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ENeuro 2021The regulation of neuronal soma size is essential for appropriate brain circuit function and its dysregulation is associated with several neurodevelopmental disorders. A...
The regulation of neuronal soma size is essential for appropriate brain circuit function and its dysregulation is associated with several neurodevelopmental disorders. A defect in the dendritic growth and elaboration of motor neocortical pyramidal neurons in neonates lacking neuregulin-4 (NRG4) has previously been reported. In this study, we investigated whether the loss of NRG4 causes further morphologic defects that are specific to these neurons. We analyzed the soma size of pyramidal neurons of layer (L)2/3 and L5 of the motor cortex and a subpopulation of multipolar interneurons in this neocortical region in and mice. There were significant decreases in pyramidal neuron soma size in mice compared with littermates at all stages studied [postnatal day (P)10, P30, and P60]. The reduction was especially marked at P10 and in L5 pyramidal neurons. Soma size was not significantly different for multipolar interneurons at any age. This phenotype was replicated in pyramidal neurons cultured from mice and was rescued by NRG treatment. Analysis of a public single-cell RNA sequencing repository revealed discrete and expression in subpopulations of L5 pyramidal neurons, suggesting that the observed defects were due in part to loss of autocrine Nrg4/ErbB4 signaling. The pyramidal phenotype in the motor cortex of mice was associated with a lack of Rotarod test improvement in P60 mice, suggesting that absence of NRG4 causes alterations in motor performance.
Topics: Animals; Mice; Mice, Knockout; Motor Cortex; Neuregulins; Neurons; Pyramidal Cells
PubMed: 33495243
DOI: 10.1523/ENEURO.0288-20.2021 -
Journal of Anatomy Oct 2015The medial nucleus of the amygdala (Me) is a component of the neural circuit for the interpretation of multimodal sensory stimuli and the elaboration of emotions and...
The medial nucleus of the amygdala (Me) is a component of the neural circuit for the interpretation of multimodal sensory stimuli and the elaboration of emotions and social behaviors in primates. We studied the presence, distribution, diverse shape, and connectivity of dendritic spines in the human Me of adult postmortem men. Data were obtained from the five types of multipolar neurons found in the Me using an adapted Golgi method and light microscopy, the carbocyanine DiI fluorescent dye and confocal microscopy, and transmission electron microscopy. Three-dimensional reconstruction of spines showed a continuum of shapes and sizes, with the spines either lying isolated or forming clusters. These dendritic spines were classified as stubby/wide, thin, mushroom-like, ramified or with an atypical morphology including intermediate shapes, double spines, and thorny excrescences. Pleomorphic spines were found from proximal to distal dendritic branches suggesting potential differences for synaptic processing, strength, and plasticity in the Me neurons. Furthermore, the human Me has large and thin spines with a gemmule appearance, spinules, and filopodium. The ultrastructural data showed dendritic spines forming monosynaptic or multisynaptic contacts at the spine head and neck, and with asymmetric or symmetric characteristics. Additional findings included en passant, reciprocal, and serial synapses in the Me. Complex long-necked thin spines were observed in this subcortical area. These new data reveal the diversity of the dendritic spines in the human Me likely involved with the integration and processing of local synaptic inputs and with functional implications in physiological and various neuropathological conditions.
Topics: Aged; Amygdala; Axons; Cadaver; Dendrites; Dendritic Spines; Humans; Male; Microscopy, Confocal; Microscopy, Electron, Transmission; Middle Aged
PubMed: 26218827
DOI: 10.1111/joa.12358 -
Journal of Anatomy Oct 2021Adult neurons of several reptiles still retain the ability of axonal regeneration in contrast to the low intrinsic regenerative capacity of those in the central nervous...
Adult neurons of several reptiles still retain the ability of axonal regeneration in contrast to the low intrinsic regenerative capacity of those in the central nervous system (CNS) in mammals. This feature of the reptilian neurons has provided a perfect model for elucidating the regenerative mechanism lost in the mammalian counterparts. However, little information is available on the primary culture method of adult reptilian neurons, which greatly limits their valuable applications. In the present study, we introduced a simple and easy method for the isolation, culture, and identification of neurons from the cerebral cortex using the adult geckos. The cultured cells were further identified by immunofluorescence using antibodies against neuron-specific markers β-Ⅲ-tubulin and NeuN. The cortical neurons from adult gecko displayed spindle-shaped, bipolar, or multipolar morphology with a plump soma. This primary culture method for adult reptilian neurons will be beneficial for comparative studies of neuronal biology in various vertebrates.
Topics: Animals; Cerebral Cortex; Lizards; Mammals; Neurons
PubMed: 34047374
DOI: 10.1111/joa.13461 -
Journal of Neurotrauma Oct 2012In order to quantify degenerative and regenerative changes and analyze the contribution of multiple factors to the outcome after neurite transection, we cultured adult...
In order to quantify degenerative and regenerative changes and analyze the contribution of multiple factors to the outcome after neurite transection, we cultured adult mouse dorsal root ganglion neurons, and with a precise laser beam, we transected the nerve fibers they extended. Cell preparations were continuously visualized for 24 h with time-lapse microscopy. More distal cuts caused a more elongated field of degeneration, while thicker neurites degenerated faster than thinner ones. Transected neurites degenerated more if the uncut neurites of the same neuron simultaneously degenerated. If any of these uncut processes regenerated, the transected neurites underwent less degeneration. Regeneration of neurites was limited to distal cuts. Unipolar neurons had shorter regeneration than multipolar ones. Branching slowed the regenerative process, while simultaneous degeneration of uncut neurites increased it. Proximal lesions, small neuronal size, and extensive and rapid neurite degeneration were predictive of death of an injured neuron, which typically displayed necrotic rather than apoptotic form. In conclusion, this in vitro model proved useful in unmasking many new aspects and correlates of mechanically-induced neurite injury.
Topics: Animals; Axotomy; Female; Ganglia, Spinal; Lasers; Male; Mice; Mice, Inbred BALB C; Microdissection; Nerve Regeneration; Neurites
PubMed: 20121423
DOI: 10.1089/neu.2009.0947 -
Anatomical Record (Hoboken, N.J. : 2007) Sep 2021The anterior ventral nucleus neurons in of the camel brain were morphologically studied by Golgi impregnation method. Two neuronal types of were found in the camel...
The anterior ventral nucleus neurons in of the camel brain were morphologically studied by Golgi impregnation method. Two neuronal types of were found in the camel anterior ventral thalamic nucleus, namely, Golgi-type I neurons and Golgi-type II neurons. Those neurons were generally similar to their counterparts in the human thalamus. The Golgi-type I neurons exhibited medium to large cell body (mean diameter = 25 μm) which was either multipolar or triangular in shape. They had from 3 to 10 primary dendrites with many branches but with no spines or appendages. The Golgi-type II neurons had small to medium size (somatic mean diameter = 17.5 μm), their cell bodies were variable in shape, some were round, and others were multipolar or fusiform. These cells bodies had two to six primary dendrites with few branches that may have spines and/or grape-like appendages. Our findings shed some light on the anterior ventral thalamic nucleus structure of the camel as one of the strongest adaptive mammals to the hard climatic conditions.
Topics: Animals; Camelus; Dendrites; Neurons; Thalamic Nuclei; Ventral Thalamic Nuclei
PubMed: 33554482
DOI: 10.1002/ar.24592 -
Journal of Anatomy Sep 2019In the adult human brain, the interstitial neurons (WMIN) of the subcortical white matter are the surviving remnants of the fetal subplate zone. It has been suggested...
In the adult human brain, the interstitial neurons (WMIN) of the subcortical white matter are the surviving remnants of the fetal subplate zone. It has been suggested that they perform certain important functions and may be involved in the pathogenesis of several neurological and psychiatric disorders. However, many important features of this class of human cortical neurons remain insufficiently explored. In this study, we analyzed the total number, and regional and topological distribution of WMIN in the adult human subcortical white matter, using a combined immunocytochemical (NeuN) and stereological approaches. We found that the average number of WMIN in 1 mm of the subcortical white matter is 1.230 ± 549, which translates to the average total number of 593 811 183.6 ± 264 849 443.35 of WMIN in the entire subcortical telencephalic white matter. While there were no significant differences in their regional distribution, the lowest number of WMIN has been consistently observed in the limbic cortex, and the highest number in the frontal cortex. With respect to their topological distribution, the WMIN were consistently more numerous within gyral crowns, less numerous along gyral walls and least numerous at the bottom of cortical sulci (where they occupy a narrow and compact zone below the cortical-white matter border). The topological location of WMIN is also significantly correlated with their morphology: pyramidal and multipolar forms are the most numerous within gyral crowns, whereas bipolar forms predominate at the bottom of cortical sulci. Our results indicate that WMIN represent substantial neuronal population in the adult human cerebral cortex (e.g. more numerous than thalamic or basal ganglia neurons) and thus deserve more detailed morphological and functional investigations in the future.
Topics: Humans; Neurons; White Matter
PubMed: 31173356
DOI: 10.1111/joa.13018 -
The Journal of Neuroscience : the... Oct 1984Neurons in the monkey and rat cerebral cortex immunoreactive for somatostatin tetradecapeptide (SRIF) and for neuropeptide Y (NPY) were examined in the light and...
Neurons in the monkey and rat cerebral cortex immunoreactive for somatostatin tetradecapeptide (SRIF) and for neuropeptide Y (NPY) were examined in the light and electron microscope. Neurons immunoreactive for either peptide are found in all areas of monkey cortex examined as well as throughout the rat cerebral cortex and in the subcortical white matter of both species. In monkey and rat cortex, SRIF-positive neurons are morphologically very similar to NPY-positive neurons. Of the total population of SRIF-positive and NPY-positive neurons in sensory-motor and parietal cortex of monkeys, a minimum of 24% was immunoreactive for both peptides. Most cell bodies are small (8 to 10 micron in diameter) and are present through the depth of the cortex but are densest in layers II-III, in layer VI, and in the subjacent white matter. From the cell bodies several processes commonly emerge, branch two or three times, become beaded, and extend for long distances through the cortex. The fields formed by these processes vary from cell to cell; therefore, the usual morphological terms bipolar, multipolar, and so on do not adequately characterize the full population of neurons. Virtually every cell, however, has at least one long vertically oriented process, and most processes of white matter cells ascent into the cortex. No processes could be positively identified with the light microscope as axons. The processes of the peptide-positive neurons form dense plexuses in the cortex. In each area of monkey cortex, SRIF-positive and NPY-positive processes form a superficial plexus in layers I and II and a deep plexus in layer VI. These plexuses vary in density from area to area. All appear to arise from cortical or white matter cells rather than from extrinsic afferents. In some areas such as SI and areas 5 and 7, the superficial plexus extends deeply into layers III and IV; and in area 17, two very prominent middle plexuses occur in layers IIIB through IVB and in the upper one-third of layer V; these are separated by layer IVC, a major zone of thalamic terminations, which contains very few SRIF- or NPY-positive processes. The density of the plexuses is greater for NPY-positive processes than for SRIF-positive processes in all areas. In the rat, the plexuses do not display a strict laminar organization but generally are densest in the supragranular layers (I to III) and decline steadily in the deeper layers.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Animals; Cerebral Cortex; Female; Histocytochemistry; Immunochemistry; Macaca fascicularis; Male; Nerve Endings; Nerve Tissue Proteins; Neurons; Neuropeptide Y; Rats; Rats, Inbred Strains; Somatostatin; Synapses; Tissue Distribution
PubMed: 6149273
DOI: 10.1523/JNEUROSCI.04-10-02497.1984 -
Proceedings of the National Academy of... Sep 2020The establishment of axon/dendrite polarity is fundamental for neurons to integrate into functional circuits, and this process is critically dependent on microtubules...
The establishment of axon/dendrite polarity is fundamental for neurons to integrate into functional circuits, and this process is critically dependent on microtubules (MTs). In the early stages of the establishment process, MTs in axons change dramatically with the morphological building of neurons; however, how the MT network changes are triggered is unclear. Here we show that CAMSAP1 plays a decisive role in the neuronal axon identification process by regulating the number of MTs. Neurons lacking CAMSAP1 form a multiple axon phenotype in vitro, while the multipolar-bipolar transition and radial migration are blocked in vivo. We demonstrate that the polarity regulator MARK2 kinase phosphorylates CAMSAP1 and affects its ability to bind to MTs, which in turn changes the protection of MT minus-ends and also triggers asymmetric distribution of MTs. Our results indicate that the polarized MT network in neurons is a decisive factor in establishing axon/dendritic polarity and is initially triggered by polarized signals.
Topics: Animals; Cell Polarity; Gene Expression Regulation; Immunoprecipitation; Mice; Microtubule-Associated Proteins; Microtubules; Neurons; Paclitaxel; Protein Binding
PubMed: 32839317
DOI: 10.1073/pnas.1913177117 -
ELife May 2022Migration of cells in the developing brain is integral for the establishment of neural circuits and function of the central nervous system. While migration modes during...
Migration of cells in the developing brain is integral for the establishment of neural circuits and function of the central nervous system. While migration modes during which neurons employ predetermined directional guidance of either preexisting neuronal processes or underlying cells have been well explored, less is known about how cells featuring multipolar morphology migrate in the dense environment of the developing brain. To address this, we here investigated multipolar migration of horizontal cells in the zebrafish retina. We found that these cells feature several hallmarks of amoeboid-like migration that enable them to tailor their movements to the spatial constraints of the crowded retina. These hallmarks include cell and nuclear shape changes, as well as persistent rearward polarization of stable F-actin. Interference with the organization of the developing retina by changing nuclear properties or overall tissue architecture hampers efficient horizontal cell migration and layer formation showing that cell-tissue interplay is crucial for this process. In view of the high proportion of multipolar migration phenomena observed in brain development, the here uncovered amoeboid-like migration mode might be conserved in other areas of the developing nervous system.
Topics: Amoeba; Animals; Cell Movement; Neurons; Retina; Zebrafish
PubMed: 35639083
DOI: 10.7554/eLife.76408 -
PLoS Computational Biology May 2023Peripheral nerve stimulation is being investigated as a therapeutic tool in several clinical scenarios. However, the adopted devices have restricted ability to obtain...
Peripheral nerve stimulation is being investigated as a therapeutic tool in several clinical scenarios. However, the adopted devices have restricted ability to obtain desired outcomes with tolerable off-target effects. Recent promising solutions are not yet employed in clinical practice due to complex required surgeries, lack of long-term stability, and implant invasiveness. Here, we aimed to design a neural interface to address these issues, specifically dimensioned for pudendal and sacral nerves to potentially target sexual, bladder, or bowel dysfunctions. We designed the adaptable intrafascicular radial electrode (AIR) through realistic computational models. They account for detailed human anatomy, inhomogeneous anisotropic conductance, following the trajectories of axons along curving and branching fascicles, and detailed biophysics of axons. The model was validated against available experimental data. Thanks to computationally efficient geometry-based selectivity estimations we informed the electrode design, optimizing its dimensions to obtain the highest selectivity while maintaining low invasiveness. We then compared the AIR with state-of-the-art electrodes, namely InterStim leads, multipolar cuffs and transversal intrafascicular multichannel electrodes (TIME). AIR, comprising a flexible substrate, surface active sites, and radially inserted intrafascicular needles, is designed to be implanted in a few standard steps, potentially enabling fast implants. It holds potential for repeatable stimulation outcomes thanks to its radial structural symmetry. When compared in-silico, AIR consistently outperformed cuff electrodes and InterStim leads in terms of recruitment threshold and stimulation selectivity. AIR performed similarly or better than a TIME, with quantified less invasiveness. Finally, we showed how AIR can adapt to different nerve sizes and varying shapes while maintaining high selectivity. The AIR electrode shows the potential to fill a clinical need for an effective peripheral nerve interface. Its high predicted performance in all the identified requirements was enabled by a model-based approach, readily applicable for the optimization of electrode parameters in any peripheral nerve stimulation scenario.
Topics: Humans; Equipment Design; Electric Stimulation; Electrodes; Peripheral Nerves; Axons; Electrodes, Implanted
PubMed: 37228174
DOI: 10.1371/journal.pcbi.1011184