Dendritic Trunks Research Articles

Reversal of neuronal and cognitive consequences of amphetamine sensitization following chronic treatment with a D1 antagonist

Neuroplasticity is a key factor in restoration of brain function following neuropathology associated with disease or drug exposure. Here we examined the potential for chronic treatment with the selective D1 receptor antagonist SCH39166 to reverse the profound and enduring cognitive impairment associated with amphetamine (AMPH) sensitization in the nonhuman primate and to stimulate re-growth of atrophied pyramidal dendrites in the dorsolateral prefrontal cortex of these animals. Four rhesus monkeys with sustained cognitive impairment (> 1 year following AMPH sensitization) were treated for up to 8 months with SCH39166. Cognitive testing was performed before, during, and for up to 1½ year following treatment. Significant improvement in working memory performance was observed only after cessation of the D1 antagonist treatment but then was sustained for the duration of the post-treatment testing period. Postmortem quantitative assessment of Golgi-impregnated pyramidal neurons in BA9 showed that apical dendritic length and trunk spine density were increased in D1 antagonist treated monkeys relative to AMPH-sensitized and AMPH-naïve monkeys. These findings, which suggest that the deleterious consequences of AMPH sensitization can be reversed by modulation of D1 receptor signaling, have implications for treating the underlying neural basis of cognitive deficits in both schizophrenia and substance abuse.

Numerical and Experimental Investigation of NH<sub>4</sub>Cl Solidification

This paper deals with the validation of a volume averaged multiphase solidification model based on a benchmark experiment using NH4Cl-H2O as model alloy and Particle Image Velocimetry (PIV) as optical measurement method. For the numerical modelling of the solidification, different phases (e.g. liquid, equiaxed grains and columnar dendrite trunks) have been considered. The mass, momentum, energy conservation and species transport equations for each phase have been solved. The Eulerian-Eulerian model equations have been implemented in the commercial Finite Volume Method based software FLUENT-ANSYS v6.3 using User-Defined Functions (UDF). The mass transfer has been modelled by diffusion controlled crystal growth. The simulation of the NH4Cl-H2O solidification has been numerically investigated as a two-dimensional unsteady process in the cross-section of a 100 x 80 x 10 (mm3) experimental benchmark. Since during the experiment both columnar and equiaxed growth of NH4Cl have been observed, both phenomena have been considered in the simulation. The predicted distribution of the solidification front and the measured thickness of the mushy zone have been compared with the measurements.

Columnar to Equiaxed Transition During Ingot Casting Using Ternary Alloy Composition

The present paper deals with the formation of macrosegregation in a benchmark ingot using (Fe-C-Cr) ternary alloy composition. The numerical investigation of complex multiphase phenomena is a difficult study, because the thermophysical properties depend strongly on the temperature, concentration, pressure and chemical composition as well. For the numerical modeling of solidification and melting processes different phases (e.g. liquid, equiaxed crystals and columnar dendrite trunks) have been considered. The mass, momentum, energy conservation and species conservation equations for each phase have been solved. The Eulerian-Eulerian model equations have been implemented in the commercial Finite Volume Method based FLUENT-ANSYS v6.3 CFD software using User-Defined Functions (UDF). The mass transfer has been modelled by diffusion controlled crystal growth by applying an advanced tip tracking algorithm for columnar solidification. The modeling of the grain density transport has been improved. The derivatives of the mass fraction quantities for each component appear in the nucleation rate term. It means that we obtain a new term of the right hand side of the grain density transport equation for using ternary alloy composition. This paper focuses on both the process and simulation parameters and their influence on the macrosegregation formation. The results show that the macrosegregation pattern does not change significantly above a well-chosen number of grid cells, and the computational time could be decreased, when the time step size has been increased.

The immediate large-scale dendritic plasticity of cortical pyramidal neurons subjected to acute epidural compression

Head trauma and acute disorders often instantly compress the cerebral cortex and lead to functional abnormalities. Here we used rat epidural bead implantation model and investigated the immediate changes following acute compression. The dendritic arbors of affected cortical pyramidal neurons were filled with intracellular dye and reconstructed 3-dimensionally for analysis. Compression was found to shorten the apical, but not basal, dendrites of underlying layer III and V cortical pyramidal neurons and reduced dendritic spines on the entire dendritic arbor immediately. Dendrogram analysis showed that in addition to distal, proximal apical dendrites also quickly reconfigured. We then focused on apical dendritic trunks and explored how proximal dendrites were rapidly altered. Compression instantly twisted the microtubules and deformed the membrane contour of dendritic trunks likely a result of the elastic nature of dendrites as immediate decompression restored it and stabilization of microtubules failed to block it. Subsequent adaptive remodeling restored plasmalemma and microtubules to normal appearance in 3 days likely via active mechanisms as taxol blocked the restoration of microtubules and in addition partly affected plasmalemmal reorganization which presumably engaged recycling of excess membrane. In short, the structural dynamics and the associated mechanisms that we revealed demonstrate how compression quickly altered the morphology of cortical output neurons and hence cortical functions consequently.

T-SNARE and v-SNARE in the GABAergic and glutamatergic synapses of the rat cerebellar cortex

Using light microscope immunohistochemistry, the distributions of the t-SNARE, SNAP-25 and syntaxin-1a, and v-SNARE, VAMP-2 (or synaptobrevin-2), have been analyzed in the rat cerebellar cortex and compared with those of GAD-65/67, marker of GABAergic neurons, and vGLUT-1 and vGLUT-2, markers of glutamatergic neurons. SNAP-25 immunoreactivity was detected throughout the cortex, highly diffused in the neuropil. In the molecular and Purkinje layers, the immunoreactivity surrounded dendrite trunks of the Purkinje neurons, and bodies of stellate, basket and Purkinje neurons, which appeared all immunonegative. In the granular layer, the immunoreactivity was less diffuse and formed small grains localized within the protoplasmic islands of Held (synaptic glomeruli). Immunoreactivity was also observed in the white matter. The distribution of syntaxin-1a immunoreactivity appeared superimposable to that of SNAP-25. VAMP-2 immunoreactivity was observed in small dots finely dispersed in the neuropil of the molecular/Purkinje layer; a moderate labelling of the Purkinje neuron bodies was also observed. In the granular layer, VAMP-2 immunoreactivity formed larger deposits, presumably corresponding to mossy fibre terminals. Experiments of double labelling immunohistochemistry revealed no co-localization between t-SNARE (SNAP-25) or v-SNARE (VAMP-2) and GAD-65/67. On the contrary, co-localization between SNAP-25 and VAMP-2, on one side, and v-GLUT-1 or vGLUT-2, on the other side, was frequently revealed. Briefly, in the molecular layer, v-GLUT-1 and vGLUT-2-positive terminals only partly displayed also SNAP-25 immunoreactivity; whereas in the granular layer, all v-GLUT-1 and vGLUT-2-positive terminals displayed this co-localization. The results of this study indicate that t-SNARE and v-SNARE largely characterize the glutamatergic synapses in the rat cerebellar cortex. The same proteins are lacking in the GABAergic synapses.

Mesoscopic Simulation of Dendritic Growth Observed in X-ray Video Microscopy During Directional Solidification of Al–Cu Alloys

A mesoscopic model is developed to simulate microstructures observed in situ by X-ray video microscopy during directional solidification of Al–Cu alloys in a Hele–Shaw cell. In the model, a volume-averaged species conservation equation is solved to obtain the solute concentration and solid fraction fields, and an analytical stagnant film model is used to predict the motion of the dendrite envelopes. The model is carefully validated in several test cases. Then, the model is applied to simulate the columnar dendritic microstructures observed in the X-ray video microscopy experiments for two different alloy compositions. Reasonable agreement is found between the measured and predicted dendrite envelope shapes, solid fractions, and solute concentration fields. The predicted size of the mushy zone and the extent of the undercooled melt region ahead of the columnar front agree well with the in situ experimental observations. The simulation results show quantitative agreement with the internal solid fraction variations measured from the radiographs. The present model is also able to realistically simulate a primary dendrite trunk spacing adjustment that was observed in one of the experiments. Overall, the present study represents the first successful validation of a solidification model using real time, in situ data from an experiment with a metallic alloy. Considerable additional research is needed to account in the model for the effect of gravity driven melt convection.

Rho kinase inhibition protects CA1 cells in organotypic hippocampal slices during in vitro ischemia

The actin cytoskeleton is a dynamic superstructure that regulates multiple cellular functions and that has been implicated in cell death regulation. We investigated whether modulating the neuronal actin cytoskeleton polymerization by Rho-GTPase kinase (ROCK) inhibition influences cell death in hippocampal neuronal cultures and in murine organotypic hippocampal slice cultures subjected to in vitro ischemia (IVI). During IVI, spines on vehicle treated hippocampal neurons collapsed and large dendritic actin aggregates were formed. Following ROCK inhibition by Y27632, the actin aggregates were markedly smaller while large filopodia extended from the dendritic trunk. Y27632 also provided strong neuroprotection of hippocampal pyramidal CA1 neurons, which was of similar magnitude as protection by NMDA receptor blockade. Likewise, treatment with the F-actin depolymerizing agent latrunculin during IVI diminished actin aggregation and mitigated cell death following IVI. We propose that ROCK inhibition protects neurons against ischemic damage by disrupting actin polymerization thereby mitigating NMDA receptor induced toxicity and releasing ATP bound to actin for cellular energy use. We conclude that ROCK inhibitors abrogate multiple detrimental processes and could therefore be useful in stroke therapy.

An arithmetic rule for spatial summation of excitatory and inhibitory inputs in pyramidal neurons

Dendritic integration of excitatory and inhibitory inputs is critical for neuronal computation, but the underlying rules remain to be elucidated. Based on realistic modeling and experiments in rat hippocampal slices, we derived a simple arithmetic rule for spatial summation of concurrent excitatory glutamatergic inputs (E) and inhibitory GABAergic inputs (I). The somatic response can be well approximated as the sum of the excitatory postsynaptic potential (EPSP), the inhibitory postsynaptic potential (IPSP), and a nonlinear term proportional to their product (k*EPSP*IPSP), where the coefficient k reflects the strength of shunting effect. The k value shows a pronounced asymmetry in its dependence on E and I locations. For I on the dendritic trunk, k decays rapidly with E-I distance for proximal Es, but remains largely constant for distal Es, indicating a uniformly high shunting efficacy for all distal Es. For I on an oblique branch, the shunting effect is restricted mainly within the branch, with the same proximal/distal asymmetry. This asymmetry can be largely attributed to cable properties of the dendrite. Further modeling studies showed that this rule also applies to the integration of multiple coincident Es and Is. Thus, this arithmetic rule offers a simple analytical tool for studying E-I integration in pyramidal neurons that incorporates the location specificity of GABAergic shunting inhibition.

Experimental and numerical investigations of NH4Cl solidification in a mould Part 2: numerical results

This paper deals with the validation of a multiphase solidification model based on a benchmark experiment presented in Part 1. For the numerical modelling of NH4Cl–H2O solidification, the three different phases liquid, columnar dendrite trunks and equiaxed grains have been considered. The mass, momentum, energy conservation and species transport equations for each phase have been solved. The multiphase Eulerian-Eulerian model equations have been implemented in the Finite Volume Method based commercial software FLUENT-ANSYS using User-Defined Functions (UDF). The simulation of the NH4Cl–H2O solidification has been numerically investigated as a twodimensional unsteady process representing a cross-section of a 100 × 80 × 10 mm experimental benchmark. During the experiment both columnar and equiaxed growth of NH4Cl were observed, therefore both phenomena were considered in the simulation. The predicted distribution of the solidification front has been compared with the measurements.

Stochastic modeling of columnar dendritic grain growth in weld pool of Al‐Cu alloy

AbstractA multi‐scale model is used to simulate columnar dendritic growth in TIG (tungsten inert‐gas) weld molten pool of Al‐Cu alloy. The grain morphologies at the edge of the weld pool are studied. The simulated results indicate that the average primary dendrite spacing changes during the solidification process in the weld pool because of the complicated thermal field, solute diffusion field and competitive growth. And it is shown that the secondary dendrite arms grow insufficiently in the space between dendrite trunks if the primary dendrite spacing is small. And the phenomenon has been explained by analyzing the influence of the solute accumulation on the constitutional undercooling and undercooling gradient when there are two different opposite solute diffusion fields. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

Synaptic removal of diacylglycerol by DGKζ and PSD-95 regulates dendritic spine maintenance

Diacylglycerol (DAG) is an important lipid signalling molecule that exerts an effect on various effector proteins including protein kinase C. A main mechanism for DAG removal is to convert it to phosphatidic acid (PA) by DAG kinases (DGKs). However, it is not well understood how DGKs are targeted to specific subcellular sites and tightly regulates DAG levels. The neuronal synapse is a prominent site of DAG production. Here, we show that DGKzeta is targeted to excitatory synapses through its direct interaction with the postsynaptic PDZ scaffold PSD-95. Overexpression of DGKzeta in cultured neurons increases the number of dendritic spines, which receive the majority of excitatory synaptic inputs, in a manner requiring its catalytic activity and PSD-95 binding. Conversely, DGKzeta knockdown reduces spine density. Mice deficient in DGKzeta expression show reduced spine density and excitatory synaptic transmission. Time-lapse imaging indicates that DGKzeta is required for spine maintenance but not formation. We propose that PSD-95 targets DGKzeta to synaptic DAG-producing receptors to tightly couple synaptic DAG production to its conversion to PA for the maintenance of spine density.

Solute distribution in KNbO3 melt-solution and its effect on dendrite growth during rapid solidification

This paper reports that the rapid solidification of mixed Li2B4O7 and KNbO3 melted in a Pt loop heater has been performed experimentally by the method of quenching, and various morphologies of KNbO3 crystals have been observed in different regions of the quenched melt-solution. Dendrites were formed in the central region where mass transfer is performed by diffusion, whereas polygonal crystals with smooth surface grew in the marginal region where convection dominates mass transport. Based on measurement of KNbO3 concentration along crystal interface by electronic probe analysis, it finds the variety of crystal morphologies, which is the result of different solute distributions: in the central region the inhomogeneity of solute concentration is much sharper and morphological instability is easier to take place; nevertheless in the marginal region the concentration homogeneity has been greatly enhanced by convection which prevents the occurrence of morphological instability. Additional solute distribution in the melt along the primary dendrite trunk axis as well as that in mushy zones has also been determined. Results show that the solute concentration in the liquid increases linearly with distance from the trunk tip and more solutes were found to be concentrated in mushy zones. The closer the mushy zone is to trunk tip, the lower the solute concentration will be there.

Analysis of Solidified Structure Constituted with Dendrites by Using Solid Analytical Geometry

Solidified structure near the chill zone is complex, since the growth directions of dendrites are not in accordance with the observed plane. Many lines, which are called ghost lines, can be observed in the solidified structure. The ghost lines have been analyzed applying the solid analytical geometry. Dendrite of cubic metals has been simplified with rod as a dendrite trunk and four plates with the same thickness. In order to characterize the solidified pattern, angles of ghost lines (η and ξ) are chosen and calculated using θ, φ and β, which are the important parameters to indicate the dendrite orientation in the space. The calculated results have been confirmed by the experimental results solidified unidirectionally of Al–20mass%Cu alloy. It has been found that the spacing or thickness of ghost lines may be the useful parameters to characterize the spatial array of dendrites with respect to the plane for observation.

EBSD: a powerful microstructure analysis technique in the field of solidification

This paper presents a few examples of the application of electron back-scatter diffraction (EBSD) to solidification problems. For directionally solidified Al-Zn samples, this technique could reveal the change in dendrite growth directions from <100> to <110> as the composition of zinc increases from 5 to 90 wt%. The corresponding texture evolution and grain selection mechanisms were also examined. Twinned dendrites that form under certain solidification conditions in Al-X specimens (with X = Zn, Mg, Ni, Cu) were clearly identified as <110> dendrite trunks split in their centre by a (111) twin plane. In Zn-0.2 wt% Al hot-dip galvanized coatings on steel sheets, EBSD clearly revealed the preferential basal orientation distribution of the nuclei as well as the reinforcement of this distribution by the faster growth of <1010> dendrites. Moreover, in Al-Zn-Si coatings, misorientations as large as 10 degrees mm(-1) have been measured within individual grains. Finally, the complex band and lamellae microstructures that form in the Cu-Sn peritectic system at low growth rate could be shown to constitute a continuous network initiated from a single nucleus. EBSD also showed that the alpha and beta phases had a Kurdjumov-Sachs crystallographic relationship.

Immunohistochemistry of GluR1 subunits of AMPA receptors of rat cerebellar nerve cells

The localization of GluR1 subunits of ionotropic glutamate receptors in the glial cells and inhibitory neurons of cerebellar cortex and their association with the climbing and parallel fibers, and basket cell axons were studied. Samples of P14 and P21 rat cerebellar cortex were exposed to a specific antibody against GluR1 subunit(s) ofAMPA receptors and were examined with confocal laser scanning microscopy. GluR1 strong immunoreactivity was confined to Purkinje cell and the molecular layer. Weak GluR1 immunoreactivity was observed surrounding some Golgi cells in the granule cell layer. Intense GluR1 immunoreactivity was localized around Purkinje, basket, and stellate cells. Purkinje cells expressed strong GluR1 immunoreactivity surrounding the cell body, primary dendritic trunk and secondary and tertiary spiny dendritic branches. Marked immunofluorescent staining was also detected in the Bergmann glial fibers at the level of middle and outer third molecular layer. Positive immunofluorescence staining was also observed surrounding basket and stellate cells, and in the capillary wall. These findings suggest the specific localization of GluR1 subunits ofAMPA receptors in Bergmann glial cells, inhibitory cerebellar neurons, and the associated excitatory glutamatergic circuits formed by climbing and parallel fibers, and by the inhibitory basket cell axons.

The cytoarchitecture and soma-dendritic arbors of the pyramidal neurons of aged rat sensorimotor cortex: An intracellular dye injection study

We studied the cytoarchitecture and dendritic arbors of the output neurons of the sensorimotor cortex of aged rats and found that although individual cortical layer became thinner, the overall cytoarchitecture and neuron densities remained comparable to those of young adults. To find out whether aging affects cortical outputs we studied the soma-dendritic arbors of layers III and V pyramidal neurons, main output neurons of the cerebral cortex, using brain slice intracellular dye injection technique. With a fluorescence microscope, selected neurons were filled with fluorescence dye under visual guidance. Injected slices were resectioned into thinner sections for converting the injected dye into non-fading material immunohistochemically. The long apical dendritic trunk and branches could be routinely revealed. This allowed us to reconstruct and study the dendritic arbors of these neurons in isolation in 300-μm-thick dimension. Analysis shows that their cell bodies did not shrink, but the densities of spines on dendrites and the total dendritic length significantly reduced. Among spines, those with long thin stalks thought to be involved in memory acquisition appeared to be reduced. These could underlie the compromise of sensorimotor functions following aging.

Activity and localization of the Secretory Pathway Ca 2+-ATPase isoform 1 (SPCA1) in different areas of the mouse brain during postnatal development

Ca 2+ and Mn 2+ play an important role in many events in the nervous system, ranging from neural morphogenesis to neurodegeneration. As part of the homeostatic control of these ions, the Secretory Pathway Ca 2+-ATPase isoform 1 (SPCA1) mediates the accumulation of Ca 2+ or Mn 2+ with high affinity into Golgi reservoirs. This SPCA1 represents a relatively recently characterized P-type pump that is highly expressed in nervous tissue, but information on its involvement in neural maturation is currently lacking. In this study, we have analyzed the expression and distribution of the SPCA1 pump in mouse brain during postnatal development. RT-PCR and Western blot assays showed that SPCA1 is particularly highly expressed at nearly constant levels during this entire period of development in cortex, hippocampus, and cerebellum. In spite of the apparently unchanged expression levels, functional assays showed that SPCA-associated Ca 2+-ATPase activity increased with the stage of development in these areas. Immunohistochemical studies pointed to SPCA1 localization in Golgi stacks of the soma and the initial part of primary dendritic trunk in main cortical, hippocampal and cerebellar neurons from the earliest postnatal stages. This suggests a potential role in intracellular signaling and in Golgi secretory processes involved in dendritic growth and in functional maturation of the mouse nervous system.

The Back and Forth of Dendritic Plasticity

Synapses are located throughout the often-elaborate dendritic tree of central neurons. Hebbian models of plasticity require temporal association between synaptic input and neuronal output to produce long-term potentiation of excitatory transmission. Recent studies have highlighted how active dendritic spiking mechanisms control this association. Here, we review new work showing that associative synaptic plasticity can be generated without neuronal output and that the interplay between neuronal architecture and the active electrical properties of the dendritic tree regulates synaptic plasticity.

Dendritic crystallization in thin films of PEO/PMMA blends: A comparison to crystallization in small molecule liquids

Dendritic crystallization of poly(ethylene oxide) (PEO)/poly(methyl methacrylate) (PMMA) thin films is reported. The film thickness is kept constant while the PMMA molar mass and blend composition are varied. Some basic features of dendritic growth, such as the diffusion length and tip curvature are discussed. The diffusion coefficient is tuned by varying the molar mass of the non-crystallizable PMMA and the blend composition. The observed dendrite tip radius is on the order of 50nm and the shape of the growth envelope varies from square to needle-like as the PMMA molar mass or PMMA content is increased. The sidebranch spacing increases with the distance from the dendrite trunk with a power-law relationship that is also dependent on the PMMA molar mass and PMMA content. This coarsening process is similar to that reported for other classes of materials. These similarities (the curved dendrite tip, power-law relationship of the sidebranches, and the sidebranch coarsening processes) indicate that the large scale crystallization morphologies of the polymeric materials we study are similar to those found in crystallization of small molecules and metals.

Dendrite-to-Soma Input/Output Function of Continuous Time-Varying Signals in Hippocampal CA1 Pyramidal Neurons

We examined how hippocamal CA1 neurons process complex time-varying inputs that dendrites are likely to receive in vivo. We propose a functional model of the dendrite-to-soma input/output relationship that combines temporal integration and static-gain control mechanisms. Using simultaneous dual whole cell recordings, we injected 50 s of subthreshold and suprathreshold zero-mean white-noise current into the primary dendritic trunk along the proximal 2/3 of stratum radiatum and measured the membrane potential at the soma. Applying a nonlinear system-identification analysis, we found that a cascade of a linear filter followed by an adapting static-gain term fully accounted for the nonspiking input/output relationship between the dendrite and soma. The estimated filters contained a prominent band-pass region in the 1- to 10-Hz frequency range that remained constant as a function of stimulus variance. The gain of the dendrite-to-soma input/output relationship, in contrast, varied as a function of stimulus variance. When the contribution of the voltage-dependent current I(h) was eliminated, the estimated filters lost their band-pass properties and the gain regulation was substantially altered. Our findings suggest that the dendrite-to-soma input/output relationship for proximal apical inputs to CA1 pyramidal neurons is well described as a band-pass filter in the theta frequency range followed by a gain-control nonlinearity that dynamically adapts to the statistics of the input signal.