New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors

Ongoing neurogenesis in the adult mammalian dentate gyrus and olfactory bulb is generally accepted, but its existence in other adult brain regions is highly controversial. We labeled newly born cells in adult rats with the S-phase marker bromodeoxyuridine (BrdU) and used neuronal markers to characterize new cells at different time points after cell division. In the neocortex and striatum, we found BrdU-labeled cells that expressed each of the eight neuronal markers. Their size as well as staining for gamma-aminobutyric acid (GABA), glutamic acid decarboxylase 67, calretinin and/or calbindin, suggest that new neurons in both regions are GABAergic interneurons. BrdU and doublecortin-immunoreactive (BrdU+/DCX+) cells were seen within the striatum, suggesting migration of immature neurons from the subventricular zone. Surprisingly, no DCX+ cells were found within the neocortex. NG2 immunoreactivity in some new neocortical neurons suggested that they may instead be generated from the NG2+ precursors that reside within the cortex itself.     

Olfactory bulb axonal outgrowth is inhibited by draxin

Olfactory bulb (OB) projection neurons receive sensory input from olfactory receptor neurons and precisely relay it through their axons to the olfactory cortex. Thus, olfactory bulb axonal tracts play an important role in relaying information to the higher order of olfactory structures in the brain. Several classes of axon guidance molecules influence the pathfinding of the olfactory bulb axons. Draxin, a recently identified novel class of repulsive axon guidance protein, is essential for the formation of forebrain commissures and can mediate repulsion of diverse classes of neurons from chickens and mice. In this study, we have investigated the draxin expression pattern in the mouse telencephalon and its guidance functions for OB axonal projection to the telencephalon. We have found that draxin is expressed in the neocortex and septum at E13 and E17.5 when OB projection neurons form the lateral olfactory tract (LOT) rostrocaudally along the ventrolateral side of the telencephalon. Draxin inhibits axonal outgrowth from olfactory bulb explants in vitro and draxin-binding activity in the LOT axons in vivo is detected. The LOT develops normally in draxin−/− mice despite subtle defasciculation in the tract of these mutants. These results suggest that draxin functions as an inhibitory guidance cue for OB axons and indicate its contribution to the formation of the LOT.     

Light microscopy of the medial wall of the cerebral cortex of the lizard Psammodromus algirus

The telencephalic medial wall of the lizard Psammodromus algirus was studied using Golgi and conventional light microscopic techniques. The area is formed by two different cytological fields—medial cortex and dorsomedial cortex. These two cortices possess three layers dorsoventrally: a superficial plexiform layer, a cellular layer, and a deep plexiform layer. The alveus, a deep fiber system, runs adjacent to the ependyma. Four classes of neurons are found in the cellular layer of the medial cortex on the basis of soma shape, dendritic pattern, and position in the layer: horizontal, double pyramidal, and candelabra cells. Solitary cells are present in the superficial and deep plexiform layers of the medial cortex. Those of the superficial plexiform layer are stellate cells. Horizontal and vertical cells are found in the deep plexiform layer. Double pyramidal cells are the most frequently impregnated in the cellular layer of the dorsomedial cortex. In addition, candelabra cells are present at the lateral end of the layer. Two cell types are found in the deep plexiform layer of the dorsomedial cortex: solitary pyramidal cells and, among the fibers of the alveus, horizontal cells. Ependymal tanycytes line the ventricular surface, and protoplasmic astrocytes are found in the plexiform layers of both medial and dorsomedial cortices.     

Differential encoding of behavior and spatial context in deep and superficial layers of the neocortex

Rodent hippocampal activity is correlated with spatial and behavioral context, but how context affects coding in association neocortex is not well understood. The cellular distribution of the neural activity-regulated immediate-early gene Arc was used to monitor the activity history of cells in CA1, and in deep and superficial layers of posterior parietal and gustatory cortices (which encode movement and taste, respectively), during two behavioral epochs in which spatial and behavioral context were independently manipulated while gustatory input was held constant. Under conditions in which the hippocampus strongly differentiated behavioral and spatial contexts, deep parietal and gustatory layers did not discriminate between spatial contexts, whereas superficial layers in both neocortical regions discriminated well. Deep parietal cells discriminated behavioral context, whereas deep gustatory cortex neurons encoded the two conditions identically. Increased context sensitivity of superficial neocortical layers, which receive more hippocampal outflow, may reflect a general principle of neocortical organization for memory retrieval.     

Determination of cell fate within the telencephalon

The telencephalon (basal ganglia, septum, cerebral cortex and olfactory bulb) contains two general classes of neurons: those that project axons to distant targets and those that make only local connections. While projection neurons can be either excitatory (such as those in the olfactory bulb and cortex) or inhibitory (such as those in the striatum), local circuit neurons (interneurons) are usually inhibitory. Within these two general classes of neurons there are a myriad of cell subtypes based upon axonal and dendritic morphology, chemical markers, neurotransmitters, connectivity and physiology. A crucial issue regarding the development of the telencephalon is the molecular determination of neuronal subtypes. Since important aspects of neuronal fate determination occur within the proliferative zone, the consideration of determinants of a mature neuron's fate requires consideration of that cell's origin.     

A major role for intracortical circuits in the strength and tuning of odor-evoked excitation in olfactory cortex

In primary sensory cortices, there are two main sources of excitation: afferent sensory input relayed from the periphery and recurrent intracortical input. Untangling the functional roles of these two excitatory pathways is fundamental for understanding how cortical neurons process sensory stimuli. Odor representations in the primary olfactory (piriform) cortex depend on excitatory sensory afferents from the olfactory bulb. However, piriform cortex pyramidal cells also receive dense intracortical excitatory connections, and the relative contribution of these two pathways to odor responses is unclear. Using a combination of in vivo whole-cell voltage-clamp recording and selective synaptic silencing, we show that the recruitment of intracortical input, rather than olfactory bulb input, largely determines the strength of odor-evoked excitatory synaptic transmission in rat piriform cortical neurons. Furthermore, we find that intracortical synapses dominate odor-evoked excitatory transmission in broadly tuned neurons, whereas bulbar synapses dominate excitatory synaptic responses in more narrowly tuned neurons.     

Neuronal lineages in chimeric mouse forebrain are segregated between compartments and in the rostrocaudal and radial planes

On the basis of neuronal phenotypes and the mode of development of the mammalian forebrain, the cerebral cortex can be subdivided into deep versus superficial layers, and the striatum into patch versus matrix compartments. Interspecific chimeric Mus musculus----Mus caroli mice were used to determine the contribution of lineage to cellular position within these forebrain compartments. Statistical analysis revealed evidence of both spatial and compartmental lineage segregation. A significant difference in genotype ratio depending on chimeric specimen was observed between areas (regardless of compartment) that were separated by greater than 300 microns in the rostrocaudal plane. Differences were observed between early-born (striatal patch and deep cortex) versus late-born (striatal matrix and superficial cortex) neurons, but not between neurons of cortex as a whole versus neurons of striatum as a whole. The difference between early- and late-born neurons was primarily due to the difference between deep and superficial cortical neurons. On a finer scale of analysis, differences in genotype ratios were seen between radially aligned deep versus superficial cortical compartments, in both the neuronal and glial populations. This evidence is consistent with an early positional and compartmental segregation of forebrain progenitor cells.     

Olfactory predictive codes and stimulus templates in piriform cortex

Neuroscientific models of sensory perception suggest that the brain utilizes predictive codes in advance of a stimulus encounter, enabling organisms to infer forthcoming sensory events. However, it is poorly understood how such mechanisms are implemented in the olfactory system. Combining high-resolution functional magnetic resonance imaging with multivariate (pattern-based) analyses, we examined the spatiotemporal evolution of odor perception in the human brain during an olfactory search task. Ensemble activity patterns in anterior piriform cortex (APC) and orbitofrontal cortex (OFC) reflected the attended odor target both before and after stimulus onset. In contrast, prestimulus ensemble representations of the odor target in posterior piriform cortex (PPC) gave way to poststimulus representations of the odor itself. Critically, the robustness of target-related patterns in PPC predicted subsequent behavioral performance. Our findings directly show that the brain generates predictive templates or "search images" in PPC, with physical correspondence to odor-specific pattern representations, to augment olfactory perception.     

Non-pyramidal neurons of layers I-III in the dog's cerebral cortex (parietal lobe). A Golgi survey

In an attempt to classify neurons in the upper layers of the cerebral cortex according to modern nomenclature based on Golgi impregnations, non-pyramidal neurons in layers II and III of the dog's cerebral cortex have been categorized into thirteen types: large double-bouquet cells with long ascending and descending axons (type I double-bouquet cells); bipolar neurons; multipolar neurons with long tufted descending axons (type II double-bouquet cells); neurons with long ascending axons; neurons with superficial axon plexuses; elongated large multipolar neurons with extended generalized axonal arborizations; neurons with long descending axons; small bi-tufted neurons with short ascending, descending or local axons; small multipolar neurons with short ascending, descending or local axons; multipolar neurons with local or extended axonal arborizations usually forming arcades (some of them also with a long descending axon); basket cells; neurogliaform neurons, and chandelier cells. Neurons in the molecular layer were horizontal cells and multipolar neurons with short axons. These data have been compared with those described in other species to provide a provisional classification of non-pyramidal neurons located in the upper layers of the cerebral cortex.     

Intrinsic organization of the medial cerebral cortex of the lizard Lacerta pityusensis: A golgi study

The morphology of cells and the organization of axons were studied in Golgi-Colonnier and toluidine blue stained preparations from the medial cerebral cortex of the lizard Lacerta pityusensis. In the medial cortex, six strata were distinguished between the superficial glial membrane and the ependyma. Strata I and II formed the outer plexiform layer, stratum III formed the cellular layer, and strata IV go VI the inner plexiform layer. The outer plexiform layer contained smooth bipolar neurons; their dendrites were oriented anteroposteriorly and their axons were directed towards the posterior zone of the brain. Five neuronal types were observed in the cellular layer. The spinous pyramidal neurons had well-developed apical dendrites and poorly developed basal ones. Their axons entered the inner plexiform layer and gave off collaterals oriented anteroposteriorly. The small, sparsely spinous pyramidal neurons had poorly developed dendrites and their axons entered the inner plexiform layer. The spinous bitufted neurons had well-developed apical and basal dendritic tufts. Their axons gave off collaterals that reached the outer and inner plexiform layers of both the dorsomedial and dorsal cortices. The sparsely spinous horizontal neurons had dendrites restricted to the outer plexiform layer. Their axons entered the inner plexiform layer. The sparsely spinous, multipolar neurons had their soma close to stratum IV and their axons entered the outer plexiform layer. In stratum V of the inner plexiform layer were large, spiny polymorphic neurons; they had dendrites with long spines, and their axons reached the cellular layer. On the basis of these results, we have subdivided the medial cortex into two subregions: the superficial region, which contains the neurons of the cellular layer and their dendritic domains, and the deep region, strata V and VI, which contains the large, spiny polymorphic neurons. The neurons in the medial cortex of these lizards resembles those in the area dentata of mammals. On this basis, the superficial region may be compared to the dentate gyrus and the deep region to the hilar region of the hippocampus of mammals.     

Exposure to behaviourally relevant odour reveals differential characteristics in rat central olfactory pathways as studied through oscillatory activities

This study investigated how changes in nutritional motivation modulate odour-related oscillatory activities at several levels of the olfactory pathway in non-trained rats. Local field potential recordings were obtained in freely moving animals in the olfactory bulb (OB), anterior and posterior parts of the piriform cortex (APC and PPC respectively) and lateral entorhinal cortex (EC). Dynamic signal analysis detected changes in power during odour presentation for several frequency bands The results showed that in most cases odour presentation was associated with changes in a wide 15-90 Hz frequency band of activity in each olfactory structure. However, nutritional state modulated initial responses to food odour (FO) in the OB and EC selectively in the 15-30 Hz frequency band. Changes in nutritional state also modulated responses to repeated FO stimuli. Habituation was expressed differentially across structures with a clear dissociation between the two parts of the piriform cortex. Finally, systemic injections of scopolamine (0.125 mg/kg) selectively blocked expression of the nutritional modulation in the OB found in the beta band. These results suggest that internal state can differentially modulate odour processing among different olfactory areas and point to a cholinergic-sensitive beta band oscillation during presentation of a behaviourally meaningful odorant.     

Ontogeny of Neurochemical Markers for Noradrenergic, GABAergic and Cholinergic Neurons in Neocortex Lesioned with Methylazoxymethanol Acetate

Abstract: Methylazoxymethanol acetate (MAM), a potent, rapidly eliminated nucleic acid alkylating agent, produces microencephaly in rat pups when injected into their dams on day 15 of gestation. In the adult microencephalic rats, neuronal loss is largely confined to telencephalic structures, such as the superficial neocortical laminae, whose neuroepithelial progenitor cells were undergoing vigorous replication during the chemical exposure. Histological examination of the forebrain 2 days after injection revealed early selective damage to the ventricular geminal zone with relative sparing of cortical plate neurons generated on earlier days. The degree of specificity of MAM's action on neurochemically defined neuronal populations was examined by measuring presynaptic markers for GABAergic, noradrenergic and cholinergic neurons in atrophic lateral cortex from 20 days gestation to adulthood. Although treatment reduced GABAergic markers (GABA, its synthetic enzyme and synaptosomal uptake process) in proportion to loss of cortex mass (-67%), the maturational pattern for remaining GABAergic neurons was virtually normal. Although the maturational sequence of noradrenergic markers was similar to control, the concentration of endogenous norepinephrine, [³H]norepinephrine uptake and tyrosine hydroxylase specific activity were two- to fourfold higher than control at each time. However, total noradrenergic markers per cortex section were nearly identical to control throughout development, indicating that development of the noradrenergic axonal arbor in neocortex was insensitive to loss of neurons in the terminal field. Maturation of cholinergic markers (endogenous acetylcholine, its synthetic enzyme and [³H]choline uptake) in the atrophic cortex was biphasic: concentrations were similar to control values for the first 12 postnatal days, but gradually rose to levels twofold higher than control. These results indicate that neurochemical alterations observed in cortex from prenatally MAM-treated rats are primarily the result of early selective elimination of neuronal subpopulations. Fetal MAM exposure appeared to have minimal effects on biochemical differentiation of neurons remaining intact in the atrophic cortex. MAM appears to be a useful toxin for producing selective loss of neuronal groups based on their time of generation in the fetus.     

Persistence of Cajal-Retzius cells in the adult human cerebral cortex. An immunohistochemical study

The presence of Cajal-Retzius cells in the adult human prefrontal and visual cortices has been demonstrated with calcium binding protein immunocytochemistry and NADPH-diaphorase histochemistry. These cells expressed parvalbumin, calbindin and calretinin calcium binding proteins and displayed NADPH-diaphorase enzyme activity. The three basic morphological profiles-horizontal, pyriform and multipolar-were observed. The morphologies of labelled cells resembled those of neurons observed in Golgi studies of the human cerebral cortex. The presence of calcium binding proteins and NADPH-diaphorase in these cells suggests a possible inhibitory role as GABAergic neurons. The persistence of Cajal-Retzius cells in the adult cerebral cortex supports the idea that they undergo developmental dilution rather than postnatal degeneration.     

Beyond the primary olfactory cortex: olfactory-related areas in the neocortex, thalamus and hypothalamus

The extrinsic projections from the primary olfactory cortexto other areas of the forebrain in the rat are described, onthe basis of experiments using anterograde and retrograde axonaltracers, as well as electrophysiological recording of unit activity.The areas shown to receive olfactory inputs are (i) in the neocortex:the lateral and ventrolateral orbital areas, and the ventralagranular insular area, all of which are in the dorsal bankof the rhinal sulcus; (ii) in the thalamus: the central segmentof the mediodorsal nucleus and the ventral part of the submedicalnucleus; (iii) in the hypothalamus: the lateral hypothalamicarea, especially its caudal half, and probably the nucleus gemiru,with some input also to more medial hypothalamic structures;(iv) the hippocampus and dentate gyrus; and (v) the deep nucleiof the amygdala. Anterograde and retrograde axonal tracing experimentshave shown that all of these areas receive fibers from cellsin or closely related to the primary olfactory cortex, and cellsin all of them except the nucleus gemini and the deep nucleiof the amygdala have been shown to be driven by electrical stimulationof the olfactory bulb.     

Neural Precursor Cells from Adult Mouse Cerebral Cortex Differentiate into Both Neurons and Oligodendrocytes

Recent findings concerning adult neurogenesis in two selected structures of the mammalian brain, the olfactory bulb and dentate gyrus of the hippocampus, present the possibility that this mechanism of neurogenesis applies for all brain regions, including the cerebral neocortex. In this way, a small number of potential neural precursor cells may exist in the cerebral neocortex, but they do not normally differentiate into cortical neurons in vivo. It has, however, been reported recently that cycling cells isolated from non-neurogenic areas of adult rat cerebral cortex could generate neurons in vitro. In this study, we analyzed the lineage potential of cycling cells from the adult mouse neocortex. For the dissection of the cerebral cortex from the adult mouse, which is significantly smaller than that of the adult rat, we have modified the previous dissection protocol developed for the rat neocortex. As a result, cycling cells from adult mouse neocortex gave rise to neurons and oligodendrocytes, but not to astrocytes, whereas when the previous dissection method was used, cycling cells gave rise to neurons, oligodendrocytes and astrocytes. This discrepancy might stem from slight contamination of the dissected mouse neocortical tissue in the previous protocol used for the dissection of rat neocortex by cells from the surrounding subependymal zone, where typical adult neural stem cells exist. The results presented here will contribute to our understanding of the nature of cycling cells in the adult mammalian neocortex, and for which future stem cell research will provide new possibilities for cell replacement therapy to be used in the treatment of neurodegenerative conditions.     

Expression of the small conductance Ca<Superscript>2+</Superscript>-activated K<Superscript>+</Superscript> channel,SK3, in the olfactory ensheathing glial cells of rat brain

Olfactory sensory neurons are wrapped by ensheathing glial cells in the olfactory nerve layer (ONL). Neither functional roles nor electrical properties of ensheathing glial cells have been, as yet, fully clarified. Four subunits (SK1–4) of small conductance Ca²⁺-activated K⁺ (SK) channels have been cloned. In the present study, immunohistochemical analyses showed that SK3 channels are expressed in ensheathing glial cells in the rat olfactory bulb, in addition to neuronal cells in other regions. Western blotting analysis demonstrated that SK3 was predominantly expressed in the olfactory bulb, thalamus, moderately in the hippocampus and cerebellum and modestly in the cerebral cortex of the rat brain. SK3 immunoreactivity was detected in the ONL of the olfactory bulb, neural cell body and fibers of the substantia nigra and hypothalamus. SK3 immunoreactivity was quite intense in the outer (superficial) part of the ONL. SK3-immunoreactive structures were overlapped with glial fibrillary acidic protein (GFAP), but not with vimentin, markers for glial cells and olfactory sensory axons, respectively. Immunoelectron microscopy showed that SK3 immunoreactivity was localized in thin processes that enfolded fascicles of immunonegative olfactory nerve axons. These results indicate that SK3 is expressed specifically in the olfactory ensheathing glial cells in olfactory regions.This work was supported in part by a Grant-in-Aid to A.F. for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan, and by scholarship from Ono Pharmaceutical Company, and by Narishige Neuroscience Research Foundation.     

阿尔茨海默病嗅觉障碍研究进展

阿尔茨海默病(Alzheimer’s disease,AD)患者在出现认知功能障碍之前,普遍表现出嗅觉相关功能障碍,而且嗅觉系统病变程度与AD进展密切相关。因此,嗅觉系统功能障碍可能成为早期诊断AD及评价其进展的指标。近几年通过对AD患者和AD转基因动物模型的研究发现,嗅觉系统可能是AD退行性病变的始发部位,而且具有从外周向中枢发展的趋势,即病变首先发生于嗅觉系统的近外周部分(嗅上皮、嗅球等),然后发展至嗅皮层(梨状皮层、内嗅皮层等),进而累及海马和新皮层区等。此外,AD病理改变的这种时空模式与嗅觉相关行为障碍、神经通路及递质的改变等具有很高的相关性。重点综述了以上方面的研究结果。     

Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation.

The levels of nerve growth factor (NGF) and its mRNA in the rat central nervous system were determined by two-site enzyme immunoassay and quantitative Northern blots, respectively. Relatively high NGF levels (0.4-1.4 ng NGF/g wet weight) were found both in the regions innervated by the magnocellular cholinergic neurons of the basal forebrain (hippocampus, olfactory bulb, neocortex) and in the regions containing the cell bodies of these neurons (septum, nucleus of the diagonal band of Broca, nucleus basalis of Meynert). Comparatively low, but significant NGF levels (0.07-0.21 ng NGF/g wet weight) were found in various other brain regions. mRNANGF was found in the hippocampus and cortex but not in the septum. This suggests that magnocellular cholinergic neurons of the basal forebrain are supplied with NGF via retrograde axonal transport from their fields of innervation. These results, taken together with those of previous studies showing that these neurons are responsive to NGF, support the concept that NGF acts as trophic factor for magnocellular cholinergic neurons.