Maturation of pyramidal cell form in relation to developing afferent and efferent connections of rat somatic sensory cortex.

Golgi and axonal labeling methods were used to examine the maturation of pyramidal cells in layers III and V of the rat somatic sensory cortex. The material came from animals late in the gestation period, postnatal, ranging from 0 to 43 days of age and at maturity. Special attention was paid to the period (0–7 days of age) during which it is known that thalamic and callosal fibers grow into the cortex. It is shown that the basic features of the pyramidal cell form are established before the long afferent fibers arrive in layers III and V and before the large number of synapses are established in these layers. Nevertheless, considerable dendritic growth and spine formation occurs after the afferent fibers establish an adult-like pattern of distribution. It is also shown that even at 1 day of age, the axons of pyramidal cells in all layers have reached the vicinity of targets such as the striatum, thalamus, brainstem, spinal cord and contralateral cortex.At 0–1 day the immature pyramidal cells are essentially bipolar in the upper cortical plate, but in the developing infragranular layers they have a few short, almost spine-free, basal dendrites and, rarely, a few oblique branches of the apical dendrite. The apical dendrite extends to the pial surface and the dendritic branches end in growth cones. The dendrites of cells in all layers increase in size and complexity of branching over the first postnatal week; the maturation of dendrites in layer V leads that of dendrites in the supragranular layers by about 2–3 days. As maturation proceeds, basal dendrites acquire secondary and tertiary branches and more oblique branches appear on the apical dendrite. Dendritic spines appear after 4 days of age but remain sparse up to 7–8 days. At 14 days of age, the spine density is much higher than in 7-day-old animals but remains at a much lower density than in 4-week-old, 6-week-old, or adult animals. By 7–14 days, the difference in maturity between superficial (layer III) and deep (layer V) pyramidal cells is difficult to discern qualitatively. All the pyramidal cells now have relatively complex, highly branched dendritic trees when compared to younger cells, but the dendritic tree is still immature in terms of the number, length and complexity of branching of the apical and basal dendritic systems.It can be concluded that the growth of the long axon of cortical pyramidal neurons precedes the acquisition of afferent connections and when these afferent fibers arrive in the cortex the dendritic tree of the pyramidal cell is still highly immature. Thus it remains possible that the finer modeling of the dendritic tree and the formation of spines may be affected by extrinsic influences such as the afferent fibers.     

Long term effects of callosal lesions in the auditory cortex of rats of different ages

The corpus callosum was sectioned in groups of rats 3, 12, and 24 months of age, and the auditory cortex was examined three months later to determine whether there were age-related differences in the morphological response to the partial deafferentation. Material from the three groups of long-term callosally-lesioned rats were compared with three groups of age-matched control animals. Analysis focused on those cortical layers known to receive the heaviest callosal projection (layers II and III) and those neurons known to be postsynaptic to callosal afferents (layer V pyramidal neurons). There were no age-related changes in cortical thickness or in the relative thickness of the cortical layers in the control groups. However, the apical dendrites of layer V pyramidal neurons did lose dendritic spines and became thinner with age. In all three lesion groups, the cortex became thinner without altering the relative thickness of cortical layers; there was a decrease in the relative density of apical dendrite spines in layer III, but an increase in the density of these spines in layer IV. Both effects varied with age. Spine decreases in layer III were greatest in older animals and spine increases in layer IV were greatest in younger animals. The mean diameters of apical dendrites decreased in the youngest group of lesioned animals but increased in the oldest group. The results indicate that the effects of callosal deafferentation are age dependent.     

Parvalbumin-immunoreactive neurons in the entorhinal cortex of the rat: localization, morphology, connectivity and ultrastructure

Summary We studied the distribution, morphology, ultrastructure and connectivity of parvalbumin-immunoreactive neurons in the entorhinal cortex of the rat. Immunoreactive cell bodies were found in all layers of the entorhinal cortex except layer I. The highest numbers were observed in layers II and III of the dorsal division of the lateral entorhinal area whereas the lowest numbers occurred in the ventral division of the lateral entorhinal area, Most such neurons displayed multipolar configurations with smooth dendrites. We distinguished a type with long dendrites and a type with short dendrites. We also observed pyramidal immunoreactive neurons. A dense plexus of immunoreactive dendrites and axons was prominent in layers II and III of the dorsal division of the lateral entorhinal area and the medial entorhinal area. None of the parvalbuminimmunoreactive cells became retrogradely labelled after injection of horseradish peroxidase into the hippocampal formation. By electron microscopy, immunoreactivity was observed in cell bodies, dendrites, myelinated and unmyelinated axons and axon terminals. Immunoreactive dendrites and axons occurred in all cortical layers. We noted many myelinated immunoreactive axons. Immunoreactive axon terminals were medium sized, contained pleomorphic synaptic vesicles, and established symmetrical synapses. Both horseradish peroxidase labelled and unlabelled immunonegative cell bodies often received synapses from immunopositive axon terminals arranged in baskets. Synapses between immunoreactive axon terminals and unlabelled dendritic shafts and spines were abundant. Synapses with initial axon segments occurred less frequently. In addition, synaptic contacts were present between immunopositive axon terminals and cell bodies and dendrites. Thus, the several types of parvalbumin-containing neuron in the entorhinal cortex are interneurons, connected to one another and to immunonegative neurons through a network of synaptic contacts. Immunonegative cells projecting to the hippocampal formation receive axo-somatic basket synapses from immunopositive terminals. This connectivity may form the morphological substrate underlying the reported strong inhibition of cells in layers II and III of the entorhinal cortex projecting to the hippocampal formation.     

Maturation of rat visual cortex. I. A quantitative study of Golgi-impregnated pyramidal neurons

Summary The early postnatal maturation of pyramidal neurons in layers II/III and V of the rat visual cortex has been examined in an attempt to elucidate some determinants of their mature morphology. Three indices have been quantified using Golgi-impregnated pyramidal cells: densities of spines along apical dendrites, numbers of primary basal dendrites and volumes of cell bodies. The mean density of spines on the apical dendrites of all pyramidal neurons increases in a stepwise fashion. The first significant increase occurs between days 6 and 9 and the second, between days 12 and 15; these increases may correlate with the arrival of geniculate afferents and with the opening of the eyes, respectively. In younger animals, the distribution of spines along the apical shafts is relatively even, whereas in older animals, spine density increases significantly over the proximal 125 m portion and is relatively constant over the remaining distal portion. By day 21, layer V pyramidal cells have acquired more primary basal dendrites and larger somatic volumes than layer II/III cells. Furthermore, as the cells mature the rates of change in these characteristics are significantly different for neurons in layer II/III and in layer V. For both cell populations, the mean number of primary basal dendrites increases to a maximum before falling to a steady level, but for neurons in layer V, the maximum is higher and attained three days earlier than for layer II/III cells. Moreover, the increase in volume of cell bodies of layer V neurons begins three days before that of layer II/III cells. This three day phase difference in maturation may reflect the cell birth dates, since autoradiographic evidence indicates that layer V pyramidal neurons reach the cortical plate about three days prior to those which occupy layer II/III in the adult visual cortex.     

Density and morphology of dendritic spines in mouse neocortex

Dendritic spines of pyramidal cells are the main postsynaptic targets of cortical excitatory synapses and as such, they are fundamental both in neuronal plasticity and for the integration of excitatory inputs to pyramidal neurons. There is significant variation in the number and density of dendritic spines among pyramidal cells located in different cortical areas and species, especially in primates. This variation is believed to contribute to functional differences reported among cortical areas. In this study, we analyzed the density of dendritic spines in the motor, somatosensory and visuo-temporal regions of the mouse cerebral cortex. Over 17,000 individual spines on the basal dendrites of layer III pyramidal neurons were drawn and their morphologies compared among these cortical regions. In contrast to previous observations in primates, there was no significant difference in the density of spines along the dendrites of neurons in the mouse. However, systematic differences in spine dimensions (spine head size and spine neck length) were detected, whereby the largest spines were found in the motor region, followed by those in the somatosensory region and those in visuo-temporal region.     

The cytoarchitecture and soma-dendritic arbors of the pyramidal neurons of aged rat sensorimotor cortex: An intracellular dye injection study

We studied the cytoarchitecture and dendritic arbors of the output neurons of the sensorimotor cortex of aged rats and found that although individual cortical layer became thinner, the overall cytoarchitecture and neuron densities remained comparable to those of young adults. To find out whether aging affects cortical outputs we studied the soma-dendritic arbors of layers III and V pyramidal neurons, main output neurons of the cerebral cortex, using brain slice intracellular dye injection technique. With a fluorescence microscope, selected neurons were filled with fluorescence dye under visual guidance. Injected slices were resectioned into thinner sections for converting the injected dye into non-fading material immunohistochemically. The long apical dendritic trunk and branches could be routinely revealed. This allowed us to reconstruct and study the dendritic arbors of these neurons in isolation in 300-μm-thick dimension. Analysis shows that their cell bodies did not shrink, but the densities of spines on dendrites and the total dendritic length significantly reduced. Among spines, those with long thin stalks thought to be involved in memory acquisition appeared to be reduced. These could underlie the compromise of sensorimotor functions following aging.     

The termination of callosal fibres in the auditory cortex of the rat. A combined Golgi--electron microscope and degeneration study

When the corpus callosum of the rat is sectioned, the callosal fibres in the cerebral cortex undergo degeneration. In the auditory cortex (area 41) the degenerating axon terminals form asymmetric synapses, and the vast majority of them synapse with dendritic spines. Some other synapse with the shafts of both spiny and smooth dendrites, and a few with the perikarya of non-pyramidal cells. The degenerating axon terminals are contained principally within layer II/III, in which they aggregate in patches. Using a technique in which neurons within the cortex are Golgi-impregnated, then gold-toned and examined in the electron microscope, it has been shown that the dendritic spines of pyramidal neurons with cell bodies in different layers receive the degenerating callosal afferents. The spines arise from the main apical dendritic shafts and their branches, from the dendrites of the apical tufts, and in some cases from the basal dendrites of the pyramidal neurons. The shafts of some pyramidal cell apical dendrites also form asymmetric synapses with callosal afferents. Since we have encountered no spiny non-pyramidal neurons in Golgi preparations of rat auditory cortex, and because other types of non-pyramidal cells have few dendritic spines, it is concluded that practically all of the dendritic spines synapsing with callosal afferents originate from pyramidal neurons.     

Dendritic spines in the visual cortex of the mouse: Introduction to a mathematical model

Summary The spines of apical dendrites of the layer V pyramidal cells of the area striata in the mouse represent a sequence of post-synaptic structures receiving a variety of contacts from terminal fibers derived fundamentally from short axon cells and superficial pyramidal cells. The study of Golgi preparations of mice 180 days old shows the existence of the most complicated terminal structures over portions of apical dendrites at the levels of layers III and IV. Observations on young mice reveals the terminations of the specific afferent fibers on the dendrites of short axon cells. A mathematical model which defines the distribution of spines along the apical dendrites is introduced. The principal equation of the model has been adjusted from the data processing of microscope countings through a series of programs written for an IBM 7070. The equation defines satisfactorily the different distributions of dendritic spines in mice 10–180 days old raised in normal conditions and in complete darkness. The equation defines also the distribution of dendritic spines in the visual cortex of mice enucleated at birth on one side, and the distribution along the apical dendrites of various cortical areas of the hamster, cat and man. The number of dendritic spines increases with the age of the subject and their distribution varies significantly according to the values of the parameters of the model.     

The immediate large-scale dendritic plasticity of cortical pyramidal neurons subjected to acute epidural compression

Head trauma and acute disorders often instantly compress the cerebral cortex and lead to functional abnormalities. Here we used rat epidural bead implantation model and investigated the immediate changes following acute compression. The dendritic arbors of affected cortical pyramidal neurons were filled with intracellular dye and reconstructed 3-dimensionally for analysis. Compression was found to shorten the apical, but not basal, dendrites of underlying layer III and V cortical pyramidal neurons and reduced dendritic spines on the entire dendritic arbor immediately. Dendrogram analysis showed that in addition to distal, proximal apical dendrites also quickly reconfigured. We then focused on apical dendritic trunks and explored how proximal dendrites were rapidly altered. Compression instantly twisted the microtubules and deformed the membrane contour of dendritic trunks likely a result of the elastic nature of dendrites as immediate decompression restored it and stabilization of microtubules failed to block it. Subsequent adaptive remodeling restored plasmalemma and microtubules to normal appearance in 3 days likely via active mechanisms as taxol blocked the restoration of microtubules and in addition partly affected plasmalemmal reorganization which presumably engaged recycling of excess membrane. In short, the structural dynamics and the associated mechanisms that we revealed demonstrate how compression quickly altered the morphology of cortical output neurons and hence cortical functions consequently.     

Morphology of spiny neurons in the human entorhinal cortex: intracellular filling with lucifer yellow

The present study was designed to investigate the morphology of spiny neurons in the human entorhinal cortex. Coronal entorhinal slices (n = 67; 200 microm thick) were obtained from autopsies of three subjects. Spiny neurons (n = 132) filled with Lucifer Yellow were analysed in different subfields and layers of the entorhinal cortex. Based on the shape of the somata and primary dendritic trees, spiny neurons were divided into four morphological categories; (i) classical pyramidal, (ii) stellate, (iii) modified stellate, and (iv) horizontal tripolar cells. The morphology of filled neurons varied more in different layers than in the different subfields of the entorhinal cortex. In layer II, the majority (81%) of spiny neurons had stellate or modified stellate morphology, but in the rostromedial subfields (olfactory subfield and rostral subfield) there were also horizontal tripolar neurons. Dendritic branches of layer II neurons extended to layer I (94%) and to layer III (83%). Unlike in layer II, most (74%) of the filled neurons in layers III, V and VI were classical pyramidal cells. The majority of pyramidal cells in the superficial portion of layer III had dendrites that extended up to layer II, occupying the space between the neuronal clusters. Some dendrites reached down to the deep portion of layer III. Apical dendrites of layer V and VI pyramidal cells traveled up to the deep portion of layer III.Our data indicate that the morphology of spiny neurons in different layers of the human entorhinal cortex is variable. Vertical extension of dendritic branches to adjacent layers supports the idea that inputs terminating in a specific lamina influence target cells located in various entorhinal layers. There appears to be more overlap in the dendritic fields between superficial layers II and III than between the superficial (II/III) and deep (V/VI) layers, thus supporting the idea of segregation of information flow targeted to the superficial or deep layers in the human entorhinal cortex.     

Self-stimulation rewarding experience induced alterations in dendritic spine density in CA3 hippocampal and layer V motor cortical pyramidal neurons.

Self-stimulation rewarding experience induced alterations in the numerical density of spines in CA3 hippocampal and layer V motor cortical pyramidal neurons in adult male Wistar rats was evaluated. Self-stimulation experience was provided 1 h daily over a period of 10 days through stereotaxically implanted bipolar stainless steel electrodes bilaterally in lateral hypothalamus and substantia nigra-ventral tegmental area. After 10 days, rats were killed and the hippocampus and motor cortex were processed for rapid Golgi staining procedure. The dendritic spine densities were studied in CA3 hippocampal and layer V motor cortical pyramidal neurons. The spine densities were quantified in five successive segments of 15.2 microm up to a distance of 76 microm. Apical dendrites were classified as mainshaft, sub branch, oblique shaft-I, oblique shaft-II, primary branch; and basal dendrites as main shaft, primary branch and secondary branch. A grand total of 864 CA3 hippocampal and 1008 layer V motor cortical dendrites were analysed for spine counting in different groups of rats. The results revealed a significant (P<0.001; ANOVA, F-test) increase in the number of spines in all the categories of dendrites in apical and basal regions in both hippocampal and motor cortical neurons in self-stimulation group of rats. Such changes were not observed either in sham control, experimenter-administered or normal control groups of rats. The self-stimulation induced increase in the spine density suggests an increase in the postsynaptic receptive field in CA3 hippocampal and layer V motor cortical neurons. This might enhance the efficacy of synaptic transmission in these neurons. Our study clearly demonstrated the self-stimulation rewarding experience induced postsynaptic plasticity in hippocampal and motor cortical pyramidal neurons.     

Somatostatin immunoreactive neurons in rat visual cortex: A light and electron microscopic study

Summary Somatostatin immunoreactive neurons in rat visual cortex were examined in the light and electron microscopes using an antibody to the tetradecapeptide form of somatostatin. Somatostatin immunoreactive neurons were found to belong only to non-pyramidal classes. They are of five main types: multipolar neurons with either thin or thick dendrites; small and large bipolar neurons; bitufted neurons; horizontal neurons; and neurons in the subcortical white matter. Of the immunoreactive neurons, multipolar neurons are the most common and account for 30% of the population, while bipolar and bitufted neurons make up 25% and 15% of the immunoreactive population, respectively; the least common somatostatin immunoreactive neurons are the horizontal and subcortical white matter neurons. Occasional multipolar neurons with thick dendrites have a prominent ascending dendrite so that they resemble pyramidal cells in the light microscope, but electron microscopic examination confirms that, like all other somatostatin-positive cells, they are non-pyramidal neurons, for they have both symmetric and asymmetric synapses on their cell bodies.Somatostatin-positive neurons are distributed among all the cortical layers and the subcortical white matter but they are more common in two laminae, one coinciding with layer II/III and the other with layers V and VI. The multipolar and bipolar neurons are distributed in similar proportions in these upper and lower cortical laminae, while bitufted neurons are more common in upper laminae and horizontal neurons are predominantly located in layer VI.     

The projection of the visual cortex on the Clare-Bishop area in the cat

Summary Following large lesions of the cat visual cortex, the distribution of degenerating terminal boutons in the Clare-Bishop area was studied electron microscopically. Degenerating boutons were found throughout the cortical layers but mostly in layer III (51% of the total number of degenerating boutons) and layer V (24%). A smaller number of boutons were found in layers II (12%) and IV (9%), and very few in layers VI (3%) and I (1%). No degenerating terminals were observed in the upper two-thirds of layer I. Seventy-six per cent of the total degenerating boutons terminated on dendritic spines, 22% on dendritic shafts, and 2% on somata. Some degenerating boutons made synaptic contacts with somata and dendrites of nonpyramidal neurons. For example, one degenerating bouton was observed in contact with an apical dendrite of a fusiform cell. Three examples of dendritic spines, with which degenerating boutons made synaptic contacts, were found to belong to spinous stellate cells. No degenerating boutons were observed making synaptic contacts with profiles that could conclusively be traced to pyramidal cell somata.     

Neuronal alterations in patients with dementia: a Golgi study on biopsy samples

Golgi-impregnated neurons in biopsy samples of the cerebral cortex (area 8) of patients with Alzheimer's disease (AD), Pick's disease (PD) and Creutzfeldt-Jakob disease (CJD), but not in control samples, have swellings in the proximal and mid regions of dendrites of pyramidal and non-pyramidal cells that differ from normal dendritic varicosities. Dendritic outgrowths, isolated or in clusters, and covered with spines occur only in neurons with reduced dendritic arbors mainly located in the vicinity of senile plaques. Degenerating pyramidal and non-pyramidal neurons, although distributed throughout the cerebral cortex in CJD and PD, predominate in layers II, III and VIb in patients with AD.     

The thalamic projection to cat visual cortex: ultrastructure of neurons identified by Golgi impregnation or retrograde horseradish peroxidase transport

Specific afferents to the primary visual cortex of the cat were identified by electron microscopy after electrolytic lesions of the lateral geniculate nucleus. Postsynaptic target neurons were marked by either Golgi impregnation or horseradish peroxidase retrogradely transported from the opposite visual cortex. The type and the location of identified neurons were determined by light microscopy before further investigation by electron microscopy. Different pyramidal neurons have relatively homogeneous ultrastructural characteristics, but non-pyramidal neurons, divisible into large and small, spiny, sparsely-spiny and non-spiny, vary in their synaptology. Thalamo-cortical afferents have been found to all neuronal types examined in layer IV and lower layer III, including horseradish peroxidase-filled callosal cells. These include pyramidal cells of layer III which receive thalamo-cortical afferents mainly on spines of apical and basal dendrites, but also on basal dendritic shafts. Layer V pyramids receive thalamo-cortical input to apical dendritic spines. All types of layer IV non-pyramidal neurons studied are contacted by geniculate terminals on dendritic spines and shafts and directly on the cell body.We conclude that input to the visual cortex is organized on both hierarchical and parallel bases.     

Expression of nerve growth factor and its receptors in the somatosensory-motor cortex of Macaca nemestrina

The present study was designed to examine the nerve growth factor (NGF) system (ligand and receptor-expressing neurons) in the somatosensory (areas 1, 3a, and 3b) and motor (area 4) cortices of the mature macaque. Light and electron microscope immunohistochemistry was used to assess the distribution and identity of NGF-, p75-, and trk-expressing elements. In each cortical area examined, NGF-positive neuronal somata were distributed through all laminae; most immunolabeled neurons were in layers II, III, and V. Based upon light microscope criteria (e.g., the morphology of proximal dendrites), both pyramidal and stellate neurons expressed NGF. Of the identifiable NGF- immunoreactive cells, 92% were pyramidal neurons and the remainder was stellate neurons. The electron microscope study showed that most (88%) NGF-positive somata formed symmetric synapses, whereas the others formed both symmetric and asymmetric synapses. As the somata of pyramidal neurons form only symmetric synapses and those of inhibitory stellate neurons form both symmetric and asymmetric somatic synapses, the ultrastructural data support the light microscopic analyses. In contrast, neurotrophin receptors, p75 and trk, were expressed chiefly by the cell bodies of layer V pyramidal neurons and the supragranular neuropil. At the ultrastructural level, receptor-positive profiles were post-synaptic elements (e.g., dendritic shafts and spines) and the concentration of immunoreactivity was greatest in the vicinity of post-synaptic densities. Thus, NGF regulatory systems parallel excitatory and inhibitory neurotransmitter systems. Cortex contains the morphological framework by which pyramidal and/or inhibitory stellate neurons can affect the activity of post-synaptic pyramidal neurons via anterograde and autocrine/paracrine NGF systems.     

Bipolar neurons in rat visual cortex: A combined Golgi-electron microscope study

Summary Golgi-impregnated bipolar neurons in rat visual cortex have been examined by both light and electron microscopy. Bipolar neurons are encountered throughout layers II to V and are recognized by their spindle-shaped cell bodies and vertically elongate, narrow dendritic trees which may traverse the cortex from layer II to layer V. Although a single primary dendrite usually extends from each end of the cell body, two primary dendrites may extend from one pole, usually the lower one, and an additional short dendrite may emerge from one side. In the electron microscope gold-toned Golgi-impregnated neurons are seen to have folded nuclear envelopes and except at the poles of the cell body where the dendrites emerge, the nucleus is surrounded by only a thin rim of cytoplasm. Both the cell body and the dendrites form asymmetric and symmetric synapses. Usually the axon of a bipolar neuron arises from one of the primary dendrites and it soon assumes a vertical orientation, to either descend or ascend through the cortical neuropil. Some bipolar neurons have myelinated axons and only the initial portion is impregnated in Golgi preparations, but when they are unmyelinated the axons can be seen to form vertical plexuses and asymmetric synapses. Most commonly the terminals synapse with dendritic spines, some of which are derived from apical dendrites of pyramidal cells, but other terminals synapse with the shafts of apical dendrites, and with the cell bodies and dendrites of nonpyramidal cells.It is apparent that these bipolar neurons are the cells which others have shown to label specifically with antisera to vasoactive intestinal polypeptide (VIP), and it is suggested that the prime role of these cells in the cerebral cortex is to excite the clusters of pyramidal cells.     

The projection of the lateral geniculate nucleus to area 17 of the rat cerebral cortex. V. Degenerating axon terminals synapsing with Golgi impregnated neurons

Summary The sites of termination of afferents from the lateral geniculate nucleus to layer IV and lower layer III in area 17 of the rat visual cortex have been determined by use of a combined degeneration—Golgi/EM technique. Degeneration of geniculocortical axon terminals was produced by making lesions in the lateral geniculate body. After the animals had been allowed to survive for two days, the ipsilateral visual cortex was removed and impregnated by the Golgi technique. Suitably impregnated neurons and their processes in layer IV and lower layer III were then gold-toned and deimpregnated for examination in the electron microscope. A search was made for synapses between degenerating axon terminals and the gold-labelled postsynaptic neurons.Geniculocortical synapses were found to involve: (1) the spines of basal dendrites, as well as those of proximal shafts and collaterals of apical dendrites of layer III pyramidal neurons; (2) the spines of the apical dendritic shafts and collaterals of layer V pyramidal neurons; (3) the perikaryon and dendritic spines of a sparsely-spined stellate cell; and (4) the perikaryon and dendrites of a smooth, bitufted stellate cell. In view of this variety of postsynaptic elements it is suggested that all parts of the perikarya and dendrites of neurons contained in layer IV and lower layer III which are capable of forming asymmetric synapses can be postsynaptic to the thalamic input.Finally, an analysis of the known neuronal interrelations within the rat visual cortex is presented.     

Immunocytochemical localization of calcineurin in the adult and developing primary visual cortex of cats

An immunocytochemical method was used to localize calcineurin, a calcium-dependent calmodulinstimulated protein phosphatase, in the primary visual cortex of developing and adult cats. In the adult calcineurin immunoreactivity exhibits a laminar distribution with dense labeling in the upper half of layers II/III and two lightly labeled bands in lower layer IV and in layer VI. Most of the immunoreactive neurons are pyramidal in shape and appear to form a subpopulation of cortical neurons, but non-pyramidal neurons were also labeled, especially during early stages of postnatal development. The distribution pattern of calcineurin immunoreactivity showed developmental changes until at least 3 months of age. The number of calcineurin-positive cells abruptly increased at 3 weeks, and heavily labeled neurons appeared in a well-delineated band in layer IV between 3 and 5 weeks of age. At 6 to 10 weeks, neurons in layers II/III also became strongly immunoreactive. At this developmental stage intensely stained cells were thus distributed throughout layers II to IV. Thereafter, there was a marked decrease in the number of immunoreactive cells in layer IV and beyond 12 weeks the distribution pattern of calcineurin immunoreactivity became similar to that of adult animals. These changes of calcineurin expression show some relation with the inside-out pattern of cortical maturation and with the time course and the laminar selectivity of use-dependent malleability. Therefore, we suggest that calcineurin may be involved in processes of neuronal differentiation and experience-dependent plasticity.