortical function could account for the distortion of visual perception caused by lysergic acid analogues; but that the hallucinogenic and psychotomimetic actions of LSD probably require additional subcortical effects.     

Indirect pathway between the primary auditory and visual cortices through layer V pyramidal neurons in V2L in mouse and the effects of bilateral enucleation

Visual cortical areas are activated by auditory stimuli in blind mice. Direct heteromodal cortical connections have been shown between the primary auditory cortex (A1) and primary visual cortex (V1), and between A1 and secondary visual cortex (V2). Auditory afferents to V2 terminate in close proximity to neurons that project to V1, and potentially constitute an effective indirect pathway between A1 and V1. In this study, we injected a retrograde adenoviral vector that expresses enhanced green fluorescent protein under a synapsin promotor in V1 and biotinylated dextran amine as an anterograde tracer in A1 to determine: (i) whether A1 axon terminals establish synaptic contacts onto the lateral part of V2 (V2L) neurons that project to V1; and (ii) if this indirect cortical pathway is altered by a neonatal enucleation in mice. Complete dendritic arbors of layer V pyramidal neurons were reconstructed in 3D, and putative contacts between pre-synaptic auditory inputs and postsynaptic visual neurons were analysed using a laser-scanning confocal microscope. Putative synaptic contacts were classified as high-confidence and low-confidence contacts, and charted onto dendritic trees. As all reconstructed layer V pyramidal neurons received auditory inputs by these criteria, we conclude that V2L acts as an important relay between A1 and V1. Auditory inputs are preferentially located onto lower branch order dendrites in enucleated mice. Also, V2L neurons are subject to morphological reorganizations in both apical and basal dendrites after the loss of vision. The A1-V2L-V1 pathway could be involved in multisensory processing and contribute to the auditory activation of the occipital cortex in the blind rodent.     

Comparison of spatial integration and surround suppression characteristics in spiking activity and the local field potential in macaque V1

Neurons in primary visual cortex exhibit well documented centre–surround receptive field organization, whereby the centre is dominated by excitatory influences and the surround is generally dominated by inhibitory influences. These effects have largely been established by measuring the output of neurons, i.e. their spiking activity. How excitation and inhibition are reflected in the local field potential (LFP) is little understood. As this can bear on the interpretation of human fMRI BOLD data and on our understanding of the mechanisms of local field potential oscillations, we measured spatial integration and centre–surround properties in single- and multiunit recordings of V1 in the awake fixating macaque monkey, and compared these to spectral power in different frequency bands of simultaneously recorded LFPs. We quantified centre–surround organization by determining the size of the summation and suppression area in spiking activity as well as in different frequency bands of the LFP, with the main focus on the gamma band. Gratings extending beyond the summation area usually inhibited spiking activity while the LFP gamma-band activity increased monotonically for all grating sizes. This increase was maximal for stimuli infringing upon the near classical receptive field surround, where suppression started to dominate spiking activity. Thus, suppressive influences in primary cortex can be inferred from spiking activity, but they also seem to affect specific features of gamma-band LFP activity.     

Monoclonal antibody to neurofilament protein (SMI-32) labels a subpopulation of pyramidal neurons in the human and monkey neocortex

A monoclonal antibody that recognizes a nonphosphorylated epitope on the 168 kDa and 200 kDa subunits of neurofilament proteins has been used in an immunohistochemical study of cynomolgus monkey (Macaca fascicularis) and human neocortex. This antibody, SMI-32, primarily labels the cell body and dendrites of a subset of pyramidal neurons in both species. A greater proportion of neocortical pyramidal neurons were SMI-32 immunoreactive (ir) in the human than in the monkey. SMI-32-ir neurons exhibited consistent differences in the intensity of their immunoreactivity that correlated with cell size. The cellular specificity of SMI-32 immunoreactivity suggests that a subpopulation of neurons can be distinguished on the basis of differences in the molecular characteristics of basic cytoskeletal elements such as neurofilament proteins. The size, density, and laminar distribution of SMI-32-ir neurons differed substantially across neocortical areas within each species and between species. Differences across cortical areas were particularly striking in the monkey. For example, the anterior parainsular cortex had a substantial population of large SMI-32-ir neurons in layer V and a near absence of any immunoreactive neurons in the supragranular layers. This contrasted with the cortical area located more laterally on the superior temporal gyrus, where layers III and V contained substantial populations of large SMI-32-ir neurons. Both areas differed significantly from the posterior inferior temporal gyrus, which was distinguished by a bimodal distribution of large SMI-32-ir neurons in layer III. Differences across human areas were less obvious because of the increase in the number of SMI-32-ir neurons. Perhaps the most notable differences across human areas resulted from shifts in the density of the larger SMI-32-ir neurons in deep layer III. A comparison between the species revealed that isocortical areas exhibited greater differences in their representation of SMI-32-ir neurons than primary sensory or transitional cortical areas. A comparison of distribution patterns of SMI-32-ir neurons across monkey cortical areas and data available on the laminar organization of cortical efferent neurons suggests that a common anatomic characteristic of this chemically identified subpopulation of neurons is that they have a distant axonal projection. Such correlations of cell biological characteristics with specific elements of cortical circuitry will further our understanding of the molecular and cellular properties that are critically linked to a given neuron's role in cortical structure and function.     

Sets of neurons in somatic cerebral cortex of the cat and their ontogeny

The process of set formation is briefly reviewed and five monothetic schemes for classification of neurons in the somatic cerebral cortex are described. Criteria for evaluation of neuronal sets are presented and applied to the five different monothetic classification schemes. Classification by size and distribution of peripheral receptive fields orders existing data on cortical neurons better than classification by possession of an axon in the pyramidal tract, by modality, by lability of receptive field, or by ‘lemniscal properties’; however, no monothetic scheme orders all the data. A useful polythetic scheme, using s and m terminology is suggested. The ontogeny of the cerebral cortex is reviewed in detail. It is suggested that sa. neurons are Golgi type II neurons while m neurons are Golgi type I neurons. The hypothesis is presented that wide-field or m neurons develop and are recognizable before small-field or sa. neurons in ontogeny. Evidence regarding this hypothesis is indirect, often conflicting, but suggestive that the hypothesis may be correct. The idea that m neurons may also be phylogenetically older than sa neurons is presented and shown to be consistent with ontogenetic data and interpretations.     

Postnatal maturation of nonpyramidal neurons in the visual cortex of the cat

A Golgi study of nonpyramidal neurons in the visual cortex of kittens aged from 1 to 80 days revealed that different neuronal types undergo a differential sequence of maturation. The earliest nonpyramidal cells to differentiate are large multipolar cells of layers 3-5, which appear around birth and whose axons gradually establish long lateral, intracortical connections. They are followed by spiny stellate cells of layer 4, which appear in the first postnatal, week, and by neuroglioform cells in layers 4 and 5, a cell type which at 10 days displays a highly differentiated axonal plexus. In general, most classes of local axon cells can be identified by the end of the second week, though still possessing a very immature morphology, the axonal-tuft cells of layer 2 maturing later, in the third week. With some exceptions, most neurons exhibit an adultlike axonal arborization by the end of the first month; however, immature chandelier terminals are observed until the 40th day, and in kittens aged from 30 to 80 days, the vertical terminal segments of chandelier cells are larger than in the adult. Some neuronal types seem to present an exuberant growth of axonal fibers in the late postnatal period and a subsequent reduction up to the adult stage.     

Differential effects of neurotrophins on ocular dominance plasticity in developing and adult cat visual cortex

In the present study we examine the influence of neurotrophins on experience-dependent synaptic rearrangement in developing and adult visual cortex. Brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF) was continuously infused into cortical area 18, and the functional architecture of the cortex was examined by use of optical and electrophysiological recording techniques. In kittens, BDNF infusion during monocular deprivation (MD) reversed the normally occurring ocular dominance (OD) shift towards the non-deprived eye so that the deprived eye dominated the BDNF-treated cortex after MD. Under conditions of equal activation of thalamocortical synapses, i.e. when animals were either subject to binocular deprivation (BD) or reared without deprivation, BDNF infusion did not disrupt binocularity of cortical units, but reversed the natural OD bias towards the contralateral eye in favour of the ipsilateral eye. In addition, BDNF treatment in kittens led to a loss of the orientation selectivity of cortical units irrespective of rearing conditions. In adult animals, BDNF influenced neither OD distributions nor orientation selectivity. The effect of NGF was markedly different. It was ineffective in kittens but in adult animals it caused a shift of OD towards the deprived eye when MD was combined with NGF infusion. However, in this case orientation selectivity was preserved. Thus, both neurotrophins have profound activity- and age-dependent effects on the functional architecture of the visual cortex. Moreover, our results indicate that simple substitution of neurotrophins in excess is unlikely to compensate for deprivation effects by preserving or restoring the normal functional architecture of the cortex.     

Impairment of binocular vision in the adult cat induces plastic changes in the callosal cortical map

In the primary visual cortex of normally reared adult cat, neurons activated through the corpus callosum are almost entirely located at the 17/18 border. They display small receptive fields distributed along the central vertical meridian of the visual field and are orientation selective. Here we demonstrate that a few weeks of monocular deprivation or unilateral convergent strabismus produced in adulthood does not modify the cortical distribution of these neurons, but leads to an increase of their receptive field size mainly toward the ipsilateral hemifield and to a loss of their orientation selectivity. We conclude that manipulation of binocular vision in the adult modifies neither the location of the primary callosal cortical map nor its retinotopy. In contrast, it induces functional plastic changes in this map which lead to a significant widening of the area of visual space signalled through the corpus callosum. These plastic changes are interpreted as the result of the strengthening of normally hidden subthreshold synaptic inputs.     

Sublaminar organization within layer VI of the striate cortex in Galago.

In this study we examined the organization of projections from the striate cortex to the dorsal lateral geniculate (GL) and pulvinar (PUL) nuclei in the prosimian Galago by using retrograde transport methods. Injections of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the PUL labeled two bands of cells in the striate cortex: the first consisted of large pyramidal cells in the upper half of layer V; the second consisted of small and medium-size pyramidal cells located in the deepest part of layer VI. The location of cells within layer VI coincided with a clear cytoarchitectonic sublayer, VIb, which contains fewer and paler staining cells than VIa. Injections of WGA-HRP involving all layers of the GL produced an uninterrupted band of pyramidal cells distributed throughout layer VI (a and b), including the region labeled after injections into the PUL. Thus as a first approximation, layer VI can be divided into an upper tier (VIa) that projects only to the GL and a lower tier (VIb) that projects to both the GL and PUL. Injections of WGA-HRP that were restricted to one or a few GL layers revealed a further refinement of the subdivisions within layer VI. Injections into the parvicellular and intercalated (or koniocellular) layers of the GL labeled neurons predominantly in the upper half of layer VIa, whereas injections restricted to the magnocellular layers labeled neurons in the lower half of layer VIa and in layer VIb. In order to determine whether individual neurons in layer VIb send axon collaterals to both the GL and PUL, we injected WGA-HRP into one nucleus and fluorescent rhodamine latex beads into the other. In three experiments, we found only one double-labeled cell. In sum, the results provide evidence that layer VI is divided into at least three sublayers: upper VIa, which projects to the intercalated and parvicellular GL layers; lower VIa, which projects to the magnocellular GL layers; and VIb, which sends separate projections to the magnocellular layers of the GL and to the PUL. The segregation observed is sufficiently discrete to propose the existence of multiple, descending pathways from layer VI of the striate cortex that complement those ascending from the GL and PUL.     

Direction selectivity of neurons in the visual cortex is non‐linear and lamina‐dependent

Neurons in the visual cortex are generally selective to direction of movement of a stimulus. Although models of this direction selectivity (DS) assume linearity, experimental data show stronger degrees of DS than those predicted by linear models. Our current study was intended to determine the degree of non‐linearity of the DS mechanism for cells within different laminae of the cat's primary visual cortex. To do this, we analysed cells in our database by using neurophysiological and histological approaches to quantify non‐linear components of DS in four principal cortical laminae (layers 2/3, 4, 5, and 6). We used a DS index (DSI) to quantify degrees of DS in our sample. Our results showed laminar differences. In layer 4, the main thalamic input region, most neurons were of the simple type and showed high DSI values. For complex cells in layer 4, there was a broad distribution of DSI values. Similar features were observed in layer 2/3, but complex cells were dominant. In deeper layers (5 and 6), DSI value distributions were characterized by clear peaks at high values. Independently of specific lamina, high DSI values were accompanied by narrow orientation tuning widths. Differences in orientation tuning for non‐preferred vs. preferred directions were smallest in layer 4 and largest in layer 6. These results are consistent with a non‐linear process of intra‐cortical inhibition that enhances DS by selective suppression of neuronal firing for non‐preferred directions of stimulus motion in a lamina‐dependent manner. Other potential mechanisms are also considered.     

Layer VI in cat primary auditory cortex: Golgi study and sublaminar origins of projection neurons

The organization of layer VI in cat primary auditory cortex (AI) was studied in mature specimens. Golgi-impregnated neurons were classified on the basis of their dendritic and somatic form. Ipsilateral and contralateral projection neurons and the corticogeniculate cells of origin were labeled with retrograde tracers and their profiles were compared with the results from Golgi studies. Layer VI was divided into a superficial half (layer VIa) with many pyramidal neurons and a deeper part (layer VIb) that is dominated by horizontal cells. Nine types of neuron were identified; four classes had subvarieties. Classical pyramidal cells and star, fusiform, tangential, and inverted pyramidal cells occur. Nonpyramidal neurons were Martinotti, multipolar stellate, bipolar, and horizontal cells. This variety of neurons distinguished layer VI from other AI layers. Pyramidal neuron dendrites contributed to the vertical, modular organization in AI, although their apical processes did not project beyond layer IV. Their axons had vertical, intrinsic processes as well as corticofugal branches. Horizontal cell dendrites extended laterally up to 700 μm and could integrate thalamic input across wide expanses of the tonotopic domain. Connectional experiments confirmed the sublaminar arrangement seen in Nissl material. Commissural cells were concentrated in layer VIa, whereas corticocortical neurons were more numerous in layer VIb. Corticothalamic cells were distributed more equally. The cytological complexity and diverse connections of layer VI may relate to a possible role in cortical development. Layer VI contained most of the neuronal types found in other layers in AI, and these cells form many of the same intrinsic and corticofugal connections that neurons in other layers will assume in adulthood. Layer VI, thus, may play a fundamental ontogenetic role in the construction and early function of the cortex. J. Comp. Neurol. 404:332–358, 1999. © 1999 Wiley-Liss, Inc.