scholarly journals Cerebellar Culture Models of Dendritic Spine Proliferation After Transplantation of Glia

1997 ◽  
Vol 6 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Fredrick J. Seil
Keyword(s):  
Purkinje Cell ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Cortical Neurons ◽  
Synapse Formation ◽  
Granule Cells ◽  
Axon Terminals ◽  
Neuronal Membranes ◽  
Culture Models

Studies of Purkinje cell dendritic spine proliferation after transplantation of cytosine arabinoside (Ara C) treated organotypic cerebellar cultures with glia and granule cells, either separately and in combination, were reviewed. Exposure of cerebellar explants to Ara C for the first 5 days in vitro results in the destruction of granule cells, the only excitatory cortical neurons, and oligodendroglia, and functionally compromises surviving astrocytes so that they do not appose neuronal membranes. In the absence of granule cells, there is a sprouting of Purkinje cell recurrent axon collaterals, the terminals of which project to and form heterotypical synapses with Purkinje cell dendritic spines, which are usually occupied by terminals of granule cell axons (parallel fibers). After this reorganization has been achieved, the explants can be transplanted with the missing elements to induce a second round of reorganization, with approximate restoration of the usual interneuronal relationships. Addition of both granule cells and glia resulted in a proliferation of clusters of Purkinje cell dendritic spines, which formed synapses with axon terminals of transplanted granule cells, and as synapse formation progressed, the spine clusters became reduced. Transplantation of Ara C-treated cultures with glia alone resulted in a proliferation of clusters of Purkinje cell dendritic spines, but in the absence of granule cells the spines remained unattached, and the clusters persisted throughout the period of observation. Purkinje cell dendritic spine proliferation was induced by exposure of Ara C-treated cultures to astrocyte-conditioned medium. When Ara C-treated cerebella cultures were transplanted with granule cells in the absence of functional glia, parallel fiber- Purkinje cell dendritic spine synapses formed, but no clusters of Purkinje cell dendritic spines were observed. These findings suggest that Purkinje cell dendritic spine proliferation is induced by an astrocyte-secreted factor, resulting in an expansion of postsynaptic sites available for synaptogenesis.

scholarly journals Pannexin 1 regulates spiny protrusion dynamics in cortical neurons

2020 ◽  
Author(s):  
Juan C. Sanchez-Arias ◽  
Rebecca C. Candlish ◽  
Leigh Anne Swayne
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Cortical Neurons ◽  
Neuronal Networks ◽  
Local Environment ◽  
Spine Density ◽  
Pannexin 1 ◽  
Developing Neurons ◽  
The Impact

AbstractThe integration of neurons into networks relies on the formation of dendritic spines. These specialized structures arise from dynamic filopodia-like spiny protrusions. Recently, it was discovered that cortical neurons lacking the channel protein Pannexin 1 (Panx1) exhibited larger and more complicated neuronal networks, as well as, higher dendritic spine densities. Here, we expanded on those findings to investigate whether the increase in dendritic spine density associated with lack of Panx1 was due to differences in the rates of spine dynamics. Using a fluorescent membrane tag (mCherry-CD9-10) to visualize spiny protrusions in developing neurons (at 10 days-in-vitro, DIV10) we confirmed that lack of Panx1 leads to higher spiny protrusion density while transient transfection of Panx1 leads to decreased spiny protrusion density. To quantify the impact of Panx1 expression on spiny protrusion formation, elimination, and motility, we used live cell imaging in DIV10 neurons (1 frame every 5 seconds for 10 minutes). We discovered, that at DIV10, lack of Panx1 KO stabilized spiny protrusions. Notably, re-expression of Panx1 in Panx1 knockout neurons resulted in a significant increase in spiny protrusion motility and turnover. In summary, these new data revealed that Panx1 regulates the development of dendritic spines by controlling protrusion dynamics.Significance statementCells in the brain form intricate and specialized networks - neuronal networks - in charge of processing sensations, executing movement commands, and storing memories. To do this, brain cells extend microscopic protrusions - spiny protrusions - which are highly dynamic and survey the local environment to contact other cells. Those contact sites are known as synapses and undergo further stabilization and maturation establishing the function and efficiency of neuronal networks. Our work shows that removal of Panx1 increases the stability and decreases the turnover of spiny protrusion on young neurons.

scholarly journals Bergmann glial ensheathment of dendritic spines regulates synapse number without affecting spine motility

2010 ◽  
Vol 6 (3) ◽  
pp. 193-200 ◽  
Author(s):  
Jocelyn J. Lippman Bell ◽  
Tamar Lordkipanidze ◽  
Natalie Cobb ◽  
Anna Dunaevsky
Keyword(s):  
Purkinje Cell ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Adenoviral Vector ◽  
Spine Density ◽  
Dendritic Spine Density ◽  
Spine Dynamics

In the cerebellum, lamellar Bergmann glial (BG) appendages wrap tightly around almost every Purkinje cell dendritic spine. The function of this glial ensheathment of spines is not entirely understood. The development of ensheathment begins near the onset of synaptogenesis, when motility of both BG processes and dendritic spines are high. By the end of the synaptogenic period, ensheathment is complete and motility of the BG processes decreases, correlating with the decreased motility of dendritic spines. We therefore have hypothesized that ensheathment is intimately involved in capping synaptogenesis, possibly by stabilizing synapses. To test this hypothesis, we misexpressed GluR2 in an adenoviral vector in BG towards the end of the synaptogenic period, rendering the BG α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) Ca2+-impermeable and causing glial sheath retraction. We then measured the resulting spine motility, spine density and synapse number. Although we found that decreasing ensheathment at this time does not alter spine motility, we did find a significant increase in both synaptic pucta and dendritic spine density. These results indicate that consistent spine coverage by BG in the cerebellum is not necessary for stabilization of spine dynamics, but is very important in the regulation of synapse number.

scholarly journals EPAC2 is required for corticotropin-releasing hormone-mediated spine loss

2019 ◽  
Author(s):  
Zhong Xie ◽  
Peter Penzes ◽  
Deepak P. Srivastava
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Cortical Neurons ◽  
Acute Stress ◽  
Critical Role ◽  
Small Gtpase ◽  
Corticotropin Releasing Hormone ◽  
Rapid Loss ◽  
Primary Cortical Neurons ◽  
Releasing Hormone

AbstractCorticotropin-releasing hormone (CRH) is produced in response to stress. This hormone plays a key role in mediating neuroendocrine, behavioral, and autonomic responses to stress. The CRH receptor 1 (CRHR1) is expressed in multiple brain regions including the cortex and hippocampus. Previous studies have shown that activation of CRHR1 by CRH results in the rapid loss of dendritic spines. Exchange protein directly activated by cAMP (EPAC2, also known as RapGEF4), a guanine nucleotide exchange factor (GEF) for the small GTPase Rap, has been linked with CRHR1 signaling. EPAC2 plays a critical role in regulating dendritic spine morphology and number in response to several extracellular signals. But whether EPAC2 links CRHR1 with dendritic spine remodeling is unknown. Here we show that CRHR1 is highly enriched in the dendritic spines of primary cortical neurons. Furthermore, we find that EPAC2 and CRHR1 co-localize in cortical neurons. Critically, short hairpin RNA-mediated knockdown of Epac2 abolished CRH-mediated spine loss in primary cortical neurons. Taken together, our data indicate that EPAC2 is required for the rapid loss of dendritic spines induced by CRH. These findings identify a novel pathway by which acute exposure to CRH may regulate synaptic structure and ultimately responses to acute stress.

scholarly journals Neurotrophic Effect of Fish-Lecithin Based Nanoliposomes on Cortical Neurons

Marine Drugs ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. 406 ◽  
Author(s):  
Catherine Malaplate ◽  
Aurelia Poerio ◽  
Marion Huguet ◽  
Claire Soligot ◽  
Elodie Passeri ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cortical Neurons ◽  
Neuronal Development ◽  
Synapse Formation ◽  
Fatty Acid Content ◽  
Primary Cultures ◽  
Synaptic Membrane ◽  
Neuronal Membranes ◽  
Acid Ratio ◽  
And Function

Lipids play multiple roles in preserving neuronal function and synaptic plasticity, and polyunsaturated fatty acids (PUFAs) have been of particular interest in optimizing synaptic membrane organization and function. We developed a green-based methodology to prepare nanoliposomes (NL) from lecithin that was extracted from fish head by-products. These NL range between 100–120 nm in diameter, with an n-3/n-6 fatty acid ratio of 8.88. The high content of n-3 PUFA (46.3% of total fatty acid content) and docosahexanoic acid (26%) in these NL represented a means for enrichment of neuronal membranes that are potentially beneficial for neuronal growth and synaptogenesis. To test this, the primary cultures of rat embryo cortical neurons were incubated with NL on day 3 post-culture for 24 h, followed by immunoblots or immunofluorescence to evaluate the NL effects on synaptogenesis, axonal growth, and dendrite formation. The results revealed that NL-treated cells displayed a level of neurite outgrowth and arborization on day 4 that was similar to those of untreated cells on day 5 and 6, suggesting accelerated synapse formation and neuronal development in the presence of NL. We propose that fish-derived NL, by virtue of their n-3 PUFA profile and neurotrophic effects, represent a new innovative bioactive vector for developing preventive or curative treatments for neurodegenerative diseases.

Toward a Brain-Inspired Developmental Neural Network Based on Dendritic Spine Dynamics

2021 ◽  
pp. 1-18
Author(s):  
Feifei Zhao ◽  
Yi Zeng ◽  
Jun Bai
Keyword(s):  
Neural Network ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Synapse Formation ◽  
Dynamic Structure ◽  
Classification Performance ◽  
Synaptic Activity ◽  
Data Sets ◽  
Spine Density ◽  
Spine Dynamics

Abstract Neural networks with a large number of parameters are prone to overfitting problems when trained on a relatively small training set. Introducing weight penalties of regularization is a promising technique for solving this problem. Taking inspiration from the dynamic plasticity of dendritic spines, which plays an important role in the maintenance of memory, this letter proposes a brain-inspired developmental neural network based on dendritic spine dynamics (BDNN-dsd). The dynamic structure changes of dendritic spines include appearing, enlarging, shrinking, and disappearing. Such spine plasticity depends on synaptic activity and can be modulated by experiences—in particular, long-lasting synaptic enhancement/suppression (LTP/LTD), coupled with synapse formation (or enlargement)/elimination (or shrinkage), respectively. Subsequently, spine density characterizes an approximate estimate of the total number of synapses between neurons. Motivated by this, we constrain the weight to a tunable bound that can be adaptively modulated based on synaptic activity. Dynamic weight bound could limit the relatively redundant synapses and facilitate the contributing synapses. Extensive experiments demonstrate the effectiveness of our method on classification tasks of different complexity with the MNIST, Fashion MNIST, and CIFAR-10 data sets. Furthermore, compared to dropout and L2 regularization algorithms, our method can improve the network convergence rate and classification performance even for a compact network.

scholarly journals CEREBELLAR ALTERATIONS IN THE WEAVER MOUSE

1973 ◽  
Vol 56 (2) ◽  
pp. 478-486 ◽  
Author(s):  
Asao Hirano ◽  
Herbert M. Dembitzer
Keyword(s):  
Fine Structure ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Dendritic Spines ◽  
Granule Cells ◽  
Parallel Fibers ◽  
Mechanisms Of Development ◽  
Weaver Mouse

The fine structure of the cerebellum of weaver mouse was examined and the paucity of granule cells and their axons, the parallel fibers, was confirmed. Unexpectedly, however, the dendritic spines of the Purkinje cells which, in normal animals, are the postsynaptic mates of the parallel fibers, were present. Furthermore, their essential morphology and their staining reactions were indistinguishable from those of the Purkinje cell dendritic spines in normal animals. Possible mechanisms of development are discussed.

scholarly journals ROCK1 and 2 differentially regulate actomyosin organization to drive cell and synaptic polarity

2015 ◽  
Vol 210 (2) ◽  
pp. 225-242 ◽  
Author(s):  
Karen A. Newell-Litwa ◽  
Mathilde Badoual ◽  
Hannelore Asmussen ◽  
Heather Patel ◽  
Leanna Whitmore ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Actin Polymerization ◽  
Synapse Formation ◽  
Leading Edge ◽  
Actin Remodeling ◽  
Rac1 Activity ◽  
Dendritic Spine Morphology ◽  
Filament Bundles ◽  
Migratory Cells

RhoGTPases organize the actin cytoskeleton to generate diverse polarities, from front–back polarity in migrating cells to dendritic spine morphology in neurons. For example, RhoA through its effector kinase, RhoA kinase (ROCK), activates myosin II to form actomyosin filament bundles and large adhesions that locally inhibit and thereby polarize Rac1-driven actin polymerization to the protrusions of migratory fibroblasts and the head of dendritic spines. We have found that the two ROCK isoforms, ROCK1 and ROCK2, differentially regulate distinct molecular pathways downstream of RhoA, and their coordinated activities drive polarity in both cell migration and synapse formation. In particular, ROCK1 forms the stable actomyosin filament bundles that initiate front–back and dendritic spine polarity. In contrast, ROCK2 regulates contractile force and Rac1 activity at the leading edge of migratory cells and the spine head of neurons; it also specifically regulates cofilin-mediated actin remodeling that underlies the maturation of adhesions and the postsynaptic density of dendritic spines.

scholarly journals Precise levels of nectin-3 are required for proper synapse formation in postnatal visual cortex

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Johanna Tomorsky ◽  
Philip R. L. Parker ◽  
Chris Q. Doe ◽  
Cristopher M. Niell
Keyword(s):  
Visual Cortex ◽  
Dendritic Spine ◽  
Cortical Neurons ◽  
Synapse Formation ◽  
Ocular Dominance ◽  
Developmental Time ◽  
Basal Dendrites ◽  
Layer 2 ◽  
Eye Opening ◽  
Visual Cortical

Abstract Background Developing cortical neurons express a tightly choreographed sequence of cytoskeletal and transmembrane proteins to form and strengthen specific synaptic connections during circuit formation. Nectin-3 is a cell-adhesion molecule with previously described roles in synapse formation and maintenance. This protein and its binding partner, nectin-1, are selectively expressed in upper-layer neurons of mouse visual cortex, but their role in the development of cortical circuits is unknown. Methods Here we block nectin-3 expression (via shRNA) or overexpress nectin-3 in developing layer 2/3 visual cortical neurons using in utero electroporation. We then assay dendritic spine densities at three developmental time points: eye opening (postnatal day (P)14), one week following eye opening after a period of heightened synaptogenesis (P21), and at the close of the critical period for ocular dominance plasticity (P35). Results Knockdown of nectin-3 beginning at E15.5 or ~ P19 increased dendritic spine densities at P21 or P35, respectively. Conversely, overexpressing full length nectin-3 at E15.5 decreased dendritic spine densities when all ages were considered together. The effects of nectin-3 knockdown and overexpression on dendritic spine densities were most significant on proximal secondary apical dendrites. Interestingly, an even greater decrease in dendritic spine densities, particularly on basal dendrites at P21, was observed when we overexpressed nectin-3 lacking its afadin binding domain. Conclusion These data collectively suggest that the proper levels and functioning of nectin-3 facilitate normal synapse formation after eye opening on apical and basal dendrites in layer 2/3 of visual cortex.

scholarly journals Chronic and Acute Manipulation of Cortical Glutamate Transmission Induces Structural and Synaptic Changes in Co-cultured Striatal Neurons

2021 ◽  
Vol 15 ◽  
Author(s):  
Naila Kuhlmann ◽  
Miriam Wagner Valladolid ◽  
Lucía Quesada-Ramírez ◽  
Matthew J. Farrer ◽  
Austen J. Milnerwood
Keyword(s):  
Nmda Receptor ◽  
Cortical Neurons ◽  
Synapse Formation ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Projection Neurons ◽  
Spine Density ◽  
Striatal Neurons ◽  
Synapse Plasticity

In contrast to the prenatal topographic development of sensory cortices, striatal circuit organization is slow and requires the functional maturation of cortical and thalamic excitatory inputs throughout the first postnatal month. While mechanisms regulating synapse development and plasticity are quite well described at excitatory synapses of glutamatergic neurons in the neocortex, comparatively little is known of how this translates to glutamate synapses onto GABAergic neurons in the striatum. Here we investigate excitatory striatal synapse plasticity in an in vitro system, where glutamate can be studied in isolation from dopamine and other neuromodulators. We examined pre-and post-synaptic structural and functional plasticity in GABAergic striatal spiny projection neurons (SPNs), co-cultured with glutamatergic cortical neurons. After synapse formation, medium-term (24 h) TTX silencing increased the density of filopodia, and modestly decreased dendritic spine density, when assayed at 21 days in vitro (DIV). Spine reductions appeared to require residual spontaneous activation of ionotropic glutamate receptors. Conversely, chronic (14 days) TTX silencing markedly reduced spine density without any observed increase in filopodia density. Time-dependent, biphasic changes to the presynaptic marker Synapsin-1 were also observed, independent of residual spontaneous activity. Acute silencing (3 h) did not affect presynaptic markers or postsynaptic structures. To induce rapid, activity-dependent plasticity in striatal neurons, a chemical NMDA receptor-dependent “long-term potentiation (LTP)” paradigm was employed. Within 30 min, this increased spine and GluA1 cluster densities, and the percentage of spines containing GluA1 clusters, without altering the presynaptic signal. The results demonstrate that the growth and pruning of dendritic protrusions is an active process, requiring glutamate receptor activity in striatal projection neurons. Furthermore, NMDA receptor activation is sufficient to drive glutamatergic structural plasticity in SPNs, in the absence of dopamine or other neuromodulators.

scholarly journals Cytoplasmic organization in cerebellar dendritic spines.

1983 ◽  
Vol 97 (4) ◽  
pp. 1169-1178 ◽  
Author(s):  
D M Landis ◽  
T S Reese
Keyword(s):  
Purkinje Cell ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
The Body ◽  
Rapid Freezing ◽  
Synaptic Junction ◽  
Cytoplasmic Organization ◽  
Synaptic Junctions ◽  
Cerebellar Tissue

Three sets of filamentous structures were found to be associated with synaptic junctions in slices of cerebellar tissue prepared by rapid-freezing and freeze-etch techniques. The electron-dense fuzz subjacent to postsynaptic membranes corresponds to a web of 4-6-nm-diam filaments that were clearly visualized in rapid-frozen, freeze-etched preparations. Purkinje cell dendritic spines are filled with a meshwork of 5-7-nm filaments that were found to contact the spine membrane everywhere except at the synaptic junction, and extend through the neck of the spine into the parent dendrite. In addition, 8-10-nm microfilaments, possibly actin, were seen to be associated with the postsynaptic web and to extend into the body and neck of the spine. The arrangements and attachments of the filamentous elements in the Purkinje cell dendritic spine may account for its shape.

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