neuronal morphology
Recently Published Documents


TOTAL DOCUMENTS

657
(FIVE YEARS 235)

H-INDEX

59
(FIVE YEARS 8)

2021 ◽  
Vol 17 (12) ◽  
pp. e1009754
Author(s):  
Elishai Ezra-Tsur ◽  
Oren Amsalem ◽  
Lea Ankri ◽  
Pritish Patil ◽  
Idan Segev ◽  
...  

Retinal direction-selectivity originates in starburst amacrine cells (SACs), which display a centrifugal preference, responding with greater depolarization to a stimulus expanding from soma to dendrites than to a collapsing stimulus. Various mechanisms were hypothesized to underlie SAC centrifugal preference, but dissociating them is experimentally challenging and the mechanisms remain debatable. To address this issue, we developed the Retinal Stimulation Modeling Environment (RSME), a multifaceted data-driven retinal model that encompasses detailed neuronal morphology and biophysical properties, retina-tailored connectivity scheme and visual input. Using a genetic algorithm, we demonstrated that spatiotemporally diverse excitatory inputs–sustained in the proximal and transient in the distal processes–are sufficient to generate experimentally validated centrifugal preference in a single SAC. Reversing these input kinetics did not produce any centrifugal-preferring SAC. We then explored the contribution of SAC-SAC inhibitory connections in establishing the centrifugal preference. SAC inhibitory network enhanced the centrifugal preference, but failed to generate it in its absence. Embedding a direction selective ganglion cell (DSGC) in a SAC network showed that the known SAC-DSGC asymmetric connectivity by itself produces direction selectivity. Still, this selectivity is sharpened in a centrifugal-preferring SAC network. Finally, we use RSME to demonstrate the contribution of SAC-SAC inhibitory connections in mediating direction selectivity and recapitulate recent experimental findings. Thus, using RSME, we obtained a mechanistic understanding of SACs’ centrifugal preference and its contribution to direction selectivity.


2021 ◽  
Vol 23 (1) ◽  
pp. 290
Author(s):  
Erin Clabough ◽  
James Ingersoll ◽  
Tyler Reekes ◽  
Alyssa Gleichsner ◽  
Amy Ryan

Fetal alcohol spectrum disorders are caused by the disruption of normal brain development in utero. The severity and range of symptoms is dictated by both the dosage and timing of ethanol administration, and the resulting developmental processes that are impacted. In order to investigate the effects of an acute, high-dose intoxication event on the development of medium spiny neurons (MSNs) in the striatum, mice were injected with ethanol on P6, and neuronal morphology was assessed after 24 h, or at 1 month or 5 months of age. Data indicate an immediate increase in MSN dendritic length and branching, a rapid decrease in spine number, and increased levels of the synaptic protein PSD-95 as a consequence of this neonatal exposure to ethanol, but these differences do not persist into adulthood. These results demonstrate a rapid neuronal response to ethanol exposure and characterize the dynamic nature of neuronal architecture in the MSNs. Although differences in neuronal branching and spine density induced by ethanol resolve with time, early changes in the caudate/putamen region have a potential impact on the execution of complex motor skills, as well as aspects of long-term learning and addictive behavior.


2021 ◽  
Author(s):  
Muneesh Pal ◽  
Divya Chaubey ◽  
Mohit Tanwar ◽  
Beena Pillai

Abstract The Kalrn gene encodes several multi-domain protein isoforms that localise to neuronal synapses, and play dynamic roles in shaping axonal outgrowth, dendrite morphology and dendritic spine re-modelling. The genomic locus is implicated in several neurodevelopmental and neuropsychiatric diseases including autism, schizophrenia and bipolar disease. Mutations in the coding regions, inherited in a classical Mendelian manner, have also been implicated in certain forms of autism and intellectual disability. At the molecular level, the protein isoforms, encoded by reported transcript isoforms, share some core domains arising from the central exons, while other domains, especially towards the C terminal may be selectively incorporated. This heterogeneity seems to confer the ability to grow and retract dendritic spines, thus making Kalirin a critical and dynamic player in dendritogenesis. We have previously shown that in the zebrafish genome, a novel brain specific non-coding RNA arising from the 5’ end of the Kalirin gene, durga regulates neuronal morphology. In search of the mammalian equivalent, we characterized the mammalian Kalrn loci in detail, annotating multiple novel non-coding RNAs, including linear and circular variants, through analysis of transcriptomics data and experimental approaches. By comparing the mouse and human loci and studying the expression of the novel lncRNAs arising from the locus during differentiation of primary cortical neurons in culture, we show that certain non-coding RNAs arising from the locus show a temporal expression profile that coincides with a subset of Kalirin protein coding isoforms. In humans, mouse and zebrafish the 5’end of the Kalrn locus gives rise to a chromatin associated lncRNA that is present in adult ovaries besides being expressed during brain development and in certain regions of the adult brain. Besides correcting some of the annotations available in public databases, we propose that this lncRNA arising from the 5’end of the Kalrn locus is the mammalian ortholog of zebrafish lncRNA durga.


2021 ◽  
Vol 13 ◽  
Author(s):  
Afzal Misrani ◽  
Sidra Tabassum ◽  
Qingwei Huo ◽  
Sumaiya Tabassum ◽  
Jinxiang Jiang ◽  
...  

Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide. Mitochondrial dysfunction is thought to be an early event in the onset and progression of AD; however, the precise underlying mechanisms remain unclear. In this study, we investigated mitochondrial proteins involved in organelle dynamics, morphology and energy production in the medial prefrontal cortex (mPFC) and hippocampus (HIPP) of young (1∼2 months), adult (4∼5 months) and aged (9∼10, 12∼18 months) APP/PS1 mice. We observed increased levels of mitochondrial fission protein, Drp1, and decreased levels of ATP synthase subunit, ATP5A, leading to abnormal mitochondrial morphology, increased oxidative stress, glial activation, apoptosis, and altered neuronal morphology as early as 4∼5 months of age in APP/PS1 mice. Electrophysiological recordings revealed abnormal miniature excitatory postsynaptic current in the mPFC together with a minor connectivity change between the mPFC and HIPP, correlating with social deficits. These results suggest that abnormal mitochondrial dynamics, which worsen with disease progression, could be a biomarker of early-stage AD. Therapeutic interventions that improve mitochondrial function thus represent a promising approach for slowing the progression or delaying the onset of AD.


2021 ◽  
Author(s):  
Karl Marrett ◽  
Muye Zhu ◽  
Yuze Chi ◽  
Zhe Chen ◽  
Chris Choi ◽  
...  

Interpreting the influx of microscopy and neuroimaging data is bottlenecked by neuronal reconstruction's long-standing issues in accuracy, automation, and scalability. Rapidly increasing data size is particularly concerning for modern computing infrastructure due to the wall in memory bandwidth which historically has witnessed the slowest rate of technological advancement. Recut is an end to end reconstruction pipeline that takes raw large-volume light microscopy images and yields filtered or tuned automated neuronal reconstructions that require minimal proofreading and no other manual intervention. By leveraging adaptive grids and other methods, Recut also has a unified data representation with up to a 509× reduction in memory footprint resulting in an 89.5× throughput increase and enabling an effective 64× increase in the scale of volumes that can be skeletonized on servers or resource limited devices. Recut also employs coarse and fine-grained parallelism to achieve speedup factors beyond CPU core count in sparse settings when compared to the current fastest reconstruction method. By leveraging the sparsity in light microscopy datasets, this can allow full brains to be processed in-memory, a property which may significantly shift the compute needs of the neuroimaging community. The scale and speed of Recut fundamentally changes the reconstruction process, allowing an interactive yet deeply automated workflow.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260005
Author(s):  
Monica C. Lannom ◽  
Joshua Nielsen ◽  
Aatiqa Nawaz ◽  
Temirlan Shilikbay ◽  
Stephanie Ceman

Fragile X syndrome results from the loss of expression of the Fragile X Mental Retardation Protein (FMRP). FMRP and RNA helicase Moloney Leukemia virus 10 (MOV10) are important Argonaute (AGO) cofactors for miRNA-mediated translation regulation. We previously showed that MOV10 functionally associates with FMRP. Here we quantify the effect of reduced MOV10 and FMRP expression on dendritic morphology. Murine neurons with reduced MOV10 and FMRP phenocopied Dicer1 KO neurons which exhibit impaired dendritic maturation Hong J (2013), leading us to hypothesize that MOV10 and FMRP regulate DICER expression. In cells and tissues expressing reduced MOV10 or no FMRP, DICER expression was significantly reduced. Moreover, the Dicer1 mRNA is a Cross-Linking Immunoprecipitation (CLIP) target of FMRP Darnell JC (2011), MOV10 Skariah G (2017) and AGO2 Kenny PJ (2020). MOV10 and FMRP modulate expression of DICER1 mRNA through its 3’untranslated region (UTR) and introduction of a DICER1 transgene restores normal neurite outgrowth in the Mov10 KO neuroblastoma Neuro2A cell line and branching in MOV10 heterozygote neurons. Moreover, we observe a global reduction in AGO2-associated microRNAs isolated from Fmr1 KO brain. We conclude that the MOV10-FMRP-AGO2 complex regulates DICER expression, revealing a novel mechanism for regulation of miRNA production required for normal neuronal morphology.


2021 ◽  
Vol 13 ◽  
Author(s):  
Le Xu ◽  
Yiying Zhou ◽  
Linbo Hu ◽  
Hongde Jiang ◽  
Yibei Dong ◽  
...  

The N-methyl-D-aspartate receptor is a critical molecule for synaptic plasticity and cognitive function. Impaired synaptic plasticity is thought to contribute to the cognitive impairment associated with Alzheimer’s disease (AD). However, the neuropathophysiological alterations of N-methyl-D-aspartate receptor (NMDAR) function and synaptic plasticity in hippocampal CA1 in transgenic rodent models of AD are still unclear. In the present study, APP/PS1 mice were utilized as a transgenic model of AD, which exhibited progressive cognitive impairment including defective working memory, recognition memory, and spatial memory starting at 6 months of age and more severe by 8 months of age. We found an impaired long-term potentiation (LTP) and reduced NMDAR-mediated spontaneous excitatory postsynaptic currents (sEPSCs) in the hippocampal CA1 of APP/PS1 mice with 8 months of age. Golgi staining revealed that dendrites of pyramidal neurons had shorter length, fewer intersections, and lower spine density in APP/PS1 mice compared to control mice. Further, the reduced expression levels of NMDAR subunits, PSD95 and SNAP25 were observed in the hippocampus of APP/PS1 mice. These results suggest that NMDAR dysfunction, impaired synaptic plasticity, and disrupted neuronal morphology constitute an important part of the neuropathophysiological alterations associated with cognitive impairment in APP/PS1 mice.


2021 ◽  
Author(s):  
Maria Belen Harreguy ◽  
Esha Shah ◽  
Zainab Tanvir ◽  
Blandine Simprevil ◽  
Tracy S. Tran ◽  
...  

Extracellular signaling proteins serve as neuronal growth cone guidance molecules during development and are well positioned to be involved in neuronal regeneration and recovery from injury. Semaphorins and their receptors, the plexins, are a family of conserved proteins involved in development that, in the nervous system, are axonal guidance cues mediating axon pathfinding and synapse formation. The Caenorhabditis elegans genome encodes for three semaphorins and two plexin receptors: the transmembrane semaphorins, SMP-1 and SMP-2, signal through their receptor, PLX-1, while the secreted semaphorin, MAB-20, signals through PLX-2. Here, we determined the neuronal morphology and locomotion behavior of knockout animals missing each of the semaphorins and plexins; we described the expression pattern of all plexins in the nervous system of C. elegans; and we evaluated their effect on the regeneration of motoneuron neurites and the recovery of locomotion behavior following precise laser microsurgery.


Genetics ◽  
2021 ◽  
Author(s):  
J Christopher Rounds ◽  
Edwin B Corgiat ◽  
Changtian Ye ◽  
Joseph A Behnke ◽  
Seth M Kelly ◽  
...  

Abstract Nab2 encodes the Drosophila melanogaster member of a conserved family of zinc finger polyadenosine RNA-binding proteins (RBPs) linked to multiple steps in post-transcriptional regulation. Mutation of the Nab2 human ortholog ZC3H14 gives rise to an autosomal recessive intellectual disability but understanding of Nab2/ZC3H14 function in metazoan nervous systems is limited, in part because no comprehensive identification of metazoan Nab2/ZC3H14-associated RNA transcripts has yet been conducted. Moreover, many Nab2/ZC3H14 functional protein partnerships remain unidentified. Here, we present evidence that Nab2 genetically interacts with Ataxin-2 (Atx2), which encodes a neuronal translational regulator, and that these factors coordinately regulate neuronal morphology, circadian behavior, and adult viability. We then present the first high-throughput identifications of Nab2- and Atx2-associated RNAs in Drosophila brain neurons using RNA immunoprecipitation-sequencing (RIP-Seq). Critically, the RNA interactomes of each RBP overlap, and Nab2 exhibits high specificity in its RNA associations in neurons in vivo, associating with a small fraction of all polyadenylated RNAs. The identities of shared associated transcripts (e.g., drk, me31B, stai) and of transcripts specific to Nab2 or Atx2 (e.g., Arpc2 and tea) promise insight into neuronal functions of, and genetic interactions between, each RBP. Consistent with prior biochemical studies, Nab2-associated neuronal RNAs are overrepresented for internal A-rich motifs, suggesting these sequences may partially mediate Nab2 target selection. These data support a model where Nab2 functionally opposes Atx2 in neurons, demonstrate Nab2 shares associated neuronal RNAs with Atx2, and reveal Drosophila Nab2 associates with a more specific subset of polyadenylated mRNAs than its polyadenosine affinity alone may suggest.


2021 ◽  
Vol 14 ◽  
Author(s):  
Akiko Tabuchi ◽  
Daisuke Ihara

Accumulating evidence suggests that the serum response factor (SRF) cofactor megakaryoblastic leukemia (MKL)/myocardin-related transcription factor (MRTF) has critical roles in many physiological and pathological processes in various cell types. MKL/MRTF molecules comprise MKL1/MRTFA and MKL2/MRTFB, which possess actin-binding motifs at the N-terminus, and SRF-binding domains and a transcriptional activation domain (TAD) at the C-terminus. Several studies have reported that, in association with actin rearrangement, MKL/MRTF translocates from the cytoplasm to the nucleus, where it regulates SRF-mediated gene expression and controls cell motility. Therefore, it is important to elucidate the roles of MKL/MRTF in the nervous system with regard to its structural and functional regulation by extracellular stimuli. We demonstrated that MKL/MRTF is highly expressed in the brain, especially the synapses, and is involved in dendritic complexity and dendritic spine maturation. In addition to the positive regulation of dendritic complexity, we identified several MKL/MRTF isoforms that negatively regulate dendritic complexity in cortical neurons. We found that the MKL/MRTF isoforms were expressed differentially during brain development and the impacts of these isoforms on the immediate early genes including Arc/Arg3.1, were different. Here, we review the roles of MKL/MRTF in the nervous system, with a special focus on the MKL/MRTF-mediated fine-tuning of neuronal morphology and gene transcription. In the concluding remarks, we briefly discuss the future perspectives and the possible involvement of MKL/MRTF in neurological disorders such as schizophrenia and autism spectrum disorder.


Sign in / Sign up

Export Citation Format

Share Document