Fractality of dendritic arborization of spinal cord neurons

Skeletonized images of Golgi impregnated neurons from the human, monkey, cat and rat dorsal horns were subjected to fractal analysis. These neurons have sparse branching of dendrite arbors. It is noticed that, in certain neuronal samples, some authors report that scaling range of experimentally declared fractals is extremely limited and spanned approximately between 0.5 and 2.0 decades. In order to retain our hypothesis that neurons with dendrites of uncomplicated shapes can be considered fractal over three decades of scale, we conducted four procedures: (i) we used the box-counting method, (ii) we scaled the box sizes as a power of 2, (iii) we chose the coefficient of correlation, measuring the "goodness of fit" of experimental data points to regression straight line, to be equal to or larger than 0.995, and (iv) we pointed out that all the neurons analyzed have a single fractal dimension measuring a global fractality showing no linear regions. As a control, we used some cerebellar Purkinje cells whose dendrite trees show much more complex structure and profuseness of branching. Since, generally, the neuronal structure is among the most complex of all cellular morphologies, we believe that supporting this hypothesis we advance the neuroscience and fractal theory.     

Specialization in pyramidal cell structure in the sensory-motor cortex of the Chacma baboon (Papio ursinus) with comparative notes on macaque and vervet monkeys

The systematic study of pyramidal cell structure has revealed new insights into specialization of the phenotype in the primate cerebral cortex. Regional specialization in the neuronal phenotype may influence patterns of connectivity and the computational abilities of the circuits they compose. The comparative study of pyramidal cells in homologous cortical areas is beginning to yield data on the evolution and development of such specialized circuitry in the primate cerebral cortex. Recently, we have focused our efforts on sensory-motor cortex. Based on our intracellular injection methodology, we have demonstrated a progressive increase in the size of, the branching structure in, and the spine density of the basal dendritic trees of pyramidal cells through somatosensory areas 3b, 1, 2, 5, and 7 in the macaque and vervet monkeys. In addition, we have shown that pyramidal cells in premotor area 6 are larger, more branched, and more spinous than those in the primary motor cortex (MI or area 4) in the macaque monkey, vervet monkey, and baboon. Here we expand the basis for comparison by studying the basal dendritic trees of layer III pyramidal cells in these same sensory-motor areas in the chacma baboon. The baboon was selected because it has a larger cerebral cortex than either the macaque or vervet monkeys; motor cortex has expanded disproportionately in these three species; and motor cortex in the baboon reportedly has differentiated to include a new cortical area not present in either the macaque or vervet monkeys. We found, as in monkeys, a progressive increase in the morphological complexity of pyramidal cells through areas 3b, 5, and 7, as well as from area 4 to area 6, suggesting that areal specialization in microcircuitry was likely to be present in a common ancestor of primates. In addition, we found subtle differences in the extent of the interareal differences in pyramidal cell structure between homologous cortical areas in the three species.     

Spinal branching of pyramidal tract neurons in the monkey

The branching pattern of individual pyramidal tract (PT) neurons of the monkey motor cortex was studied by activating these neurons antidromically from within the cervical motor nuclei and also from other regions of the spinal cord. 1. Fifty-four neurons were activated from motor nuclei in the cervical cord. Twenty-eight of these were activated from one segment and six (11%) were activated from motor nuclei of different segments. The remaining 20 neurons were activated from motor nuclei and also from unspecified region(s) of the gray matter. 2. Another 156 neurons were activated from unspecified regions(s) of cervical gray matter which could have been motor nuclei or outside the nuclei, and 64 of these were activated from more than one segment. 3. The branching patterns of PT neurons sending axons directly to motor nuclei innervating distal forelimb muscles suggested that they branch less than the rest of PT neurons.     

The axo-axonic interneuron in the cerebral cortex of the rat,cat and monkey

The synaptic connections of a specific type of identified cortical interneuron, the axo-axonic cell, were studied using Golgi methods. In the light-microscope axo-axonic cells were demonstrated in certain layers of the primary and secondary visual cortex of rat, cat and monkey, in the motor cortex of cat and in the subiculum and pyriform cortex of rat. The dendrites originating from the oval soma were oriented radially in a lower and upper spray within a cylinder about 100–150 μm wide. Electronmicroscopy of Golgi impregnated, gold-toned axo-axonic cells showed predominantly but not exclusively asymmetrical synaptic contacts on their dendrites and spines, few synaptic contacts on the perikarya some of which were asymmetrical, and no synaptic contacts on the axon initial segment. The axon usually arborized within the vicinity of the cell's own dendritic field in an area 100–200 μm in diameter. In the kitten motor cortex the axon of a neuron in layer III descended to layer VI, providing a columnar arborization.The axon formed specialized, 10–50 μm long terminal segments invariably oriented parallel with the axon initial segment of pyramidal cells. All 85 identified symmetrical-type synaptic contacts, deriving from 31 specialized terminal segments, were found exclusively on the axon initial segment of pyramidal neurons. Rare, lone boutons of axo-axonic cells also made synaptic contact only with axon initial segments, confirming the exclusive target specificity of these cells. In identified gold-toned boutons, flattened pleomorphic vesicles were present. Electron-microscopy showed that axons ending in specialized terminal segments may originate from myelinated fibres, indicating that Golgi impregnation has revealed only part of the axon. Counting of axon terminal segments, each of which was in contact with the axon initial segment of a pyramidal neuron, revealed 166 pyramidal neurons receiving input from a partially reconstructed axo-axonic cell in the motor cortex of the kitten, and 67 from another cell in the visual cortex of the cat. The convergence of five axo-axonic cells onto one pyramidal cell was demonstrated in the striate cortex of the cat by counting all synaptic contacts on three initial segments. Cells from a one-month-old kitten were compared with those of the adult. The axon of the developing neurons was more diverse, having many growth cones and filopodia which made no specialized membrane contacts. However, the developing specific terminal segments formed synapses only with axon initial segments.It is concluded that the presence of axo-axonic cells in all the species and cortical areas we have examined suggests their association with the structural design of pyramidal cells, wherever the latter occur, and with their participation in the information processing of pyramidal cells. Axo-axonic cells are uniquely endowed with the means of simultaneously influencing the action potential at the site of origin in groups of pyramidal cells. This strategic location may enable them to synchronise the activity of pyramidal neurons, either through inhibitory gating or through changing the threshold of pyramidal cells to certain inputs.     

Pyramidal cell specialization in the occipitotemporal cortex of the Chacma baboon (<Emphasis Type="Italic">Papio ursinus</Emphasis>)

Pyramidal cell structure varies systematically in occipitotemporal visual areas in monkeys. The dendritic trees of pyramidal cells, on average, become larger, more branched and more spinous with progression from the primary visual area (V1) to the second visual area (V2), the fourth (V4, or dorsolateral DL visual area) and inferotemporal (IT) cortex. Presently available data reveal that the extent of this increase in complexity parallels the expansion of occipitotemporal cortex. Here we extend the basis for comparison by studying pyramidal cell structure in occipitotemporal cortical areas in the chacma baboon. We found a systematic increase in the size of and branching complexity in the basal dendritic trees, as well as a progressive increase in the spine density along the basal dendrites of layer III pyramidal cells through V1, V2 and V4. These data suggest that the trend for more complex pyramidal cells with anterior progression through occipitotemporal visual areas is not a feature restricted to monkeys and prosimians, but is a widespread feature of occipitotemporal cortex in primates.     

Voltage sensitivity of NMDA-receptor mediated postsynaptic currents

Summary The population of neurons in the cat motor cortex which receives monosynaptic input from a specific functional region of the somatic sensory cortex was identified with the techniques of intracellular recording and staining with HRP. Both pyramidal and nonpyramidal cells located in the superficial layers of the pericruciate cortex responded to stimulation of the sensory cortex with short latency, excitatory postsynaptic potentials. More than half of the labeled cells were classified as pyramidal cells and the remainder as sparsely spinous or aspinous nonpyramidal cells. The characteristics of the EPSP's of the 2 groups of cells, ie. latency, time from beginning to peak and amplitude were found to vary only slightly. The results suggest that input from the sensory cortex impinges upon neurons which may in turn have an excitatory or inhibitory effect on corticofugal neurons in the motor cortex.     

Evidence for a neurotropic role of noradrenaline neurons in the postnatal development of rat cerebral cortex

Summary The effects of neonatal administration of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA; 1–4 doses of 100 mg/kg body weight s.c.) on the postnatal development of pyramidal neurons in several cortical regions of the rat was studied using a Golgi-Cox neuronal impregnation technique. Rats were sacrificed in the adult stage (eight weeks) and the following regions were studied: anterior frontal cortex, posterior frontal cortex (including motor cortex), anterior parietal cortex (including sensory cortex), posterior parieto-occipital cortex and cingulate cortex. Significant alterations were seen in animals which received four doses of 6-OHDA. These alterations can be summarized as follows: (1) a decreased length and branching of basolateral dendrites of pyramidal cells, with loss of dendritic spines, which were found in both the internal pyrimidal layer (layer V) and the external pyramidal layer (layer III), most abundantly in the frontal cortex and cingulate cortex; (2) an increased number of pyramidal cells of layer V with premature apical dendritic termination in layer III rather than the usual termination in layers I and II. This was most abundant in the cingulate cortex; (3) occasional disorientation of pyramidal cell apical dendrites away from the normal vertical plane by 15 or more degrees, seen in frontal, parietal and cingulate cortex; (4) an increased number of pyramidal cells with rounded somatic contours, found in frontal, anterior parietal and cingulate cortex. These phenomena were occasionally seen in normal cortex, but were significantly increased in their occurrence after four doses of 6-OHDA. Such alterations were not significant in rats treated with one or three doses of 6-OHDA. The extent and severity of morphological alterations correlate with reductions in endogenous noradrenaline (NA) in cerebral cortex, which was found to average 50% of control levels after one dose of 6-OHDA, an 80% reduction after three doses, and a 97–98% reduction after four doses, suggesting that the NA denervation must be almost complete to result in readily detectable significant morphological changes in the development of cortical pyramidal cells. No consistent changes in endogenous dopamine (DA) levels were observed, except for an increase in the cingulate cortex. The anatomical alterations in pyramidal cells described in the present study suggest that NA neurons which project into the cerebral cortex have a neurotrophic role in the postnatal development of cortex.     

Areal specialization of pyramidal cell structure in the visual cortex of the tree shrew: a new twist revealed in the evolution of cortical circuitry

Cortical pyramidal cells, while having a characteristic morphology, show marked phenotypic variation in primates. Differences have been reported in their size, branching structure and spine density between cortical areas. In particular, there is a systematic increase in the complexity of the structure of pyramidal cells with anterior progression through occipito-temporal cortical visual areas. These differences reflect area-specific specializations in cortical circuitry, which are believed to be important for visual processing. However, it remains unknown as to whether these regional specializations in pyramidal cell structure are restricted to primates. Here we investigated pyramidal cell structure in the visual cortex of the tree shrew, including the primary (V1), second (V2) and temporal dorsal (TD) areas. As in primates, there was a trend for more complex branching structure with anterior progression through visual areas in the tree shrew. However, contrary to the trend reported in primates, cells in the tree shrew tended to become smaller with anterior progression through V1, V2 and TD. In addition, pyramidal cells in V1 of the tree shrew are more than twice as spinous as those in primates. These data suggest that variables that shape the structure of adult cortical pyramidal cells differ among species.     

Specialization in pyramidal cell structure in the sensory-motor cortex of the vervet monkey (Cercopethicus pygerythrus)

Recent studies have revealed systematic differences in the pyramidal cell structure between functionally related cortical areas of primates. Trends for a parallel in pyramidal cell structure and functional complexity have been reported in visual, somatosensory, motor, cingulate and prefrontal cortex in the macaque monkey cortex. These specializations in structure have been interpreted as being fundamental in determining cellular and systems function, endowing circuits in these different cortical areas with different computational power. In the present study we extend our initial finding of systematic specialization of pyramidal cell structure in sensory-motor cortex in the macaque monkey [Cereb Cortex 12 (2002) 1071] to the vervet monkey. More specifically, we investigated pyramidal cell structure in somatosensory and motor areas 1/2, 5, 7, 4 and 6. Neurones in fixed, flat-mounted, cortical slices were injected intracellularly with Lucifer Yellow and processed for a light-stable 3,3'-diaminobenzidine reaction product. The size of, number of branches in, and spine density of the basal dendritic arbors varied systematically such that there was a trend for increasing complexity in arbor structure with progression through 1/2, 5 and 7. In addition, cells in area 6 were larger, more branched, and more spinous than those in area 4.     

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.     

大鼠运动皮层来自胼胝体的同位和异位神经元

实验的目的是用HRP逆行追踪法研究投射至大鼠运动皮层的胼胝体神经元的形态和分布,将HRP注射到大鼠一侧运动皮层后,对侧运动皮层中逆行标记的胼胝体神经元为中等大小的锥体细胞,分布于II／III,V和VI层,其中,V,VI层的细胞较为宽,大;计算机辅助三维重构的图象显示了注射部位和标记部位有很好的对应投射关系。此外,还首次观察到对侧眶回（外侧和腹外侧）向运动皮层的投射。这些位于眶回深层的胼胝体神经元较小而扁,且这种异位起源有投射区域的特异性。仅投向Frl的前端（触须和鼻缘的代表区）,而不向Fr3(爪,唇和舌的代表区）。这些同位和异位胼胝体起源提示了在大鼠的运动功能和其发达的嗅觉之间可能的内在联系。     

Cluster analysis-based physiological classification and morphological properties of inhibitory neurons in layers 2-3 of monkey dorsolateral prefrontal cortex

In primates, little is known about intrinsic electrophysiological properties of neocortical neurons and their morphological correlates. To classify inhibitory cells (interneurons) in layers 2-3 of monkey dorsolateral prefrontal cortex we used whole cell voltage recordings and intracellular labeling in slice preparation with subsequent morphological reconstructions. Regular spiking pyramidal cells have been also included in the sample. Neurons were successfully segregated into three physiological clusters: regular-, intermediate-, and fast-spiking cells using cluster analysis as a multivariate exploratory technique. When morphological types of neurons were mapped on the physiological clusters, the cluster of regular spiking cells contained all pyramidal cells, whereas the intermediate- and fast-spiking clusters consisted exclusively of interneurons. The cluster of fast-spiking cells contained all of the chandelier cells and the majority of local, medium, and wide arbor (basket) interneurons. The cluster of intermediate spiking cells predominantly consisted of cells with the morphology of neurogliaform or vertically oriented (double-bouquet) interneurons. Thus a quantitative approach enabled us to demonstrate that intrinsic electrophysiological properties of neurons in the monkey prefrontal cortex define distinct cell types, which also display distinct morphologies.     

Dendrite bundles in lamina II/III of the rabbit neocortex

Summary The present investigation systematically analyzes the course and arrngement of dendrites in lamina II/III of the visual and the motor cortex of the rabbit on the basis of Klüver-PAS stained 10 m paraffin sections, 1 m plastic-embedded semithin section and ultrathin sections.In both areas the dendritic pattern of lamina II/III is characterized by vertical bundles reminiscent of the pattern in lamina IV/V. The bundles form in the upper half of lamina II/III. They consist mainly of apical dendrites from lamina II/III pyramidal cells and receive branches from dendrite bundles in lamina IV/V, i.e., branches from apical dendrites arising from lamina V pyramidal cells. Besides these features in common, the lamina II/III bundles in the visual cortex on the one hand and in the motor cortex on the other differ with regards to the size and shape of individual bundles as well as to the extent of connections with bundles in lamina IV/V.     

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.     

A fractal analysis of cultured rat optic nerve glial growth and differentiation

Fractal dimension can be used as a quantitative measure of morphological complexity. Separate, enriched populations of oligodendrocytes or type 2 astrocytes derived from neonatal rat optic nerves were allowed to differentiate in vitro. Fractal dimensions of differentiating glial cells were measured over time. The fractal dimension correlated with perceived complexity and increased in value as the glial cells matured. Analysis of the changes in fractal dimension with time revealed unique rates of growth and differentiation for each glial phenotype.     

Morphology of neurons in the white matter of the adult human neocortex

Summary Neurons in the human cerebral cortical white matter below motor, visual, auditory and prefrontal orbital areas have been studied with the Golgi method, immunohistochemistry and diaphorase histochemistry. The majority of white matter neurons are pyramidal cells displaying the typical polarized, spiny dendritic system. The morphological variety includes stellate forms as well as bipolar pyramidal cells, and the expression of a certain morphological phenotype seems to depend on the position of the neuron. Spineless nonpyramidal neurons with multipolar to bitufted dendritic fields constitute less than 10% of the nuerons stained for microtubule associated protein (MAP-2). Only 3% of the MAP-2 immunoreactive neurons display nicotine adenine dinucleotide-diaphorase activity. The white matter pyramidal neurons are arranged in radial rows continuous with the columns of layer VI neurons. Neuron density is highest below layer VI, and decreases with increasing distance from the gray matter. White matter neurons are especially abundant below the primary motor cortex, and are least frequent below the visual cortex area 17. In contrast to other mammalian species, the white matter neurons in man are not only present during development, but persist throughout life.     

Synaptic organization of immunocytochemically identified GABA neurons in the monkey sensory-motor cortex

Neurons in the monkey somatic sensory and motor cortex were labelled immunocytochemically for the GABA synthesizing enzyme, glutamic acid decarboxylase (GAD), and examined with the electron microscope. The somata and dendrites of many large GAD-positive neurons of layers III-VI receive numerous asymmetric synapses from unlabelled terminals and symmetric synapses from GAD-positive terminals. Comparisons with light and electron microscopic studies of Golgi-impregnated neurons suggest that the large labelled neurons are basket cells. Small GAD-positive neurons generally receive few synapses on their somata and dendrites, and probably conform to several morphological types. GAD-positive axons from symmetric synapses on many neuronal elements including the somata, dendrites and initial segments of pyramidal cells, and the somata and dendrites of non-pyramidal cells. Synapses between GAD-positive terminals and GAD-positive cell bodies and dendrites are common in all layers. Many GAD-positive terminals in layers III-VI arise from myelinated axons. Some of the axons form pericellular terminal nests on pyramidal cell somata and are interpreted as originating from basket cells while other GAD-positive myelinated axons synapse with the somata and dendrites of non-pyramidal cells. These findings suggest either that the sites of basket cell terminations are more heterogeneous than previously believed or that there are other classes of GAD-positive neurons with myelinated axons. Unmyelinated GAD-positive axons synapse with the initial segments of pyramidal cell axons or form en passant synapses with dendritic spines and small dendritic shafts and are interpreted as arising from the population of small GAD-positive neurons which appears to include several morphological types.     

The columnar and laminar organization of inhibitory connections to neocortical excitatory cells

The cytoarchitectonic similarities of different neocortical regions have given rise to the idea of 'canonical' connectivity between excitatory neurons of different layers within a column. It is unclear whether similarly general organizational principles also exist for inhibitory neocortical circuits. Here we delineate and compare local inhibitory-to-excitatory wiring patterns in all principal layers of primary motor (M1), somatosensory (S1) and visual (V1) cortex, using genetically targeted photostimulation in a mouse knock-in line that conditionally expresses channelrhodopsin-2 in GABAergic neurons. Inhibitory inputs to excitatory neurons derived largely from the same cortical layer within a three-column diameter. However, subsets of pyramidal cells in layers 2/3 and 5B received extensive translaminar inhibition. These neurons were prominent in V1, where they might correspond to complex cells, less numerous in barrel cortex and absent in M1. Although inhibitory connection patterns were stereotypical, the abundance of individual motifs varied between regions and cells, potentially reflecting functional specializations.