Selectivity in the inter-laminar connections made by neocortical neurones

In this brief review of inter-laminar synaptic connections in neocortex a case is made for the hypothesis that axons select their targets, or neurones select their inputs with great specificity. A large part of the data discussed was obtained from dual intracellular recordings in slices of adult neocortex. The neurones innervated in a given layer by a given type of axon were not found to be a random selection of the cells in that layer. Rather in a layer to layer specific fashion, certain types of target cells are densely innervated while others are not contacted or receive only weak inputs. In another layer, the same axons may select other targets.     

The remote consequences of hypoxia influence in perinatal development period on structurally functional characteristics of the rat brain

The study has shown that influence of acute hypoxia in perinatal period leads to structural changes in motor and visual of the neocortex for 20 postnatal days in the form of disturbance of the structural organisation of the neocortex layers. Different fields of hippocampus in perinatal period differently react to hypoxia, and evidence of existence of a long-term perinatal hypoxia was obtained. It is established that after action of acute hypoxia in all the fields there is a cellular destruction, and thinning of pyramidal neurones layers. The most expressed cellular destruction takes place in fields CA4 and CA3. In process of augmentation, the destruction of cells remains appreciable in the field CA4, reduced in the field CA3 and not found in the field CA1; however, in fascia dentate, the destruction of granular neurones with age augmentation increases. Along with in reduction of the dimensions of cellular bodies pyramidal neurones in all fields of hippocampus takes place. Also in all fields of hippocampus, activation of astrocytic reaction occurs, more expressed in the field CA4. The hypoxia influence in the early postnatal period can affect synaptogenes, particularly the formation of giant synapses in a dentate fascia. Study of functional features of the excitatory system of such animals has shown that hypoxia can induce appreciable disturbances of behavioural responses. In rats, disturbances of inhibiting functions of the cerebral cortex, raised anxiety, and spatial learning and working memory disturbances have been noted.     

Changes in glutamate dehydrogenase activity in the neurons of the motor cortexof the cerebral hemispheres during light deprivation

It has been shown that early light deprivation (keeping the rats for eight weeks from birth in a dark chamber) produces compensatory changes in the majority of pyramidal neurones in layers III and V of the brain motor area: significant enhancement of glutamatdehydrogenase activity activity in the bodies and processes of the neurones, increase of their volumes, augmentation of the number of neuroglial satellites with a high ferment activity. The revealed morphochemical changes, more pronounced in the layer V, are considered as a manifestation of enhanced functional activity of the coritcal end of the motor analyser, resulting from visual dereceptation.     

Non-associative Potentiation of Perisomatic Inhibition Alters the Temporal Coding of Neocortical Layer 5 Pyramidal Neurons

In the neocortex, the coexistence of temporally locked excitation and inhibition governs complex network activity underlying cognitive functions, and is believed to be altered in several brain diseases. Here we show that this equilibrium can be unlocked by increased activity of layer 5 pyramidal neurons of the mouse neocortex. Somatic depolarization or short bursts of action potentials of layer 5 pyramidal neurons induced a selective long-term potentiation of GABAergic synapses (LTPi) without affecting glutamatergic inputs. Remarkably, LTPi was selective for perisomatic inhibition from parvalbumin basket cells, leaving dendritic inhibition intact. It relied on retrograde signaling of nitric oxide, which persistently altered presynaptic GABA release and diffused to inhibitory synapses impinging on adjacent pyramidal neurons. LTPi reduced the time window of synaptic summation and increased the temporal precision of spike generation. Thus, increases in single cortical pyramidal neuron activity can induce an interneuron-selective GABAergic plasticity effectively altering the computation of temporally coded information.     

Comparative distribution of acid phosphatase and simple esterase in the mouse neocortex and hippocampal formation

The present study deals with the detailed distribution of acid phosphatase (AcP) and simple esterase (SE) in different layers of the neocortex and hippocampal formation of the mouse brain. The neurons, in general, had moderate to intense enzyme activity for AcP and mild to moderate activity for SE. The AcP activity dominated in the neuronal population as compared to the neuropil; the neuropil stained mildly for SE. The large pyramidal cells in the neocortex and cornu ammonis, and the granular cell layer of the gyrus dentatus, demonstrated strong enzyme activity both in AcP and SE preparations. The role of AcP and SE has been discussed in relation to various structures of the neocortex and hippocampal formation.     

Structure of the neocortex of the Baikal ringed seal (Pusa sibirica Gm.)]

The sulci and gyri of the neocortex, as well as cyto-, synaptoarchitectonics and neuronal composition of the sensomotor (brain area) have been studied in the Baikal ringed seal. The structure of the sulci and gyri have been found to be similar to that in carnivores. The following specific features have been revealed in the brain of this endemic species: a thick layer I, presence of giant pyramidal cells in the layer III, large mitochondria in the presynaptic parts and dendrites. The results obtained are discussed concerning adaptation to semiaqueous way of life and to diving.     

Spatial organization and interneuronal relations in various areas of the neocortex in Cetacea

The data on pyramidal neurons joining in the parietal and temporal areas of the dolphin neocortex by means of apical dendrites fasciculi are presented. The fasciculi also contain dendrites of spindle-like and stellate cells. The vertical fasciculi of the dendrites unite neurons of the layer V and of the sublayer III2. In the sublayer III1, after dichotonic division of the apical dendrites, fasciculi of the second order are formed, to them the dendrites of the pyramidal neurons of the sublayer III1 and the layer II join. Several forms of the interneuronal contacts have been revealed: axo-dendritic, axo-spinous and dendro-dendritic. Synaptic complexes of the converged and divergent types have been shown. A suggestion is made on formation of larger neuronal modules++, having common afferent entrance and demonstrating selectivity to the stimulus properties.     

Spatial organization and interrelation of structural elements of the 1st layer of the neocortex

Investigating topography and structure of elements in the layer I of the fields 4, 3, 1 of the human neocortex (4 cases) and M1, Ep zones in the cat neocortex (5 cases) by means of modified methods of Golgi, Peters and Kluver-Barerr, it became possible to work out an original classification of astrocytes and to reveal the neurono-glio-vascular complexes consisting of the neuronal base and two glial-vascular links. Three main varieties of protoplasmic astrocytes are determined: short-rayed with a long dendrite-like process, short-rayed cap-like and long-rayed with a double bush of branchings. In the latter forms axon-like processes are revealed, some of them make complex basket-like branchings and each of them surrounds a group of neuronal bodies, predominantly the pyramidal ones in the layer III. Distribution of the marginal glia and the three mentioned varieties of astrocytes is subjected to a single plan. The raws of gliocytes along the horizontal and vertical lines are connected with each other and with the neuronal elements. Peculiar receptive apparatuses performing interrelation are ball-like formations revealed on the apical dendrites of the pyramidal neurons. The information that gets into them is processed automatically. Problems concerning the importance of the ball-like formations in integration of the layer I is discussed, and the role of the glial cells with axon-like processes in the active transport of various substances and in regulating metabolism of the pyramidal cells of the layer III is also dealt with.     

Cortical integration in the visual system of the macaque monkey: large-scale morphological differences in the pyramidal neurons in the occipital, parietal and temporal lobes.

Layer III pyramidal neurons were injected with Lucifer yellow in tangential cortical slices taken from the inferior temporal cortex (area TE) and the superior temporal polysensory (STP) area of the macaque monkey. Basal dendritic field areas of layer III pyramidal neurons in area STP are significantly larger, and their dendritic arborizations more complex, than those of cells in area TE. Moreover, the dendritic fields of layer III pyramidal neurons in both STP and TE are many times larger and more complex than those in areas forming 'lower' stages in cortical visual processing, such as the first (V1), second (V2), fourth (V4) and middle temporal (MT) visual areas. By combining data on spine density with those of Sholl analyses, we were able to estimate the average number of spines in the basal dendritic field of layer III pyramidal neurons in each area. These calculations revealed a 13-fold difference in the number of spines in the basal dendritic field between areas STP and V1 in animals of similar age. The large differences in complexity of the same kind of neuron in different visual areas go against arguments for isopotentiality of different cortical regions and provide a basis that allows pyramidal neurons in temporal areas TE and STP to integrate more inputs than neurons in more caudal visual areas.     

The early postnatal nonhuman primate neocortex contains self-renewing multipotent neural progenitor cells

The postnatal neocortex has traditionally been considered a non-neurogenic region, under non-pathological conditions. A few studies suggest, however, that a small subpopulation of neural cells born during postnatal life can differentiate into neurons that take up residence within the neocortex, implying that postnatal neurogenesis could occur in this region, albeit at a low level. Evidence to support this hypothesis remains controversial while the source of putative neural progenitors responsible for generating new neurons in the postnatal neocortex is unknown. Here we report the identification of self-renewing multipotent neural progenitor cells (NPCs) derived from the postnatal day 14 (PD14) marmoset monkey primary visual cortex (V1, striate cortex). While neuronal maturation within V1 is well advanced by PD14, we observed cells throughout this region that co-expressed Sox2 and Ki67, defining a population of resident proliferating progenitor cells. When cultured at low density in the presence of epidermal growth factor (EGF) and/or fibroblast growth factor 2 (FGF-2), dissociated V1 tissue gave rise to multipotent neurospheres that exhibited the ability to differentiate into neurons, oligodendrocytes and astrocytes. While the capacity to generate neurones and oligodendrocytes was not observed beyond the third passage, astrocyte-restricted neurospheres could be maintained for up to 6 passages. This study provides the first direct evidence for the existence of multipotent NPCs within the postnatal neocortex of the nonhuman primate. The potential contribution of neocortical NPCs to neural repair following injury raises exciting new possibilities for the field of regenerative medicine.     

Ageing of the human entorhinal cortex and subicular complex.

Age-dependent changes in the entorhinal cortex (EC) and subicular complex (SC) were studied in 30 brains of patients who died between 14 and 86 years of age, without CNS impairment, as determined by macro- and microscopic examination. The brains were fixed in 10% formalin and embedded in paraffin. Three series of coronal EC and SC sections (7 microns) were stained by Nissl, PAS or hematoxylin-eosin. Using neuronal count and Kariometry, age-dependent modifications were studied in layers II, III and V of the lateral area of the EC; in the pyramidal layer of the subiculum (S), and in layer II of the presubiculum (PS). All EC layers studied presented a slight (11-20%) although significant reduction up to 35 years, but from 35 to 75 years the decrease was not significant. After 75 years the neuronal loss increased slightly. The nuclear area decreased up to the age of 40-45 years, (10-18%) and augmented from this age up to 75 years (10-14%). During the last period of life, the nuclear area did not change. From 30-60 years, pyramidal layer in the S showed a significant neuronal loss (30%), thereafter, neuronal reduction was less. At early years, the nuclear area decreased insignificantly (15%), and from 35 years up to the most advanced age studied, it increased significantly (13%). In the PS, layer II manifested a cell loss throughout the lifespan (32.9%) and the changes in the nuclear area did not reach statistical significance due to the dispersions of its values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neural recognition molecules CHL1 and NB-3 regulate apical dendrite orientation in the neocortex via PTP alpha

Apical dendrites of pyramidal neurons in the neocortex have a stereotypic orientation that is important for neuronal function. Neural recognition molecule Close Homolog of L1 (CHL1) has been shown to regulate oriented growth of apical dendrites in the mouse caudal cortex. Here we show that CHL1 directly associates with NB-3, a member of the F3/contactin family of neural recognition molecules, and enhances its cell surface expression. Similar to CHL1, NB-3 exhibits high-caudal to low-rostral expression in the deep layer neurons of the neocortex. NB-3-deficient mice show abnormal apical dendrite projections of deep layer pyramidal neurons in the visual cortex. Both CHL1 and NB-3 interact with protein tyrosine phosphatase alpha (PTPalpha) and regulate its activity. Moreover, deep layer pyramidal neurons of PTPalpha-deficient mice develop misoriented, even inverted, apical dendrites. We propose a signaling complex in which PTPalpha mediates CHL1 and NB-3-regulated apical dendrite projection in the developing caudal cortex.     

Cytoarchitectonics of the cerebral cortex in mice selected for high and low brain weight

The cortex cytoarchitectonics was studied in mice, which had been genetically selected for high (H-line) and low (L-line) brain weight and manifested some differences in their behaviour. Microscopic brain sections were analysed to estimate the areas of the neocortex, archicortex and paleocortex and to investigate quantitatively the microstructure in different zones of the neocortex. In the H-line, absolute value of total cortical area is, on the average, by 18% higher than that in the L-line--mainly owing to the larger area of neocortex, while the mean values of neurone volume fraction and profile field reveal no significant difference between the H- and L-line. Hence, the total number of neurones in the neocortex of mice from H-line should be greater, as compared with the L-line. Besides, within the framework of the same cerebral organization in general, the obtained data are indicative of a somewhat higher spatial differentiation of the neocortex in mice from the H-line.     

Loss of glutaminase-positive cortical neurons in Alzheimer's disease

Phosphate activated glutaminase (PAG) was evaluated in the neocortex of Alzheimer and control cases. Consistent with previously reported results in rat cerebral cortex, pyramidal cells were stained immunohistochemically by a PAG specific polyclonal rabbit antibody, especially in layers II, III and V. An Alzheimer's case showed drastic depletion of PAG-positive pyramidal neurons, especially in layers II and III. Cortical PAG levels by biochemical assay were reduced to 18% of control in a small series of Alzheimer's cases (n=3), while choline acetyltransferase (ChAT) was reduced to 28% of control in the same tissue samples. PAG staining was also observed in large neurons of the rat neostriatum. Double immunostaining for PAG and ChAT established that these large neurons also contained both enzymes.Special issue dedicated to Dr. Elling Kvamme     

Structure of the fetal sheep brain in experimental growth retardation

A quantitative morphometric study of brain development has been made in growth-retarded fetal sheep. Intrauterine growth retardation was induced by removal of endometrial caruncles in the ewe prior to conception thereby reducing the size of the placenta in a subsequent pregnancy. Total brain and cerebellar weights were reduced by 21% (P less than 0.002) and the cerebrum by 20% (P less than 0.05) in the growth-retarded fetuses at 139 +/- 1 day (term = 146 days) compared with age matched control fetuses. Measurements of mean neuronal diameters were made on Purkinje cells, cerebellar granule cells, cortical cells in the motor and visual areas and hippocampal pyramidal cells; none were significantly different from control values. In growth-retarded fetuses compared with controls, there was a significant reduction in the thickness of the motor and visual cortices and the numerical density of neurones was significantly higher in these areas. In the cerebellar vermis, the number of Purkinje cells per unit surface area of Purkinje cell layer was higher, the numerical density of granule cells was significantly higher concomitant with a reduction in the area of the inner granular layer, and the area of the molecular layer was also reduced. In the hippocampal formation, the numerical density of pyramidal neurones was higher and the width of the stratum moleculare (dentate gyrus) was reduced. Migration of pyramidal neurones from the germinal layer to stratum pyramidale was not affected. These findings indicate that intrauterine growth retardation does not markedly affect cell size or neuronal migration (in the hippocampus) but does cause a significant reduction in the growth of the neuropil in the cerebellum, motor and visual cortices and the hippocampal formation.     

Biochemical Evidence of Selective Nerve Cell Changes in the Normal Ageing Human and Rat Brain

Abstract: Atrophy with ageing of human whole brain, entire temporal lobe, and caudate nucleus was assessed in autopsy specimens, by biochemical techniques. Only the caudate nucleus showed changes. Markers for several neurotransmitter systems were also examined for changes with age. In neocortex and temporal lobe of human brain, small decreases were detected in markers of cholinergic nerve terminals, whereas a large decrease (79%) occurred in the caudate nucleus. Findings were similar in striatum from 3–33-month-old rats. No change occurred in binding of [³H]quinuclidinyl benzilate by human samples. Markers of serotonergic terminals were also unchanged in human and rat brain. By contrast, binding of [³H]lysergic acid diethylamide and [³H]serotonin was decreased (32–81%) in human neocortex and temporal lobe, but not in caudate nucleus. A 43% loss of a marker of γ-aminobutyrate terminals occurred in human neocortex, while [³H]muscimol binding increased (179%). No changes were detected in markers of catecholamine synapses in temporal lobe or rat striatum. Hence, with human ageing there appears to be a loss of markers of γ-aminobutyrate neurones intrinsic to neocortex and acetylcholine cells intrinsic to the caudate nucleus, as well as a change in postsynaptic serotonin receptors in neocortex. These losses are accompanied by relative preservation of markers of ascending projections from basal forebrain and brain stem.     

IP3-dependent calcium-induced calcium release mediates bidirectional calcium waves in neurones: functional implications for synaptic plasticity

IP(3)-dependent calcium-induced calcium release (ICICR) is a general mechanism of calcium release that occurs in pyramidal neurones of hippocampus, the neocortex and in Purkinje cells of the cerebellar cortex. When ICICR is initiated synaptically in dendrites of neurones from brain slices, calcium waves can propagate bidirectionally to the soma and distal dendrites. ICICR relies on the coincidence of a calcium influx triggered by the backpropagation of action potentials and the activation of cholinergic, serotoninergic or glutamatergic metabotropic receptors. The involvement of IP(3) receptors (IP(3)R) in ICICR is clearly established. In contrast, ryanodine receptors (RyR) do not seem necessary for the triggering and propagation of calcium waves, but ICICR depends on calcium stores sensitive to ryanodine. Thus, the role of RyR remains to be established. ICICR provides a mechanism for global calcium signalling in neurones that may be involved in the reinforcement of Hebbian plasticity, heterosynaptic plasticity and cell death.     

An embedded subnetwork of highly active neurons in the neocortex

Unbiased methods to assess the firing activity of individual neurons in the neocortex have revealed that a large proportion of cells fire at extremely low rates (<0.1 Hz), both in their spontaneous and evoked activity. Thus, firing in neocortical networks appears to be dominated by a small population of highly active neurons. Here, we use a fosGFP transgenic mouse to examine the properties of cells with a recent history of elevated activity. FosGFP-expressing layer 2/3 pyramidal cells fired at higher rates compared to fosGFP(-) neurons, both in vivo and in vitro. Elevated activity could be attributed to increased excitatory and decreased inhibitory drive to fosGFP(+) neurons. Paired-cell recordings indicated that fosGFP(+) neurons had a greater likelihood of being connected to each other. These findings indicate that highly active, interconnected neuronal ensembles are present in the neocortex and suggest these cells may play a role in the encoding of sensory information. VIDEO ABSTRACT:     

Exploitation of the HIV-1 coat glycoprotein, gp120, in neurodegenerative studies in vivo

Neuronal loss has often been described at post-mortem in the brain neocortex of patients suffering from AIDS. Neuroinvasive strains of HIV infect macrophages, microglial cells and multinucleated giant cells, but not neurones. Processing of the virus by cells of the myelomonocytic lineage yields viral products that, in conjunction with potentially neurotoxic molecules generated by the host, might initiate a complex network of events which lead neurones to death. In particular, the HIV-1 coat glycoprotein, gp120, has been proposed as a likely aetiologic agent of the described neuronal loss because it causes death of neurones in culture. More recently, it has been shown that brain neocortical cell death is caused in rat by intracerebroventricular injection of a recombinant gp120 coat protein, and that this occurs via apoptosis. The latter observation broadens our knowledge in the pathophysiology of the reported neuronal cell loss and opens a new lane of experimental research for the development of novel therapeutic strategies to limit damage to the brain of patients suffering from HIV-associated dementia.