Differential distribution of parvalbumin-immunoreactive pericellular clusters of terminal boutons in developing and adult monkey neocortex.

Basket cells are GABAergic inhibitory interneurons and known regulators of pyramidal cells, the major class of excitatory neurons in neocortex. Parvalbumin (PV), a calcium binding protein, has been colocalized with GABA in cortical neurons (Celio, 1986. Science 231: 995-998) and has been reported to be present in the terminal boutons of basket neurons forming pericellular clusters in monkey neocortex (Hendry et al. 1989. Exp. Brain Res. 76: 467-472). In this study, we used immunohistochemical methods to evaluate the regional and laminar distributions of PV-immunoreactive (PV-IR) pericellular clusters of terminal boutons in the neocortex of neonatal, infant, adolescent, and adult rhesus monkeys. PV-IR pericellular clusters were composed of labeled terminal boutons that outlined the somata and proximal dendrites of large pyramidal neurons in layers III and V of primary motor cortex, layers V and VI of primary visual cortex, and layer V of visual association cortex (area 18). This laminar pattern was present in neonatal animals and did not change with age in motor cortex. However, in the visual regions of adolescent and adult animals, such PV-IR structures were not detected. PV-positive pericellular clusters were not observed in the prefrontal cortex at any age. The pattern of distribution of PV-containing pericellular clusters paralleled that of a subpopulation of pyramidal neurons containing nonphosphorylated neurofilament proteins (NFP); double labeling studies confirmed that a subgroup of NFP-positive pyramidal neurons were the targets of PV-IR pericellular clusters. The distribution of PV-IR pericellular clusters was compared to that of PV-IR terminal boutons of another class of interneurons, the chandelier cells. Terminal boutons of chandelier neuron axons align in vertical rod-like structures known as cartridges. Subpopulations of chandelier axon cartridges have been previously shown to be PV-IR and their distribution in visual and prefrontal cortices has been described (DeFelipe et al. 1989. Brain Res. 503: 49-54; Lewis and Lund. 1990. J. Comp. Neurol. 293: 599-615). These two types of structures composed of PV-IR terminal boutons tended to be present in different laminae in all regions and ages examined, except in layer III of primary motor cortex where both PV-IR pericellular clusters and chandelier cartridges were found. These findings indicate that in monkey neocortex PV immunoreactivity is present in pericellular clusters of terminal boutons that are likely to arise from basket cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

Immunocytochemical localization of glutamate-, glutaminase- and aspartate aminotransferase-like immunoreactivity in the rat deep cerebellar nuclei

Although the anatomy and the connectivity of the deep cerebellar nuclei have been well documented, little is known about the neurotransmitter systems mediating cerebellar efferent pathways. The present study utilizes immunohistochemical procedures in conjunction with a novel monoclonal antibody specific for carbodiimide-fixed glutamate and polyclonal antisera against glutaminase (GLNase) and aspartate aminotransferase (AATase) to examine the presence of putative excitatory amino acid transmitters in neurons of the deep cerebellar nuclei. Carbodiimide-fixed glutamate-like, GLNase-like and AATase-like immunoreactivities were observed in neurons of the lateral, posterior interpositus, anterior interpositus and medial deep cerebellar nuclei. More neurons were stained with AATase antiserum than with the GLNase antiserum or the monoclonal antibody. These results suggest glutamate, GLNase and AATase are present in neurons of the deep cerebellar nuclei and raise the possibility that glutamate may be an excitatory transmitter in these structures.     

Distribution and morphological characterization of phosphate-activated glutaminase-immunoreactive neurons in cat visual cortex

Phosphate-activated glutaminase (PAG) is the major enzyme involved in the synthesis of the excitatory neurotransmitter glutamate in cortical neurons of the mammalian cerebral cortex. In this study, the distribution and morphology of glutamatergic neurons in cat visual cortex was monitored through immunocytochemistry for PAG. We first determined the specificity of the anti-rat brain PAG polyclonal antibody for cat brain PAG. We then examined the laminar expression profile and the phenotype of PAG-immunopositive neurons in area 17 and 18 of cat visual cortex. Neuronal cell bodies with moderate to intense PAG immunoreactivity were distributed throughout cortical layers II-VI and near the border with the white matter of both visual areas. The largest and most intensely labeled cells were mainly restricted to cortical layers III and V. Careful examination of the typology of PAG-immunoreactive cells based on the size and shape of the cell body together with the dendritic pattern indicated that the vast majority of these cells were pyramidal neurons. However, PAG immunoreactivity was also observed in a paucity of non-pyramidal neurons in cortical layers IV and VI of both visual areas. To further characterize the PAG-immunopositive neuronal population we performed double-stainings between PAG and three calcium-binding proteins, parvalbumin, calbindin and calretinin, to determine whether GABAergic non-pyramidal cells can express PAG, and neurofilament protein, a marker for a subset of pyramidal neurons in mammalian neocortex. We here present PAG as a neurochemical marker to map excitatory cortical neurons that use the amino acid glutamate as their neurotransmitter in cat visual cortex.     

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

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

Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease: II. Primary and secondary visual cortex.

In this study we investigated the primary and secondary visual areas of normal and Alzheimer's disease brains by using the SMI32 antibody. It is known that in Alzheimer's disease primary sensory areas are usually less devastated than association cortices, although visual symptomatology has been documented early in the course of the disease. In area 17, the SMI32 antibody primarily labeled the perikarya and dentritic tree of the large Meynert cells and cells in layer IVB. Smaller neurons in layers III, V, and VI were also immunoreactive (ir). In area 18, very large SMI32-ir pyramidal neurons in layers III and V were observed. In both areas, staining intensity was correlated with cell size, the largest neurons being the most intensely stained. Only a few changes were observed in the Alzheimer's disease cases. The only statistically significant differences in SMI32-ir neuron counts between control and Alzheimer's disease brains occurred in layer IVB cells and Meynert cells in area 17, and in layer III cells in area 18. In contrast with association cortices, there were no changes in staining intensity in the visual areas. There were fewer neurofibrillary tangles and neuritic plaques in these areas than in prefrontal and inferior temporal cortex, and a correlation between neurofibrillary tangle counts and SMI32-ir neuron loss was only observed in layer III of area 18. These observations show that in the primary and secondary visual cortex, SMI32 also labeled a distinct subset of pyramidal cells that are known from data obtained in the monkey brain to furnish long corticocortical as well as subcortical projections. Interestingly, although there is much less cell and/or neurofibrillary tangle formation in these occipital regions than in prefrontal and temporal association areas, there is significant loss within key subsets of pyramidal cells. The selective loss of this particular subpopulation of pyramidal neurons will disrupt association pathways linking primary visual cortex with areas involved in higher level visual processing. The partial disconnection of such pathways may be relevant to the visual symptomatology frequently observed in Alzheimer's disease patients. These data further support the hypothesis that subtypes of pyramidal neurons with specific anatomical and molecular profiles may display a differential vulnerability in Alzheimer's disease.     

Excitatory transmitter amino acid-containing neurons in the rat visual cortex: a light and electron microscopic immunocytochemical study

The distribution and morphology of neurons labelled with antisera to glutamate or aspartate were examined, at the light and electron microscope levels, in the rat visual cortex. Using widely accepted light microscopic features as well as well-established nuclear, cytoplasmic, and synaptic criteria, we noted that glutamate-immunoreactive neurons were pyramidal cells distributed in layers II-VI, with an increased concentration in layers II and III. Aspartate immunoreactivity was localized chiefly to pyramidal neurons in layers II-VI. However, approximately 10% of immunolabeled cells were nonpyramidal neurons scattered throughout the cortex. Cell-body measurements revealed that, for both groups of neurons, layer V contained the largest labelled neurons, whereas layers IV and VI contained the smallest. Furthermore, in every layer, aspartate-stained neurons were larger than glutamate-positive cells. Finally, glutamate- and aspartate-labelled axon terminals formed asymmetrical synapses, which are presumably excitatory in nature, primarily with dendritic spines. These findings, together with recent detailed studies of the projections of glutamate- and aspartate-labelled cortical neurons, may provide essential background information for studies aimed to elucidate the function(s) of excitatory amino acids in the cortex and their role in pathological conditions.     

Immunohistochemical localization of a membrane-associated, 4.1-like protein in the rat visual cortex during postnatal development

Expression and localization of a membrane-associated protein, an analog of erythrocyte protein 4.1, in the visual cortex were immunohistochemically studied in the rat, ranging in age from newborn to adult. In the adult, dendrites and somas of layer V pyramidal cells were stained by the antiprotein 4.1 antibody. In most of these immunoreactive neurons, the plasma membrane seemed to be preferentially stained. Neurons located in layers II and III of the cortex were only faintly stained, and those in layers IV and VI were not stained. At birth, the immunoreactivity was already present in 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 the 4.1-like protein is expressed only in the neurons that have differentiated or are differentiating. At postnatal days 2-8, immunoreactive neurons were dramatically increased in layers V and VI and intense labeling was seen at the apical dendrites of layer V pyramidal cells. Most of the stained processes of these and other neurons showed a sign of rapid dendritic growth, i.e., growth cones and filopidia. At days 10-17, the basal dendrites of pyramidal cells in layers II and III became detectable, although still slender. At days 20-37, these dendrites in layers II, III, and V became intensely immunoreactive, and dendritic spines were visualized by the antibody. Throughout all the ages, axons of neurons and neuroglia were not stained by the antibody. Also, most of the neurons in layer IV of the cortex were not immunoreactive. These results suggest that the 4.1-like protein is abundantly expressed in growing parts of the dendrites and spines. A hypothesis that this protein may play a role in synaptic plasticity in the developing visual cortex is discussed.     

Antibody to a soluble protein purified from brain selectively labels layer V corticofugal projection neurons in rat neocortex

An antibody to a soluble protein (protein 36) isolated and purified from rat brain labels the cell bodies and processes of pyramidal cells within layer V of the rat neocortex. We have used the fluorescent retrograde axonal tracer, Fast blue, in combination with FITC immunocytochemistry to determine the projection sites of the cortical neurons detected by this antibody. Retrogradely labeled pyramidal tract neurons and corticotectal neurons are labeled with the protein 36 antibody, but the callosally projecting neurons within layer V are not. Thus within the neocortex the antibody to protein 36 may selectively detect a particular class of neuron, the corticofugal projection neurons of layer V.     

Corticotropin-releasing factor immunoreactivity in monkey neocortex: an immunohistochemical analysis

Corticotropin-releasing factor (CRF) has been implicated in the pathophysiology of certain human neuropsychiatric disorders that affect neocortical function. However, the anatomical organization of CRF-containing structures in the expanded and highly differentiated primate neocortex has not been previously described. In this study, the distribution of CRF-immunoreactive neurons and processes was characterized in the neocortex of New World squirrel monkeys (Saimiri sciureus). Substantial regional differences were present in the density, laminar distribution, and morphological appearance of CRF-immunoreactive neurons. The greatest density of labeled neurons was present in anterior cingulate cortex. A wide range of intermediate densities of CRF-immunoreactive neurons was evident in the association regions of the prefrontal, parietal, and temporal cortices. The lowest numbers of CRF-immunoreactive neurons were observed in the primary visual and primary motor cortices. For example, the density of labeled neurons was nearly five times greater in the anterior cingulate cortex than in the precentral cortex. CRF-immunoreactive neurons were also distributed in at least four different laminar patterns. For example, in the agranular anterior cingulate cortex, labeled cell bodies were distributed throughout layers II, III, and V. In other regions, such as the posterior cingulate cortex, labeled neurons were present in layers II, III, and IV. In contrast, labeled neurons were predominantly present in layers II and superficial III of the visual cortex, whereas in the inferior temporal cortex, they were present predominantly in layer IV. Regional and laminar differences were also present in the relative distributions of the two major morphological types (as defined by cell body shape) of CRF-immunoreactive neurons. Vertically oriented oval neurons, which frequently had a single dendritic process arising from each somal pole, were most frequently found in layer III. In contrast, the labeled neurons in layers II and IV tended to have a round- or triangular-shaped soma. In layer IV of some association cortices, these multipolar neurons were associated with a high density of rod-like structures composed of large immunoreactive varicosities clustered together in vertical arrays. These structures were frequently found to be located immediately below the soma of pyramidal neurons. Comparison of these findings with Golgi impregnation studies strongly suggests that CRF is present in the soma and axonal cartridges of a subset of chandelier neurons. The heterogeneous distribution and morphological diversity of CRF-containing neurons suggest that CRF may mediate distinct functions in different regions and layers of monkey neocortex.     

Columnar organization of dendrites and axons of single and synaptically coupled excitatory spiny neurons in layer 4 of the rat barrel cortex.

Cortical columns are the functional units of the neocortex that are particularly prominent in the "barrel" field of the somatosensory cortex. Here we describe the morphology of two classes of synaptically coupled excitatory neurons in layer 4 of the barrel cortex, spiny stellate, and star pyramidal cells, respectively. Within a single barrel, their somata tend to be organized in clusters. The dendritic arbors are largely confined to layer 4, except for the distal part of the apical dendrite of star pyramidal neurons that extends into layer 2/3. In contrast, the axon of both types of neurons spans the cortex from layer 1 to layer 6. The most prominent axonal projections are those to layers 4 and 2/3 where they are largely restricted to a single cortical column. In layers 5 and 6, a small fraction of axon collaterals projects also across cortical columns. Consistent with the dense axonal projection to layers 4 and 2/3, the total number and density of boutons per unit axonal length was also highest there. Electron microscopy combined with GABA postimmunogold labeling revealed that most (>90%) of the synaptic contacts were established on dendritic spines and shafts of excitatory neurons in layers 4 and 2/3. The largely columnar organization of dendrites and axons of both cell types, combined with the preferential and dense projections within cortical layers 4 and 2/3, suggests that spiny stellate and star pyramidal neurons of layer 4 serve to amplify thalamic input and relay excitation vertically within a single cortical column.     

Organization of pyramidal neurons in area 17 of monkey visual cortex.

In sections of area 17 of monkey visual cortex treated with an antibody to MAP2 the disposition of the cell bodies and dendrites of the neurons is readily visible. In such preparations it is evident that the apical dendrites of the pyramidal cells of layer VI form fascicles that pass into layer IV, where most of them gradually taper and form their terminal tufts. In contrast, the apical dendrites of the smaller layer V pyramidal cells come together in a more regular fashion. They form clusters that pass through layer IV and into layer II/III where the apical dendrites of many of the pyramidal cells in that layer add to the clusters. In horizontal sections taken through the middle of layer IV, these clusters of apical dendrites are found to have an average center-to-center spacing of about 30 microns, and it is proposed that each cluster of apical dendrites represents the axis of a module of pyramidal cells that has a diameter of about 30 microns and contains about 142 neurons. The MAP2 antibody reaction also reveals that some pyramidal cells in layers IVA and IVB have their cell bodies arranged into cones. There are about 118 such cones beneath 1 mm2 of cortical surface and the apical dendrites of the pyramidal cells within them bundle together at the apex of each cone to pass into layer III. Surrounding the cones of neurons there are horizontally aligned, thin dendrites. The location of these dendrites coincides with the dark walls of the honeycomb pattern seen in layer IVA after cytochrome oxidase reactions, or after the parvocellular input from the lateral geniculate nucleus has been labeled. Thus the cones of pyramidal cells within upper layer IV fit into the pockets of the honeycomb pattern. Below the cones of pyramidal cells are the outer Meynert cells within layer IVB, and the cell bodies of these large neurons are disposed so that they preferentially lie beneath the neuropil between the cones of pyramids. It is suggested that pyramidal cell modules are a basic feature of the cerebral cortex, and that these are combined together by afferent inputs to the cortex to generate the systems of functional columns.     

Immunolocalisation of protein phosphatase inhibitor-1 in the cerebral cortex of the rat, cat and ferret

The distribution of inhibitor-1 was analysed in the neocortex of cat, ferret and rat by immunocytochemistry (at the light and electron microscope levels) and by immunoblotting using an affinity purified antibody which recognises both the phosphorylated and dephosphorylated forms of the protein. In each mammalian cortex immunocytochemical techniques identified inhibitor-1 predominantly in infragranular pyramidal neurons and, at a lower concentration, in supragranular pyramidal neurons of cortical layers II–III, and V–VI. Within the cortical layers, neuronal cell bodies and apical dendrites were stained strongly but no immunoreactivity was associated with dendritic spines. Regional differences in intensity of staining were revealed when appropriate antibody concentrations were used; the concentration of inhibitor-1 appeared to follow a gradient with the highest levels in layer VI and the lowest in layer I. The results were confirmed by immunoblotting of microdissected cortical regions which identified the inhibitor-1 protein unambiguously. The distribution of inhibitor-1 is different from that reported by other investigators.     

Sprouting of sympathetic fibers in the hippocampus in the absence of major target cell candidates

The distribution and morphology of functionally identified neurons were examined in the visual cortex of Long Evans pigmented rats. The results, based on qualitative and quantitative analysis of single cell spike activity, have shown that neurons in the rat visual cortex have well-defined receptive field properties and are similar to those reported for animals with more highly developed visual systems. Unlike the cat and monkey, the distribution of receptive field types appeared even throughout the visual cortex. Exception was provided by layer IV which, similar to the more 'visual' animals, contained the largest percentage of simple cells. Horseradish peroxidase injected into single, physiologically identified neurons allowed for detailed morphological characterization of functional cell types. Of the cells successfully filled with horseradish peroxidase, complex cells were pyramidal in morphology and located in layers II through VI. Simple cells were both pyramidal and non-pyramidal in appearance and were located in layers II + III and IV. Finally, hypercomplex cells were pyramidal in appearance and their perikarya were situated in layers II + III and V.     

Distribution of phosphate-activated glutaminase in the human cerebral cortex

Phosphate-activated glutaminase (PAG), which catalyses conversion of glutamine to glutamate, is a potential marker for glutamatergic, and possibly GABA, neurons in the central nervous system. A polyclonal antibody, raised in rabbits against rat brain PAG, was applied to postmortem human brain tissue to reveal the distribution of PAG in the cerebral cortex. PAG immunoreactivity was observed in pyramidal and non-pyramidal neurons but not in glial cells. In the neocortex, large to medium-sized pyramidal neurons in layers III and V were stained most intensely, while the majority of smaller pyramidal cells were labeled either lightly or moderately. Such modified pyramids as the giant Betz cells, the large pyramidal cells of Meynert, and the solitary cells of Ramón y Cajal were also stained intensely. Fusiform cells in layer VI showed moderate to intense labeling. A number of cortical non-pyramidal neurons of various sizes stained moderately to intensely. These included large basket cells which were identified by their characteristic morphology and size in primary cortical areas. Pyramidal cells in the hippocampal formation as well as basket cells of the stratum oriens stained moderately to intensely. Since pyramidal cells are believed to be glutamatergic and large basket cells GABAergic, these results suggest that PAG plays a role in generating not only transmitter glutamate, but also GABA precursor glutamate.     

Regional heterogeneity in the distribution of somatostatin-28- and somatostatin-28(1-12)-immunoreactive profiles in monkey neocortex

The distribution of the prosomatostatin-derived peptides (PSDP), somatostatin-28 and somatostatin-28(1-12), in the cynomolgus monkey (Macaca fascicularis) neocortex was characterized in quantitative immunohistochemical studies of 3 visual areas (V1, primary visual cortex; V2, the adjacent visual association area; and AIT, a visual association area in anterior inferior temporal cortex), 2 auditory areas (AI, primary auditory cortex; and T1, an adjacent auditory association area) and anterior cingulate cortex (Area 24). The results of similar quantitative analyses in 3 homologous areas in rat neocortex (primary visual, primary auditory, and anterior cingulate) are also presented. Primate cortical areas differed significantly in both density and laminar distribution of PSDP-immunoreactive profiles. Area 24, the most densely labeled area, had nearly 6 times as many PSDP-immunoreactive neurons as V1. Both auditory areas contained approximately two-thirds the number of PSDP-immunoreactive neurons found in Area 24; however, both had nearly 4 times as many immunoreactive neurons as V1. The 3 visual areas showed incremental increases in the number of PSDP-immunoreactive neurons; V2 contained nearly twice and AIT nearly 3 times the number of immunoreactive neurons present in V1. Both the supra- and infragranular layers were densely labeled in Area 24 and Area T1, however, in AI, V1, V2, and AIT the infragranular layers were relatively sparsely labeled. In contrast to the regional heterogeneity found in the primate neocortex, the distribution of immunoreactive neurons was quite uniform across the 3 rat cortical areas. The rat cortical areas contained substantially fewer immunoreactive neurons than most of the monkey cortical areas, and a majority of these immunoreactive neurons were located in the infragranular layers. These findings suggest that the regional specialization of primate neocortex involves the selective distribution of PSDP-immunoreactive neurons. They also suggest that chemically specified intrinsic organization of neocortex is not likely to be uniform across species or across cortical areas in the primate. The distinctive regional distribution patterns of PSDP-immunoreactive profiles appear to parallel that of the long corticocortical projections (contralateral and distant ipsilateral projections), suggesting an association between these presumed inhibitory interneurons and this important extrinsic system.     

Dendritic branching angles of pyramidal cells across layers of the juvenile rat somatosensory cortex

The characterization of the structural design of cortical microcircuits is essential for understanding how they contribute to function in both health and disease. Since pyramidal neurons represent the most abundant neuronal type and their dendritic spines constitute the major postsynaptic elements of cortical excitatory synapses, our understanding of the synaptic organization of the neocortex largely depends on the available knowledge regarding the structure of pyramidal cells. Previous studies have identified several apparently common rules in dendritic geometry. We study the dendritic branching angles of pyramidal cells across layers to further shed light on the principles that determine the geometric shapes of these cells. We find that the dendritic branching angles of pyramidal cells from layers II–VI of the juvenile rat somatosensory cortex suggest common design principles, despite the particular morphological and functional features that are characteristic of pyramidal cells in each cortical layer. J. Comp. Neurol. 524:2567–2576, 2016. © 2016 Wiley Periodicals, Inc.     

Dendritic morphology, local circuitry, and intrinsic electrophysiology of principal neurons in the entorhinal cortex of macaque monkeys

Little is known about the neuroanatomical or electrophysiological properties of individual neurons in the primate entorhinal cortex. We have used intracellular recording and biocytin-labeling techniques in the entorhinal slice preparation from macaque monkeys to investigate the morphology and intrinsic electrophysiology of principal neurons. These neurons have previously been studied most extensively in rats. In monkeys, layer II neurons are usually stellate cells, as in rats, but they occasionally have a pyramidal shape. They tend to discharge trains, not bursts, of action potentials, and some display subthreshold membrane potential oscillations. Layer III neurons are pyramidal, and they do not appear to display membrane potential oscillations. The distribution of dendrites and of axon collaterals suggests that neurons in layers II and III are interconnected by a network of associational fibers. Layer V and VI neurons are pyramidal and tend to discharge trains of action potentials. The distribution of dendrites and axon collaterals suggests that there is an associative network of principal neurons in layers V and VI, and they also project axon collaterals toward superficial layers. Importantly, entorhinal cortical neurons in monkeys appear to exhibit significant differences from those in rats. Morphologically, neurons in monkey entorhinal layers II and III have more primary dendrites, more dendritic branches, and greater total dendritic length than in rats. Electrophysiologically, layer II neurons in monkeys exhibit less sag, and subthreshold oscillations are less robust and slower. Some monkey layer III neurons discharge bursts of action potentials that are not found in rats. The interspecies differences revealed by this study may influence information processing and pathophysiological processes in the primate entorhinal cortex. J. Comp. Neurol. 470:317-329, 2004.     

Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual and auditory cortices

The number of Thioflavine S-positive neurofibrillary tangles (NFT) and neuritic plaques (NP) was determined in visual and auditory cortical regions of 8 patients with Alzheimer's disease. On both a regional and laminar basis, NFT exhibited very distinctive and consistent distribution patterns. The mean (+/- SEM) number of NFT in a 250-micron-wide cortical traverse was very low in area 17, primary visual cortex (0.9 +/- 1.0), increased 20-fold in the immediately adjacent visual association cortex of area 18 (19.7 +/- 3.6), and showed a further doubling in area 20, the higher-order visual association cortex of the inferior temporal gyrus (35.5 +/- 8.8). Similar differences in NFT number were present between primary auditory (1.6 +/- 0.5) and auditory association (18.9 +/- 5.4) regions. On a laminar basis, NFT were predominantly present in layers III and V, although there were striking regional differences in the proportion of NFT in these 2 layers. Layer III contained 79% of the NFT in layers III and V in area 18, 41% in area 20, and only 27% in area 22. In contrast, NP showed different, and less specific, regional and laminar distribution patterns. Total NP number was similar in the 3 visual areas, although there were marked regional differences in the type of NP present. Nearly 80% of the NP in area 17 was of the NPc type (i.e., contained a dense, brightly fluorescent core), whereas over 70% of the NP in both areas 18 and 21 was of the NPnc type (i.e., lacked a dense, brightly fluorescent core). NP were present in every cortical layer but were most numerous in layers III and IV. The distinctive distribution patterns of NFT are very similar to the regional and laminar locations of long corticocortical projection neurons in homologous regions of monkey neocortex. This association suggests that NFT reside in the cell bodies of a subpopulation of pyramidal neurons, namely, those that furnish long corticocortical projections. In contrast, the distribution patterns of NP suggest that multiple neuronal systems contribute to their formation.     

I-wave origin and modulation

The human motor cortex can be activated by transcranial magnetic stimulation (TMS) evoking a high-frequency repetitive discharge of corticospinal neurones. The exact physiologic mechanisms producing the corticospinal activity still remain unclear because of the complexity of the interactions between the currents induced in the brain and the circuits of cerebral cortex, composed of multiple excitatory and inhibitory neurons and axons of different size, location, orientation and function. The aim of current paper is to evaluate whether the main characteristics of the activity evoked by single- and paired-pulse and repetitive TMS, can be accounted by the interaction of the induced currents in the brain with the key anatomic features of a simple cortical circuit composed of the superficial population of excitatory pyramidal neurons of layers II and III, the large pyramidal neurons in layer V, and the inhibitory GABA cells. This circuit represents the minimum architecture necessary for capturing the most essential cortical input-output operations of neocortex. The interaction between the induced currents in the brain and this simple model of cortical circuitry might explain the characteristics and nature of the repetitive discharge evoked by TMS, including its regular and rhythmic nature and its dose-dependency and pharmacologic modulation. The integrative properties of the circuit also provide a good framework for the interpretation of the changes in the cortical output produced by paired and repetitive TMS.