Morphometric analysis of the prefrontal cortex in Huntington's disease

We performed a morphometric analysis of cresyl violet-stained sections from the dorsolateral prefrontal cortex of 81 patients with Huntington's disease (HD) (grades 2, 3, and 4) and 23 age-matched normal controls. We counted large pyramidal neurons, small neurons, astrocytes, oligodendroglia, and microglia under the guidance of a specifically predefined set of morphologic criteria for each cell type and recorded the thickness of each cortical layer. Our results demonstrate a selective and progressive loss of a subset of the large pyramidal neurons in cortical layers III, V, and VI of HD patients, and a decrease in the thickness of the respective cortical laminae. A genetically determined, cell-autonomous degeneration of cortical neurons could constitute the primary pathologic process. However, the loss of only a fraction of pyramidal cells suggest a parallel, or an alternative, possibility of a retrograde degeneration of cortical neurons that project solely, or principally, to the site of primary degeneration in caudate nuclei.     

Primary involvement of the motor area in association with the nigrostriatal pathway in multiple system atrophy: neuropathological and morphometric evaluations

To evaluate the changes that occur in the motor and supplementary motor cortices in cases of multiple system atrophy (MSA), we carried out morphological and morphometric studies in 7 cases of MSA and 11 age-matched controls. Neuropathological study revealed presence of glial cytoplasmic inclusions (GCIs) in the cortex and subcortical white matter of the motor and supplementary motor areas, loss of small to medium-sized pyramidal neurons, and astrocytosis in the motor cortex in all cases of MSA, showing a definite predilection in the cortical layers V and VI. The severity of neuronal loss in the motor cortex was highly correlated with the incidence of GCIs and the involvement of the nigrostriatal pathway. Morphometrically, significant reductions of both the thickness of motor cortical layers V and VI and the number of neurons were observed. In addition, a reduction in the number of neurons in the supplementary motor cortex was detected in three out of the seven MSA cases. The results of this study suggest that the motor area is a cardinal target in MSA, and that in association with the nigrostriatal pathway it forms a motor loop degeneration in this disease.     

Long-term cortical atrophy after excitotoxic striatal lesion: effects of intrastriatal fetal-striatum grafts and implications for Huntington disease

It is not currently clear whether the cortical atrophy observed in Huntington disease (HD) is entirely a direct consequence of the disease or at least partially a secondary consequence of striatal atrophy. This is of major importance for evaluating the possible therapeutic value of intrastriatal fetal-striatum grafts in HD. Cresyl violet-stained sections from rats that had received striatal excitotoxic lesions 1 wk or 4 wk previously showed small and statistically nonsignificant decreases in the thickness of cortical layers V and VI, while series from rats lesioned 12 months previously showed marked decreases in the thickness of the whole cortex (approximately 35% decrease), layer V (approximately 45%-50%) and layer VI (approximately 45%-50%), together with marked neuron loss in these layers. In deep layer V and layer VI, Fluoro-Jade staining showed labeled neurons in animals lesioned 1 wk previously, labeled neurons and astrocytes in animals lesioned 4 wk previously, and practically no labeling in animals lesioned 12 months previously. Intracortical injection of Phaseolus vulgaris leucoagglutinin revealed that corticostriatal fibers were practically absent from the lesioned area of striata lesioned 12 months previously. However, rats that received intrastriatal fetal-striatum grafts shortly after the lesion and were killed 12 months later showed a significant reduction in cortical atrophy, and a large number of labeled corticostriatal fibers surrounding and innervating the graft. In addition, a reduction in the number of Fluoro-Jade-labeled cells in the cortex was already apparent at 3 wk post-grafting. Regardless of whether HD has a primary effect on the cortex, the present results suggest that the striatal degeneration caused by HD contributes markedly to the cortical atrophy, and that intrastriatal grafts may ameliorate this secondary component of the cortical degeneration.     

Ubiquitin and ubiquitin‐related proteins in neurons and dendrites of brains of atypical Pick's disease without Pick bodies

Nine cases of atypical Pick's disease without Pick bodies were investigated immunohistochemically. Ubiquitin (ub)‐positive and tau‐negative structures were mainly found in the cerebral cortex and hippocampal dentate gyrus. In the cerebral cortex, most of the ub‐positive structures had ub‐positive dendrites in the neuropil, although some also showed diffuse ub‐positive staining in the neuronal cytoplasm. These ub‐positive structures were distributed throughout layers II‐IIIab and layers V‐VI. Granular cells of the dentate gyrus had ub‐positive intraneuronal inclusions. When the numbers of ub‐positive neurons and dendrites were evaluated in relation to the degree of neuronal loss in the cerebral cortex, the number of ub‐positive neurons was significantly lower in regions showing very mild neuronal loss and higher in regions showing moderate neuronal loss. In contrast, ub‐positive dendrites were detected even in cortical regions showing very mild neuronal loss. Immunoelectron‐microscopically, ub‐positive structures contained ub‐positive ribosome‐like granular components in the neuronal cytoplasm and dendrites, which were occasionally related to the rough endoplasmic reticulum and accompanied by a few filamentous components. Almost all ub‐positive structures were positive for ub‐binding protein p62 in double‐immunostaining method. Some ub‐positive or negative neurons in the cerebral cortex were positively immunolabeled with anti‐ub ligase (Parkin) and anti‐ub C‐terminal hydrolase antibodies, whereas dendrites were not labeled by these antibodies. From the present study, it is suggested that in the cerebral cortex, these ubiquitinated proteins may firstly accumulate in the dendrites at the onset of neuronal degeneration, then appear in the neuronal cytoplasm before finally disappearing with neuronal loss.     

Cholecystokinin receptors are decreased in basal ganglia and cerebral cortex of Huntington''s disease

Cholecystokinin (CCK) receptors were found to be significantly reduced in basal ganglia and cerebral cortex of post-mortem from Huntington's patients with matched controls. The magnitude of the reduction in CCK binding (69% in basal ganglia, 43% in cerebral cortex) is consistent with the degree of neuronal degeneration in basal ganglia, but suggests a possibly selective loss of CCK receptor-containing neurons in cerebral cortex of Huntington's patients.     

Interlaminar connections of rat visual cortex: An ultrastructural study

Thermal lesions were made in layers I, II, and upper part of layer III of rat visual cortex. The distribution of degenerating axons and axon terminals in layers IV, V, and VI was studied using electron microscopic techniques. Following supragranular thermal lesions, the majority of degenerating axon terminals were found in layer V, with extension into the adjacent part of layer VI. Neural profiles postsynaptic to degenerating axon terminals were found in these layers in the following distribution: 81.7% on spines of small to medium size dendrites; 18.2% on dendrite shafts; and <1% on neuronal perikarya. Few degenerating terminals were found on or near apical dendrites. Degenerating terminals were identified on shafts of stellate-type dendrites found in the upper part of layer V. Degenerating axons oriented parallel to the cortical surface were found most often in deep layer IV and upper layer V. Degenerating axons were also seen in axon bundles coursing vertically through layer IV. Approximately 10% of the terminals within a grid square have undergone degeneration; no clustering of degenerating terminals was found in vertical or transverse sections through layers V and VI. We suggest that most axon terminals arising from pyramidal neurons in layers II and upper III synapse with spines and shafts of dendrite branches originating from pyramidal neurons in layer V and perhaps VI.     

Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics

Quantitative morphometric determinations of neuronal and glial density, neuron-glia ratios, and neuronal size were performed in the prefrontal, anterior cingulate, and primary motor cortex of ten controls and ten schizophrenics diagnosed by Feighner criteria under blind conditions to assess whether neuronal degeneration had occurred. Stepwise multiple regression and multiple classification analyses were used to evaluate the effect of potential confounding variables such as age, postmortem interval, fixation, hypoxia, and neuroleptic exposure on the measures studied. The neuronal density was significantly lower in layer VI of the prefrontal, layer V of the cingulate, and layer III of motor cortex. There was also a trend toward fewer neurons in most layers of both prefrontal and motor cortex, although by discriminant analysis this generalized pattern was significant only for the prefrontal area. The glial density also tended to be lower throughout most layers of all three cortical regions. There were no differences in the neuron-glia ratios or neuronal size between the two groups. The data do not support the presence of neuronal degeneration in schizophrenic cortex as it is conventionally described by neuropathologists, but do suggest the possibility that cytoarchitectural variations in cortical structure might exist in this group of schizophrenics.     

Pyramidal cell loss in motor cortices in Huntington's disease

Patterns of huntingtin protein aggregation and cortical neuronal loss suggest early involvement of corticostriatal pathways in Huntington's disease. However, theories of pathogenesis of chorea rely on the motor cortices being intact. The motor cortices have not previously been studied at a cellular level in Huntington's disease. We analyzed the neuronal number in the caudate, putamen, and three motor cortical areas in five cases of Huntington's disease and five controls. For each motor cortical region the total neuronal number, number of interneurons, and number of SMI32 immunopositive pyramidal neurons were quantified using previously published techniques and any relationship between cell loss and severity or duration of chorea was examined. The results showed a loss of long projecting SMI32 immunopositive pyramidal neurons in the primary motor cortex with associated morphological changes and suggest a loss of short projecting pyramidal neurons in the premotor cortex. Degeneration in the primary motor cortex correlated with subcortical degeneration. These findings indicate pyramidal cell involvement in Huntington's disease and implicate the degeneration of corticostriatal pathways in the production of chorea.     

Oligodendrocyte positioning in cerebral cortex is independent of projection neuron layering

The factors affecting normal oligodendrocyte positioning in the cerebral cortex are unknown. Apart from the white matter, the highest numbers of oligodendrocytes in the rodent cortex are found in Layers V/VI, where the infragranular neurons normally reside. Few, if any, oligodendrocytes are normally found in the superficial cortical layers. To test whether or not this asymmetric positioning of oligodendrocytes is linked to the lamina positions of Layer V/VI projection neurons, mutant mice that cause neuronal layer inversion were examined. In three lines of mutant mice (Reeler, disabled‐1, and p35) examined, representing two different genetic signaling pathways, the oligodendrocyte distribution was altered from an asymmetric to a symmetric distribution pattern. Unlike cortical neurons that are inverted in these mutant mice, the lack of oligodendrocyte inversion suggests a decoupling of the genetic mechanisms governing neuronal versus oligodendrocyte patterning. We conclude that oligodendrocyte positioning is not linked to the layer positions of V/VI projection neurons. © 2008 Wiley‐Liss, Inc.     

Conservation of neuron number and size in entorhinal cortex layers II, III, and V/VI of aged primates

Past dogma asserted that extensive loss of cortical neurons accompanies normal aging. However, recent stereologic studies in humans, monkeys, and rodents have found little evidence of age-related neuronal loss in several cortical regions, including the neocortex and hippocampus. Yet to date, a complete investigation of age-related neuronal loss or size change has not been undertaken in the entorhinal cortex, a retrohippocampal structure essential for learning and memory. The aged rhesus macaque monkey (Macaca mulatta), a species that develops beta-amyloid plaques and exhibits cognitive deficits with age, is considered the best commonly available model of aging in humans. In the present study, we examined changes in total neuron number and size in layers II, III, and V/VI of the intermediate division of the entorhinal cortex in aged vs. nonaged rhesus monkeys by using unbiased stereologic methods. Total neuron number was conserved in aged primates when compared with nonaged adults in entorhinal cortex layer II (aged = 56,500 +/- 12,100, nonaged adult = 48,500 +/- 10,900; P = 0.37), layer III (aged = 205, 600 +/- 50,700, nonaged adult = 187,600 +/- 60,300; P = 0.66), and layers V/VI (aged = 246,400 +/- 76,700, nonaged adult = 236,800 +/- 69,600; P = 0.87). In each of the layers examined, neuronal area and volume were also conserved with aging. This lack of morphologically evident neurodegeneration in primate entorhinal cortex with aging further supports the concept that fundamental differences exist between the processes of normal "healthy" aging and pathologic age-related neurodegenerative disorders such as Alzheimer's disease.     

Early postnatal development of vasoactive intestinal polypeptide- and peptide histidine isoleucine-immunoreactive structures in the cat visual cortex

The early postnatal development of neurons containing vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) has been analyzed in visual areas 17 and 18 of cats aged from postnatal day (P) 0 to adulthood. Neuronal types are established mainly by axonal criteria. Both peptides occur in the same neuronal types and display the same postnatal chronology of appearance. Several cell types are transient, which means that they are present in the cortex only for a limited period of development. According to their chronology of appearance the VIP/PHI-immunoreactive (ir) cell types are grouped into three neuronal populations. The first population comprises six cell types which appear early in postnatal life. The pseudohorsetail cells of layer I possess a vertically descending axon which initially gives rise to recurrent collaterals, then forms a bundle passing layers III to V, and finally, horizontal terminal fibers in layer VI. The neurons differentiate at P 4 and disappear by degeneration around P 30. The neurons with columnar dendritic fields of layers IV/V are characterized by a vertical arrangement of long dendrites ascending or descending parallel to each other, thus forming an up to 600 microns long dendritic column. Their axons always descend and terminate in broad fields in layer VI. The neurons appear at P 7 and are present until P 20. The multipolar neurons of layer VI occur in isolated positions and have broad axonal territories. The neurons differentiate at P 7 and persist into adulthood. Bitufted to multipolar neurons of layers II/III have axons descending as a single fiber to layer VI, where they terminate. The neurons appear at P 12 and persist into adulthood. The four cell types described above issue a vertically oriented fiber architecture in layers II-V and a horizontal terminal plexus in layer VI which is dense during the second, third and fourth week. Concurrent with the disappearance of the two transient types the number of descending axonal bundles and the density of the layer VI plexus is reduced, but the latter is maintained during adulthood by the two persisting cell types. Two further cell types belong to the first population: The transient bipolar cells of layers IV, V, and VI have long dendrites which extend through the entire cortical width. Their axons always descend, leave the gray matter, and apparently terminate in the upper white matter. The neurons differentiate concurrently with the pseudohorsetail cells at P 4, are very frequent during the following weeks, and eventually disappear at P 30.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prenatal development of GABA-immunoreactive neurons in the human striate cortex.

The prenatal development of neurons immunoreactive to gamma-aminobutyric acid (GABA) in the striate cortex (area 17) of human foetuses aged from 14 weeks to term was studied immunocytochemically. In the 14 week foetus GABA-immunoreactive cells occurred in all layers of area 17 with the highest density in the marginal zone (MZ), subplate (SP), deep intermediate zone (IZ) and ventricular zone (VZ). The cortical plate (CP), which gives rise to most of the definitive adult cortical layers, had relatively low concentrations of GABAergic cells. By 17 weeks the density in the proliferative VZ had declined. At 20 weeks some of the adult layers were recognisable; the density of GABA-positive neurons was now highest in the definitive cortex, especially the deep layers (layers VI and V), was lower in the superficial cortical plate, and was lowest in IZ, where the white matter would form. The peak of GABA-immunoreactive neuronal density continued to move superficially during development, and was in layer IVc by 30 weeks. The laminar distribution stabilised from 30 weeks with three dense bands: in layer IVc and superficial V, layer IVa, and layers II and superficial III. The tangential distribution of GABAergic neurons was determined in two older brains (32 and 39 weeks) and no unequivocal spatial periodicity was observed in this plane. The mean cross-sectional area of GABAergic neurons in area 17 increased with foetal age, and also increased from superficial to deep layers at each age. Most GABA-immunoreactive neurons in younger brains contained immunonegative or weakly positive nuclei and had few visible processes, while in the older brains most neurons contained positive nuclei and had more visible processes. The proportion of GABA-immunoreactive bipolar cells declined during development while that of multipolar cells increased. GABAergic neurons thus differentiate early in human foetal striate cortex. They are initially most numerous in the proliferative layers deep to the developing definitive cortex; from 20 weeks of gestation, their peak moves superficially into the maturing deep layers (VI and V) and a stable laminar distribution is attained by 30 weeks, with peaks in layers II/IIIm, IVa and IVc/V. There is no obvious horizontal periodic distribution before term.     

Morphology of neuropeptide Y-immunoreactive neurons and fibers in human prefrontal cortex during prenatal and postnatal development

The subplate and marginal zone are prominent transient zones of the developing cerebral wall and contain a variety of neuropeptide Y-immunoreactive (NPY-ir) cells. This study investigates morphological maturation as well as regression and/or transformation of NPY-ir neurons in the transient compartments and the cortical plate of the human frontal cortex. The most prominent NPY-ir neuronal population is that of NPY-ir subplate neurons. They exhibited features of all subplate neuronal types reported in Golgi-impregnated sections, with the exception of the pyramidal type. The NPY-ir subplate neurons were the largest of all NPY-ir neurons, but their size regressed rather sharply between 1 month after birth and 2 years. In the NPY-ir subplate neurons and in the NPY-ir Cajal-Retzius cells of the marginal zone, signs of degeneration were observed between 36 postovulatory weeks and about 9 months after birth. Only a few subpial granular layer cells were NPY positive, and they exhibited degeneration-like features, such as cytoplasmic vacuolization, as early as 23 postovulatory weeks. However, NPY-ir neurons continued to be present in the adult counterparts of the subplate and marginal zone, i.e., gyral white matter and layer I, respectively. Across cortical layers II-VI, NPY-ir neurons had the hallmarks of all aspinous short-axon types, with the exception of the neurogliaform and the chandelier neuronal types. Some signs of degeneration were also observed among a few cortical NPY-ir neurons around birth. Unlike the NPY-ir subplate neurons, the general development of cortical NPY-ir neurons did not show an obvious decline in neuronal size and was similar to the pattern in Golgi-staining. J. Comp. Neurol. 379:523–540, 1997. © 1997 Wiley-Liss, Inc.     

Comparative effects of adaptation on layers II–III and V–VI neurons in cat V1

V1 is fundamentally grouped into columns that descend from layers II–III to V–VI. Neurons inherent to visual cortex are capable of adapting to changes in the incoming stimuli that drive the cortical plasticity. A principle feature called orientation selectivity can be altered by the presentation of non‐optimal stimulus called ‘adapter’. When triggered, LGN cells impinge upon layer IV and further relay the information to deeper layers via layers II–III. Using different adaptation protocols, neuronal plasticity can be investigated. Superficial neurons in area V1 are well acknowledged to exhibit attraction and repulsion by shifting their tuning peaks when challenged by a non‐optimal stimulus called ‘adapter’. Layers V–VI neurons in spite of partnering layers II–III neurons in cortical computation have not been explored simultaneously toward adaptation. We believe that adaptation not only affects cells specific to a layer but modifies the entire column. In this study, through simultaneous multiunit recordings in anesthetized cats using a multichannel depth electrode, we show for the first time how layers V–VI neurons (1000–1200 μm) along with layers II–III neurons (300–500 μm) exhibit plasticity in response to adaptation. Our results demonstrate that superficial and deeper layer neurons react synonymously toward adapter by exhibiting similar behavioral properties. The neurons displayed similar amplitude of shift and maintained equivalent sharpness of Gaussian tuning peaks before and the following adaptation. It appears that a similar mechanism, belonging to all layers, is responsible for the analog outcome of the neurons’ experience with adapter.     

Expression of the prodynorphin gene in the developing and adult cerebral cortex of the rat: an in situ hybridization study

A population of cortical neurons contains the opioid peptide dynorphin; the laminar distribution of these neurons in the adult cerebral cortex and their patterns of development are not well known. We have utilized in situ hybridization techniques to localize prodynorphin mRNA-containing neurons. Rats aged from embryonic day (E) 15 through postnatal day (P) 90 were used. Prenatal animals did not show any labeling in the cerebral cortex. By P4, prodynorphin was expressed in a small number of cortical neurons for the first time. The autoradiographic signal was restricted to perikarya. In the frontoparietal cortex, labeled neurons first appeared in layer V and the upper part of layer VI. Subsequently, from P11 onward, the band expanded in an "inside-out" sequence to include layers IV through II. In the posterior cingulate cortex and in the insular and perirhinal cortices, prodinorphin mRNA containing-neurons were located preferentially in layer V. In all cortical areas analyzed, a progressive increase in the packing density of neurons expressing prodynorphin mRNA was observed until P14; it decreased slightly thereafter.     

Abnormal neocortical development in mice lacking cGMP-dependent protein kinase I

Cyclic GMP-dependent protein kinase type I (cGKI) is a key signaling intermediate important for synaptic potentiation in the hippocampus and cerebellum, but its expression and function in cortical development have not been elucidated. The expression of cGKI in the developing mouse neocortex was evaluated by immunofluorescence labeling, and effect of cGKI deletion on cortical development was studied in adult cGKI knockout mice. cGKI was expressed at highest levels at embryonic stages in young neurons and radial glial fibers, corresponding to the major period of radial migration and laminar development of pyramidal neurons (embryonic day E13.5-E14.5), declining upon maturation (E17.5-postnatal day P28). The cerebral cortex of homozygous null mutant mice lacking cGKI exhibited heterotopic collections of neurons in the upper cortical layers and abnormal invaginations of layer I, in accord with a neuronal migration or positioning defect. Some cGKI mutant mice displayed defects in midline development resulting in partial fusion of cerebral hemispheres with adjacent neuronal heterotopias. Apical dendrites of cortical pyramidal neurons were misoriented in the cerebral cortex of cGKI null mutants, as shown in reporter mice expressing yellow fluorescent protein in layer V pyramidal neurons and by Golgi impregnation. These results demonstrate a role for cGKI signaling in cortical development related to neuronal migration/positioning that is important for dendritic orientation and connectivity.     

Three classes of pyramidal neurons in layer V of rat perirhinal cortex

Whole-cell recordings from 140 pyramidal neurons in layer V of rat perirhinal cortex (PR) revealed three distinct firing patterns: regular spiking (RS, 76%), burst spiking (BS, 9%), and late spiking (LS, 14%). LS neurons have not previously been reported in layer V of any cortical region. LS cells in layer V of PR exhibited delays of up to 12 s from onset of a depolarizing current step to spike threshold, followed by sustained firing. In contrast, pyramidal cells in layer V of other cortical regions contain only RS and BS cells. Within PR, the percentage of LS neurons in layer V differs markedly from what we previously observed in layers II/III (50% LS) and VI (90% LS). Morphologically, BS neurons in layer V of PR had thick primary apical dendrites that terminated in a tuft within layer I, whereas RS and LS cells had relatively thin primary apicals that terminated either diffusely or in a layer I tuft. At holding potentials near rest, PR neurons exhibited small (approximately 15 pA), inward, spontaneous postsynaptic currents (PSCs) that were indistinguishable among the three cell types. Currents evoked by minimal stimulation of layer I were about 2.8 times larger than the spontaneous PSCs. Evoked currents had unusually long onset latencies with little variation in latency, consistent with monosynaptic responses evoked by stimulation of unmyelinated fibers. The prevalence of LS cells in combination with the long-latency monosynaptically evoked PSCs suggested that PR is not a region of rapid throughput. This is consistent with anatomical data suggesting that PR is a higher-level association cortex. These data further advance an emerging picture of PR as a cortical region with a unique distribution of cell types different from other cortical regions.     

Afferents to Visually Responsive Grafts of Embryonic Occipital Neocortex Tissue Implanted into V1 (Oc1) Cortical Area of Adult Rats

The aim of this study is to determine, as precisely as possible, the topography and the density of host afferents to visually responsive grafts of occipital embryonic cells implanted in block form into the occipital neocortex of adult rats. The presence of visual activity in the grafts was assessed through field potential and single unit electrophysiological recordings. Field potentials appeared triphasic in shape, had low peak-to-peak amplitude (= 100 micro V), and had normal time latencies (? 30 msec). Polarity reversal was never observed. Single unit recordings showed that graft neurons exhibited normal (desynchronized) spontaneous activity, had discrete receptive fields (? 20 masculine in dia.), and responded to small stationary light flashes. A topic projection of the visual field in the grafts was also observed. Injections of cholera toxin sabunit B (CTB) into these responsive grafts induced retrograde labeling in almost all the brain regions normally projecting to the occipital cortical areas. The visual related cortical (Oc 1, Oc2) and thalamic (LP, LD, LGB) regions of the host provide the largest contingent (70-75%) of afferents to the graft. Finally, one of the major findings of this study is that 93-97% of the labeled cortical cells were found in cortical layers V and VI with a net preference for layer VI. A noticeable proportion of these layer VI labeled neurons (15-20%) was systematically observed in sublayer VIb, very close to, or even within, the white matter. We suggest thus that grafts inserted into the occipital cortex of adult rats receive functional visual inputs through various neuronal circuits. Visual inputs could be conveyed to graft eells by: (i) regenerating axons of geniculate neurons previously innervating the injured cortical site; (ii) formation of collateral branches from thalamic axons ending normally in the host cortex close to the graft boundary; and (iii) development of neuronal processes from cells located in the host cortex, mainly in layers V and VI of the occipital areas. Depending on multiple factors, yet unknown but very likely related to the host-graft integration, the cortical circuits might be either the principal afferent inflow to the graft or only a complement to the thalamic input.     

Ubiquitin and ubiquitin‐related proteins in the brains of patients with atypical Pick's disease without Pick bodies and dementia with motor neuron disease

Nine cases of atypical Pick's disease without Pick bodies (aPiD) and seven cases of dementia with motor neuron diseases (D‐MND) were compared using immunohistochemistry of ubiquitin (ub) and ub‐related proteins. All cases showed rostral‐dominant atrophy in the temporal and frontal lobes, although the degree of atrophy with neuronal loss was much more severe in the aPiD cases. In both aPiD and D‐MND cases, ub‐positive and tau‐negative structures were found mainly in the hippocampal dentate gyrus and cerebral cortex. Granular cells of the dentate gyrus showed similar ub‐positive intraneuronal inclusions in both cases. In the aPiD cases, most of the ub‐positive cortical structures were ub‐positive dendrites in layers II‐IIIab and layers V‐VI, although some neurons also showed diffuse ub‐positive staining in the cytoplasm. In the D‐MND cases, some neurons showed ub‐positive inclusions in layers II‐IIIab, and ub‐positive dendrites were unremarkable. The number of ub‐positive neurons and dendrites in relation to the degree of neuronal loss in the cerebral cortex were then evaluated. The number of ub‐positive neurons in the regions showing very mild to mild neuronal loss was significantly greater in the D‐MND cases than in the aPiD cases. However, in the aPiD cases, the number of ub‐positive neurons was significantly greater in the regions showing moderate neuronal loss. When double‐immunostained, almost all ub‐positive structures were positive for ub‐binding protein p62. Some ub‐positive or negative neurons in the cerebral cortex were immunostained with anti‐ub ligase (Parkin) and anti‐ub C‐terminal hydrolase (UCH‐L1) antibodies. Granular cells of the dentate gyrus were weakly positive for UCH‐L1. There could be some differences in the mechanism by which neurons in the cerebral cortex accumulate ub between aPiD and D‐MND.     

Investigations of the origins of transient acetylcholinesterase activity in developing rat visual cortex

Transient acetylcholinesterase (AChE) activity is characteristic of cortical area 17 of the developing laboratory rat during the second and third postnatal weeks of life. This AChE activity is most intense in a band that corresponds to cortical layer IV and the deep part of layer III, but also is found in the outer half of cortical layer I and in layer VI. The morphology of the pattern of the histochemical reaction product indicates that the transient AChE is characteristic of an axonal terminal field. The present report describes results of 3 sets of experiments aimed at determining the source of transient AChE in cortical area 17. First, placement of lesions in portions of the basal forebrain or in the cingulate bundle results in a decrease in the general pattern of AChE throughout occipital cortex and especially in layer I, but the transient bands of AChE in layers III-IV of cortical area 17 are not eliminated. Second, kainic acid or cobalt chloride injections in cortical area 17 result in the loss of many AChE-positive neuronal somata but do not eliminate the transient pattern of AChE in thalamo-recipient layers of cortical area 17. Similarly, treatment of fetuses with mitotic inhibitors that eliminate many of the neurons destined for granular and supragranular layers does not eliminate transient patterns of AChE. Third, lesions that include the lateral geniculate nucleus of the thalamus or geniculocortical projections result in a marked loss of the pattern of AChE in thalamo-recipient layers of cortical area 17, without significant loss in other layers of area 17 or in other regions of occipital cortex. These data support the hypothesis that the transient AChE found in thalamo-recipient layers of cortical area 17 is contained within geniculocortical axon terminals.