Apical dendritic spines of the visual cortex and light deprivation in the mouse

Summary The effects of light deprivation on the number of apical dendritic spines have been studied in the visual cortex of the mouse. In the portion of the apical dendrites of layer V-pyramidal cells traversing layer IV, dendritic segments of 50 in length from different cells were selected. The number of spines on each of 50 different segments per animal was counted. The countings were done in the areae striata and temporalis prima from mice raised in complete darkness since birth up to 22–25 days old. The observations were compared with the countings obtained in the areae striata and temporalis prima from mice raised under normal conditions. The results indicated that mice raised in darkness had a significant reduction in the number of spines per dendritic segment at the level of layer IV in area striata when compared with control animals. No significant difference was found in the number of spines per dendritic segment in layer IV between both groups of normal and dark raised mice in the area temporalis prima. The mean number of dendritic spines per consecutive segments along complete apical dendrites of layer V-pyramidal cells in area striata has been found to increase exponentially with the distance from the cell body. The same exponential relation, but with somewhat lower values, was obtained in the apical dendrites in area striata in mice raised in darkness. The significance of these findings were discussed. It was concluded that: First, visual sensory deprivation affect the fine structure of the central nervous system. Second, the results observed support the assumption that structural changes in the nerve cells occur as the result of experience.     

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.     

Postnatal development of the visual cortex of the mouse after enucleation at birth

Summary Quantitative data in the neocortex up to the age of 180 days (neuronal densities, number of neurones, glial cells, dendritic intersections and spines) were compared in normal mice and mice enucleated at birth.Bilateral enucleation induced an increase of neuronal density in all cortical layers of areas 17, 18a, and 41, the supragranular layers II–III being more affected than layers IV–VI. This was noticed in layer II 10 days after the operation and was maximal in all layers between 30 and 60 days; at 180 days there was some return to normal of the neuronal density in all layers. The total number of neurones and glial cells were the same in the bilaterally enucleated mice as in the controls. No reaction in dendritic branching was evident for pyramids of layers III and V in areas 17 and 41 after bilateral enucleation. In contrast the number of spines was reduced on the apical dendrites of pyramids from layers III and V in area 17, but not in area 41.After unilateral enucleation the reaction was less severe and delayed compared with bilateral enucleation, the first signs of increase of neuronal density appearing 30 days after the lesion in the contralateral hemisphere. The contralateral areas 17 and 18a were more affected than the ipsilateral ones and area 41 showed no change compared to the control. As after bilateral enucleation, layers IV and V were least affected by unilateral enucleation in both ipsi- and contralateral cortices.These results suggest that deafferentation in an immature system affects the development of all cortical layers but with a greatest intensity in supragranular layers, which are not the main direct targets of thalamo-cortical input.Supported by the Swiss National Research Foundation, Grants no. 3-641-71 and 3-434-74     

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.     

Loss of dendritic spines in aging cerebral cortex

Summary Previous work has shown that the dendritic spines of pyramidal neurons of the cerebral cortex are sensitive to a wide variety of environmental and surgical manipulations. The present study shows that the normal aging process also affects these spines. The spines were studied with the light microscope in Golgi preparations from rats ranging in age from 3 to 29.5 months. Visible spines were counted on either 25 or 50 segments of the basal dendrites, apical dendrites, oblique branches, and terminal tufts of layer V pyramidal cells in area 17. A progressive loss of spines occurred at each of these loci. The smallest observed spine loss (24%) occurred on the dendrites of the terminal tuft, and the largest (40%) on the oblique branches. Age-related spine loss appears to affect all animals, and for animals of any one age the overall loss is similar. However, the cell-to-cell variability within an individual animal is pronounced, some cells with high spine densities being present at every age examined. As a general rule, there is a positive relationship between visible spine density along the apical dendrite as it traverses layer IV and the thickness of the dendrite. With advancing age, the relatively thick dendrites decrease in number so that the thinner dendrites make up an increasingly larger proportion of the total apical dendrite population. Questions that remain for the future include the genesis of the spine loss, its relation to other aging changes, and its functional significance for the neuron.Supported by United States Public Health Service Program Project Grant HDO-5796-03 and Research Grant NB-07016     

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.     

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.     

Distribution of synapses on an intracellularly labeled small pyramidal neuron in the cat motor cortex

Summary The morphological characteristics and distribution of synapses on a small pyramidal neuron in layer III of the cat motor cortex have been studied by combining intracellular HRP staining and electron microscopic examination. The stained neuron showed spiny apical and basal dendritic profiles under the light microscope, and exhibited the morphological features of a pyramidal neuron. Ultrastructural analysis indicated that about 80% of the presynaptic terminals formed asymmetrical synapses with spines of distal apical and basal dendrites. On proximal apical dendrites, 64% of the synapses were found to make contact with spines, and 16.7% of the synapses were of symmetrical type and formed with dendritic shafts. Two types of terminal could be identified on the soma; they were alternately located and established symmetrical and asymmetrical synaptic contacts respectively. Possible functional implications are discussed.This paper is dedicated to Professor Fred Walberg on the occasion of his 70th birthday.     

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.     

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.     

The temporal evolution of the distribution of dendritic spines in the visual cortex of normal and dark raised mice

Summary A set of equations which define the distribution of spines along the apical dendrites have been developed. They are satisfied by the distribution of spines and its evolution with the age in the apicals of the layer V pyramidal cells of the visual cortex in normal and dark raised mice. The principal equation describes the distribution of the spines with three coefficients IF, B and K whose values have a functional relation with the age T of the animal. This relation has been defined by three additional equations whose coefficients were calculated. The equations have been used to predict the distribution of dendritic spines corresponding to age-groups of mice not previously studied and to find out the age of mice from the data of their known spine distribution resolving the inverse equations of IF (T) and B(T).     

Meynert cells in the primate visual cortex

The solitary cells of Meynert are distinguished by their specific location in layer V of the striate cortex, very large size, argyrophilia, and the profusion of neurofilaments in their dendrites and perikarya. They occur with greater frequency in the macular region of the cortex, spaced a minimal distance of 110 mum apart, at a maximum density of about 8000/cm-2. In the perifoveal cortex, Meynert cells are spaced about 400 mum apart and packed at a density of approximately 625/cm-2. Each Meynert cell has an apical dendrite and many large basal dendrites. The perikaryon and primary segments of all dendrites are spine-free; however, more distally a total of 36 000 spines are present, differentially disposed upon the dendritic surfaces. The basal dendrites bear over 77% of the spines on the Meynert cell, although they account for only 66% of the total length of the dendritic arborization. The first part of the apical dendrite is the most densely decorated with appendages, accounting for almost 10% of the spines on the whole dendritic tree. The apical dendrite becomes progressively less spiny as it passes through the superficial part of layers IV and III; less than 2.5% of the total number of spines of the Meynert cell project from this part of the apical dendrite. When the dendrite reaches layer II it bursts into an umbel of rapidly tapering branches. These are highly spinose, accounting for 8-13% of the cell's total, dispersed over only 23% of the linear dendritic length. It is suggested that this differential distribution of thorns can be correlated with the axonal inputs in the various cortical layers, and that the Meynert cell is designed to receive maximal information from layers I and II, and from layers V and VI, which are sources mainly of intracortical inputs. Thus the Meynert cell may be principally concerned with integrative information. In the perifoveal cortex, the basal dendrites of adjacent Meynert cells overlap considerably, and the apical terminal bouquet dendrites do not. In the macular cortex, because of the increased frequency of these neurons, both basaal and apical terminal dendritic fields overlap. A model is developed to illustrate these hypotheses.     

Quantification of synapses formed with apical dendrites of golgi-impregnated pyramidal cells: Variability in thalamocortical inputs,but consistency in the ratios of asymmetrical to symmetrical synapses

Five pyramidal cells from the posteromedial barrel subfield of mouse SmI cortex were labeled by Golgi impregnation and then gold-toned and de-impregnated (Fairén, Peters & Saldanha, 1977). Subsequently, 40 to 70 μm-long segments of their apical dendrites occurring in layer IV were graphically reconstructed from serial thin sections to determine the distribution of their synapses. Thalamocortical synapses onto these dendritic segments were identified by lesion-induced degeneration.The synaptic pattern of the pyramidal cell apical dendrites was consistent with previous reports in that most synapses occurred on spines and were asymmetrical and the smaller number of shaft synapses were primarily symmetrical. Some axospinous synapses were formed by degenerating thalamocortical axon terminals. The proportion of thalamocortical synapses onto reconstructed dendritic segments was different for different neurons. For example, thalamocortical axon terminals formed 15% of the synapses involving the spines of the reconstructed segment from a medium superficial layer V pyramidal cell and 10% of the synapses onto portions of the segment from a large layer VI pyramidal cell. In contrast, reconstructed dendritic segments of three other layer VI pyramidal cells formed no more than one thalamocortical synapse.An analysis of the distribution of synapses onto reconstructed dendritic segments revealed that the segments of 3 medium and large pyramidal cells had a ratio of about 12.5 asymmetrical synapses per symmetrical synapse, whereas the segments of 2 small pyramidal cells had ratios of only 6.5 asymmetrical synapses per symmetrical synapse. That these ratios fall into 2 distinct groups suggests that the relative number of asymmetrical and symmetrical synapses is stereotyped within populations of neurons.     

Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination

Fragile-X syndrome is a common form of mental retardation resulting from the inability to produce the fragile-X mental retardation protein. Qualitative examination of human brain autopsy material has shown that fragile-X patients exhibit abnormal dendritic spine lengths and shapes on parieto-occipital neocortical pyramidal cells. Similar quantitative results have been obtained in fragile-X knockout mice, that have been engineered to lack the fragile-X mental retardation protein. Dendritic spines on layer V pyramidal cells of human temporal and visual cortices stained using the Golgi-Kopsch method were investigated. Quantitative analysis of dendritic spine length, morphology, and number was carried out on patients with fragile-X syndrome and normal age-matched controls. Fragile-X patients exhibited significantly more long dendritic spines and fewer short dendritic spines than did control subjects in both temporal and visual cortical areas. Similarly, fragile-X patients exhibited significantly more dendritic spines with an immature morphology and fewer with a more mature type morphology in both cortical areas. In addition, fragile-X patients had a higher density of dendritic spines than did controls on distal segments of apical and basilar dendrites in both cortical areas. Long dendritic spines with immature morphologies and elevated spine numbers are characteristic of early development or a lack of sensory experience. The fact that these characteristics are found in fragile-X patients throughout multiple cortical areas may suggest a global failure of normal dendritic spine maturation and or pruning during development that persists throughout adulthood.     

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.     

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.     

Distribution and subcellular localization of calmodulin in adult and developing brain tissue

The distribution and subcellular localization of calmodulin in adult and developing cerebellum was studied in rats by immunocytochemistry. Calmodulin immunoreactivity was found both in neurons and in glial cells. Within neurons the staining was particularly intense in the cell nucleus and in dendrites, the cytoplasm of the cell body was more lightly stained than the nucleus, and light immunoreactivity was observed in axons. Electron microscopic analysis confirmed the association of calmodulin with the nuclear chromatin, while the nucleolus remained unstained. The reaction product was also found overlying the membranes of several organelles, in postsynaptic densities and decorating both dendritic and axonal microtubules. In developing Purkinje cells, calmodulin immunoreactivity was found as early as 5 days after birth. During the initial phases of dendritic development (5-10 days post-natal), the reaction product was associated with the organelles of the apical cone, while little or no staining was observed in the elongating dendrites or in the cell nucleus. Later in development, calmodulin was found in primary and secondary dendrites, and by 20 days after birth immunoreactivity appeared in the cell nucleus, and in the postsynaptic densities of immature spines located in dendrites. The presence of calmodulin in the apical cone suggests the possibility that this protein may participate in the regulation of microtubule formation during the initial stages of dendritic development. Its presence in dendrites at later stages (during the period of synaptogenesis) may indicate that it also participates in the formation of synapses between the parallel fibres and dendritic spines.     

Postnatal development of immunohistochemically localized spectrin-like protein (calspectin or fodrin) in the rat visual cortex: Its excessive expression in developing cortical neurons

Summary Postnatal development of the expression and localization of a membrane-associated cytoskeletal protein, calspectin (fodrin or brain spectrin), in the visual cortex, was immunohistochemically studied in newborn to adult rats, by using an anti-calspectin antibody. At birth, calspectin-immunoreactivity was already present at the plasma membrane and in the cytoplasm of neurons which were mostly pyramidal cells located in the upper part of the cortical subplate. Immature neurons located in the cortical plate were not stained by the antibody, suggesting that calspectin is expressed only in neurons which have differentiated or are differentiating.At postnatal days 2 to 7, immunoreactive neurons were dramatically increased in layers V and VI and very intense labelling was seen in the apical dendrites of layer V pyramidal cells. Most of the stained processes of these and other neurons showed signs of rapid dendritic growth, i.e. non-terminal as well as terminal growth cones and filopodia. At days 10 to 17, dendrites of pyramidal cells in layers II and III became clearly detectable, although still slender. At days 24 to 34, the basal dendrites of pyramidal cells in layers II, III and V became intensely immunoreactive and dendritic spines were visualized by the antibody. In the adult, however, the calspectin immunoreactivity became very weak and spines were not recognizable. At all the ages, axons and neuroglia were unstained. Also, most of the neurons in layer IV of the cortex were not immunoreactive.These results suggest that caispectin is most abundantly expressed in growing parts of the dendrites and spines. A hypothesis that calspectin may play a role in synaptic plasticity in the developing visual cortex is discussed.     

Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile‐X syndrome: A quantitative examination

Fragile‐X syndrome is a common form of mental retardation resulting from the inability to produce the fragile‐X mental retardation protein. Qualitative examination of human brain autopsy material has shown that fragile‐X patients exhibit abnormal dendritic spine lengths and shapes on parieto‐occipital neocortical pyramidal cells. Similar quantitative results have been obtained in fragile‐X knockout mice, that have been engineered to lack the fragile‐X mental retardation protein. Dendritic spines on layer V pyramidal cells of human temporal and visual cortices stained using the Golgi‐Kopsch method were investigated. Quantitative analysis of dendritic spine length, morphology, and number was carried out on patients with fragile‐X syndrome and normal age‐matched controls. Fragile‐X patients exhibited significantly more long dendritic spines and fewer short dendritic spines than did control subjects in both temporal and visual cortical areas. Similarly, fragile‐X patients exhibited significantly more dendritic spines with an immature morphology and fewer with a more mature type morphology in both cortical areas. In addition, fragile‐X patients had a higher density of dendritic spines than did controls on distal segments of apical and basilar dendrites in both cortical areas. Long dendritic spines with immature morphologies and elevated spine numbers are characteristic of early development or a lack of sensory experience. The fact that these characteristics are found in fragile‐X patients throughout multiple cortical areas may suggest a global failure of normal dendritic spine maturation and or pruning during development that persists throughout adulthood. © 2001 Wiley‐Liss, Inc.