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Frontiers in Cellular Neuroscience 2022Electrical activity is considered a key driver for the neurochemical and morphological maturation of neurons and the formation of neuronal networks. Designer receptors...
Electrical activity is considered a key driver for the neurochemical and morphological maturation of neurons and the formation of neuronal networks. Designer receptors exclusively activated by designer drugs (DREADDs) are tools for controlling neuronal activity at the single cell level by triggering specific G protein signaling. Our objective was to investigate if prolonged silencing of differentiating cortical neurons can influence dendritic and axonal maturation. The DREADD hM4Di couples to G signaling and evokes hyperpolarization GIRK channels. HM4Di was biolistically transfected into neurons in organotypic slice cultures of rat visual cortex, and activated by clozapine-N-oxide (CNO) dissolved in HO; controls expressed hM4Di, but were mock-stimulated with HO. Neurons were analyzed after treatment for two postnatal time periods, DIV 5-10 and 10-20. We found that CNO treatment delays the maturation of apical dendrites of L2/3 pyramidal cells. Further, the number of collaterals arising from the main axon was significantly lower, as was the number of bouton terminaux along pyramidal cell and basket cell axons. The dendritic maturation of L5/6 pyramidal cells and of multipolar interneurons (basket cells and bitufted cells) was not altered by CNO treatment. Returning CNO-treated cultures to CNO-free medium for 7 days was sufficient to recover dendritic and axonal complexity. Our findings add to the view that activity is a key driver in particular of postnatal L2/3 pyramidal cell maturation. Our results further suggest that inhibitory G protein signaling may represent a factor balancing the strong driving force of neurotrophic factors, electrical activity and calcium signaling.
PubMed: 35910251
DOI: 10.3389/fncel.2022.941620 -
Turkish Neurosurgery 2020To investigate the neuroprotective effect of a N-methyl-D-aspartate (NMDA) receptor antagonist (amantadine) in an experimental spinal cord injury (SCI) model.
AIM
To investigate the neuroprotective effect of a N-methyl-D-aspartate (NMDA) receptor antagonist (amantadine) in an experimental spinal cord injury (SCI) model.
MATERIAL AND METHODS
Thirty male Spragueâ€"Dawley rats were divided into three groups: control (I), SCI (II), and SCI + amantadine (III). SCI was created using clip compression technique. At the end of day 7, blood samples were obtained from the rats and analyzed using various biochemical markers. Histological examination was also performed. MDA, GSH, and MPO assays were done. VEGF, TNF-α, and Baxexpressions were also analyzed.
RESULTS
The group III had several inflammatory cells in the gray and white matter, with mildly degenerated multipolar and bipolar cells. Some bipolar and multipolar neurons showed TNF-α expression; however, TNF-α was found to be weak in small groups of inflammatory cells around the blood vessels in the substantia grisea and alba. Positive Bax expression was observed in the substantia grisea layer, particularly in the membrane of some bipolar neurons and glial cells; however, negative Bax expression was observed in neuron and glial cells and showed positive VEGF expression in the vascular endothelium in the group III.
CONCLUSION
NMDA receptor antagonists, especially amantadine, may ameliorate SCI by inducing angiogenesis, affecting inflammation and apoptosis. It inhibits oxidative stress and the signaling pathways following SCI in rats.
Topics: Amantadine; Animals; Apoptosis; Inflammation; Male; Neurons; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Spinal Cord; Spinal Cord Injuries
PubMed: 32091112
DOI: 10.5137/1019-5149.JTN.26801-19.3 -
Annals of Neurology Mar 2012The cellular basis of cognitive abnormalities in preterm infants with periventricular leukomalacia (PVL) is uncertain. One important possibility is that damage to white... (Comparative Study)
Comparative Study
OBJECTIVE
The cellular basis of cognitive abnormalities in preterm infants with periventricular leukomalacia (PVL) is uncertain. One important possibility is that damage to white matter and subplate neurons that are critical to the formation of the cerebral cortex occurs in conjunction with oligodendrocyte and axonal injury in PVL. We tested the hypothesis that the overall density of neurons in the white matter and subplate region is significantly lower in PVL cases compared to non-PVL controls.
METHODS
We used a computer-based method for the determination of the density of microtubule-associated protein 2-immunolabeled neurons in the ventricular/subventricular region, periventricular white matter, central white matter, and subplate region in PVL cases and controls.
RESULTS
There were 5 subtypes of subcortical neurons: granular, unipolar, bipolar, inverted pyramidal, and multipolar. The neuronal density of the granular neurons in each of the 4 regions was 54 to 80% lower (p≤0.01) in the PVL cases (n=15) compared to controls adjusted for age and postmortem interval (n=10). The overall densities of unipolar, bipolar, multipolar, and inverted pyramidal neurons did not differ significantly between the PVL cases and controls. No granular neurons expressed markers of neuronal and glial immaturity (Tuj1, doublecortin, or NG2).
INTERPRETATION
These data suggest that quantitative deficits in susceptible granular neurons occur in the white matter distant from periventricular foci, including the subplate region, in PVL, and may contribute to abnormal cortical formation and cognitive dysfunction in preterm survivors.
Topics: Cell Count; Cerebral Cortex; Female; Humans; Infant, Newborn; Leukomalacia, Periventricular; Male; Nerve Fibers, Myelinated; Neurons
PubMed: 22451205
DOI: 10.1002/ana.22612 -
RNA Biology Jul 2017The precise spatial and temporal regulation of gene expression orchestrates the many intricate processes during brain development. In the present study we examined the...
The precise spatial and temporal regulation of gene expression orchestrates the many intricate processes during brain development. In the present study we examined the role of the brain-enriched microRNA-338 (miR-338) during mouse cortical development. Reduction of miR-338 levels in the developing mouse cortex, using a sequence-specific miR-sponge, resulted in a loss of neuronal polarity in the cortical plate and significantly reduced the number of neurons within this cortical layer. Conversely, miR-338 overexpression in developing mouse cortex increased the number of neurons, which exhibited a multipolar morphology. All together, our results raise the possibility for a direct role for this non-coding RNA, which was recently associated with schizophrenia, in the regulation of cortical neuronal polarity and layer placement.
Topics: Animals; Base Sequence; Cell Polarity; Cell Shape; Cerebral Cortex; Mice, Inbred C57BL; MicroRNAs; Neurons; Rats, Wistar
PubMed: 28494198
DOI: 10.1080/15476286.2017.1325067 -
Communications Biology Apr 2022Structural synaptic plasticity may underlie experience and learning-dependent changes in cortical circuits. In contrast to excitatory pyramidal neurons, insight into the...
Structural synaptic plasticity may underlie experience and learning-dependent changes in cortical circuits. In contrast to excitatory pyramidal neurons, insight into the structural plasticity of inhibitory neurons remains limited. Interneurons are divided into various subclasses, each with specialized functions in cortical circuits. Further knowledge of subclass-specific structural plasticity of interneurons is crucial to gaining a complete mechanistic understanding of their contribution to cortical plasticity overall. Here, we describe a subpopulation of superficial cortical multipolar interneurons expressing vasoactive intestinal peptide (VIP) with high spine densities on their dendrites located in layer (L) 1, and with the electrophysiological characteristics of bursting cells. Using longitudinal imaging in vivo, we found that the majority of the spines are highly dynamic, displaying lifetimes considerably shorter than that of spines on pyramidal neurons. Using correlative light and electron microscopy, we confirmed that these VIP spines are sites of excitatory synaptic contacts, and are morphologically distinct from other spines in L1.
Topics: Interneurons; Neuronal Plasticity; Neurons; Pyramidal Cells; Vasoactive Intestinal Peptide
PubMed: 35418660
DOI: 10.1038/s42003-022-03278-z -
Cell Reports Jan 2017During brain development, the correct migration of newborn neurons is one of the determinants of circuit formation, and neuronal migration defects may lead to...
During brain development, the correct migration of newborn neurons is one of the determinants of circuit formation, and neuronal migration defects may lead to neurological and psychiatric disorders. The molecular mechanisms underlying neuronal migration and related disorders are poorly understood. Here, we report that Chromodomain Y-like (CDYL) is critical for neuronal migration in mice. Knocking down CDYL caused neuronal migration defects and disrupted both mobility and multipolar-to-bipolar transition of migrating neurons. We find that CDYL regulates neuronal migration by transcriptionally repressing RhoA. In addition, CDYL deficiency increased the excitability of cortical pyramidal neurons and the susceptibility of mice to convulsant-induced seizures. These results demonstrate that CDYL is a regulator of neuronal migration and shed light on the pathogenesis of seizure-related neurodevelopmental disorders.
Topics: Actin Cytoskeleton; Actins; Animals; Brain; Cell Movement; Cell Polarity; Chromatin; Co-Repressor Proteins; Disease Susceptibility; Epilepsy; Gene Knockdown Techniques; Histone Acetyltransferases; Histones; Hydro-Lyases; Male; Mice, Inbred C57BL; Mice, Inbred ICR; Neurons; Pentylenetetrazole; Polymerization; Signal Transduction; rhoA GTP-Binding Protein
PubMed: 28076783
DOI: 10.1016/j.celrep.2016.12.043 -
Frontiers in Systems Neuroscience 2014We studied the topographical distribution and morphological characteristics of NADPH-diaphorase-positive neurons and fibers in the human claustrum. These neurons were...
We studied the topographical distribution and morphological characteristics of NADPH-diaphorase-positive neurons and fibers in the human claustrum. These neurons were seen to be heterogeneously distributed throughout the claustrum. Taking into account the size and shape of stained perikarya as well as dendritic and axonal characteristics, Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd)-positive neurons were categorized by diameter into three types: large, medium and small. Large neurons ranged from 25 to 35 μm in diameter and typically displayed elliptical or multipolar cell bodies. Medium neurons ranged from 20 to 25 μm in diameter and displayed multipolar, bipolar and irregular cell bodies. Small neurons ranged from 14 to 20 μm in diameter and most often displayed oval or elliptical cell bodies. Based on dendritic characteristics, these neurons were divided into spiny and aspiny subtypes. Our findings reveal two populations of NADPHd-positive neurons in the human claustrum-one comprised of large and medium cells consistent with a projection neuron phenotype, the other represented by small cells resembling the interneuron phenotype as defined by previous Golgi impregnation studies.
PubMed: 24904317
DOI: 10.3389/fnsys.2014.00096 -
The EMBO Journal Jan 2023Cortical neuronal networks control cognitive output, but their composition and modulation remain elusive. Here, we studied the morphological and transcriptional...
Cortical neuronal networks control cognitive output, but their composition and modulation remain elusive. Here, we studied the morphological and transcriptional diversity of cortical cholinergic VIP/ChAT interneurons (VChIs), a sparse population with a largely unknown function. We focused on VChIs from the whole barrel cortex and developed a high-throughput automated reconstruction framework, termed PopRec, to characterize hundreds of VChIs from each mouse in an unbiased manner, while preserving 3D cortical coordinates in multiple cleared mouse brains, accumulating thousands of cells. We identified two fundamentally distinct morphological types of VChIs, bipolar and multipolar that differ in their cortical distribution and general morphological features. Following mild unilateral whisker deprivation on postnatal day seven, we found after three weeks both ipsi- and contralateral dendritic arborization differences and modified cortical depth and distribution patterns in the barrel fields alone. To seek the transcriptomic drivers, we developed NuNeX, a method for isolating nuclei from fixed tissues, to explore sorted VChIs. This highlighted differentially expressed neuronal structural transcripts, altered exitatory innervation pathways and established Elmo1 as a key regulator of morphology following deprivation.
Topics: Mice; Animals; Transcriptome; Parietal Lobe; Interneurons; Choline O-Acetyltransferase; Cholinergic Agents; Sensory Receptor Cells; Adaptor Proteins, Signal Transducing
PubMed: 36377476
DOI: 10.15252/embj.2021110565 -
Frontiers in Neural Circuits 2014Both glycine and GABA mediate inhibitory synaptic transmission in the ventral cochlear nucleus (VCN). In mice, the time course of glycinergic inhibition is slow in bushy...
Both glycine and GABA mediate inhibitory synaptic transmission in the ventral cochlear nucleus (VCN). In mice, the time course of glycinergic inhibition is slow in bushy cells and fast in multipolar (stellate) cells, and is proposed to contribute to the processing of temporal cues in both cell types. Much less is known about GABAergic synaptic transmission in this circuit. Electrical stimulation of the auditory nerve or the tuberculoventral pathway evokes little GABAergic synaptic current in brain slice preparations, and spontaneous GABAergic miniature synaptic currents occur infrequently. To investigate synaptic currents carried by GABA receptors in bushy and multipolar cells, we used transgenic mice in which channelrhodopsin-2 and EYFP is driven by the vesicular GABA transporter (VGAT-ChR2-EYFP) and is expressed in both GABAergic and glycinergic neurons. Light stimulation evoked action potentials in EYFP-expressing presynaptic cells, and evoked inhibitory postsynaptic potentials (IPSPs) in non-expressing bushy and planar multipolar cells. Less than 10% of the IPSP amplitude in bushy cells arose from GABAergic synapses, whereas 40% of the IPSP in multipolar neurons was GABAergic. In voltage clamp, glycinergic IPSCs were significantly slower in bushy neurons than in multipolar neurons, whereas there was little difference in the kinetics of the GABAergic IPSCs between two cell types. During prolonged stimulation, the ratio of steady state vs. peak IPSC amplitude was significantly lower for glycinergic IPSCs. Surprisingly, the reversal potentials of GABAergic IPSCs were negative to those of glycinergic IPSCs in both bushy and multipolar neurons. In the absence of receptor blockers, repetitive light stimulation was only able to effectively evoke IPSCs up to 20 Hz in both bushy and multipolar neurons. We conclude that local GABAergic release within the VCN can differentially influence bushy and multipolar cells.
Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Channelrhodopsins; Cochlear Nucleus; Excitatory Amino Acid Antagonists; GABA Antagonists; Glycine; Glycine Agents; Inhibitory Postsynaptic Potentials; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Net; Neural Inhibition; Pyridazines; Sodium Channel Blockers; Strychnine; Synapses; Synaptic Transmission; Tetrodotoxin; Vesicular Inhibitory Amino Acid Transport Proteins; gamma-Aminobutyric Acid
PubMed: 25104925
DOI: 10.3389/fncir.2014.00084 -
The Anatomical Record. Part A,... Mar 2003The gross, light, and electron microscopic anatomies of the porcine intrinsic cardiac nervous system were investigated in 26 pigs to facilitate functional studies in... (Comparative Study)
Comparative Study
The gross, light, and electron microscopic anatomies of the porcine intrinsic cardiac nervous system were investigated in 26 pigs to facilitate functional studies in this model. Gross anatomy: Numerous ganglia and interconnecting nerves (ganglionated plexuses) were found to be concentrated in epicardial fat in five atrial and six ventricular regions. The five atrial ganglionated plexuses identified were (1) the ventral right atrial, (2) the right vena cava-right atrial, (3) the dorsal atrial, (4) the interatrial septal, and (5) the left superior vena cava-left atrial ones. Six ventricular ganglionated plexuses were identified in close proximity to the (1) roots of the aorta and pulmonary artery (craniomedial), extending along the left main coronary artery to the (2) ventral interventricular and (3) circumflex coronary arteries. (4) A ganglionated plexus was identified around the origin of the dorsal interventricular coronary artery, as well as the (5) right main and (6) right marginal coronary arteries. Isolated neurons were identified scattered throughout the cranial interventricular septum. Microscopic anatomy: Approximately 3,000 neuronal somata were estimated to compose this intrinsic cardiac nervous system. Some ganglia contained more than 100 neurons. Neuronal somata had dimensions of roughly 33.1 (short axis) by 46.3 (long axis) microm. Most were multipolar, a small population of unipolar neurons being identified in atrial and ventricular tissues. At the electron microscopic level, asymmetrical axodendritic synapses with small clear, round vesicles were identified, some containing large dense-cored vesicles. In summary, porcine intrinsic cardiac neurons are concentrated in 11 distinct atrial and ventricular ganglionated plexuses. These extensive plexuses, along with fewer scattered neurons, display varied neuronal morphology and synaptology that represent the anatomical substrate for complex information processing within the intrinsic cardiac component of the porcine cardiac neuronal hierarchy. These anatomical data provide a framework for physiological analyses of the porcine intrinsic cardiac nervous system.
Topics: Animals; Female; Ganglia, Sympathetic; Heart; Heart Atria; Heart Ventricles; Immunohistochemistry; Male; Neurons; Swine; Synapses
PubMed: 12552641
DOI: 10.1002/ar.a.10030