Recent Citations: April 2011
Here are some recent articles citing MBF Bioscience Neurolucida and Stereo Investigator software:
Author: G. T. Banks, M. A. Haas, S. Line, H. L. Shepherd, M. AlQatari, S. Stewart, I. Rishal, A. Philpott, B. Kalmar, A. Kuta, M. Groves, N. Parkinson, A. Acevedo-Arozena, S. Brandner, D. Bannerman, L. Greensmith, M. Hafezparast, M. Koltzenburg, R. Deacon, M. Fainzilber and E. M. C. Fisher
Title:Behavioral and Other Phenotypes in a Cytoplasmic Dynein Light Intermediate Chain 1 Mutant Mouse
Journal: The Journal of NeuroscienceVolume: 31 Issue: 14 Pages: 5483-5494 Date: April 6, 2011
Short Title: Behavioral and Other Phenotypes in a Cytoplasmic Dynein Light Intermediate Chain 1 Mutant Mouse
DOI: 10.1523/jneurosci.5244-10.2011
Abstract: The cytoplasmic dynein complex is fundamentally important to all eukaryotic cells for transporting a variety of essential cargoes along microtubules within the cell. This complex also plays more specialized roles in neurons. The complex consists of 11 types of protein that interact with each other and with external adaptors, regulators and cargoes. Despite the importance of the cytoplasmic dynein complex, we know comparatively little of the roles of each component protein, and in mammals few mutants exist that allow us to explore the effects of defects in dynein-controlled processes in the context of the whole organism. Here we have taken a genotype-driven approach in mouse (Mus musculus) to analyze the role of one subunit, the dynein light intermediate chain 1 (Dync1li1). We find that, surprisingly, an N235Y point mutation in this protein results in altered neuronal development, as shown from in vivo studies in the developing cortex, and analyses of electrophysiological function. Moreover, mutant mice display increased anxiety, thus linking dynein functions to a behavioral phenotype in mammals for the first time. These results demonstrate the important role that dynein-controlled processes play in the correct development and function of the mammalian nervous system.
Author: A. Evstratova, S. Chamberland and L. Topolnik
Title: Cell type-specific and activity-dependent dynamics of action potential-evoked Ca2+ signals in dendrites of hippocampal inhibitory interneurons
Journal: The Journal of PhysiologyVolume: 589 Issue: 8 Pages: 1957-1977 Date: April 15, 2011
Short Title: Cell type-specific and activity-dependent dynamics of action potential-evoked Ca2+ signals in dendrites of hippocampal inhibitory interneurons
DOI: 10.1113/jphysiol.2010.204255
Abstract: Action potentials generated at the level of the cell body can propagate back to neuronal dendrites, where they activate different types of voltage-sensitive calcium channels and produce massive calcium influx. Although these calcium signals may control dendritic integration, their mechanisms, dynamic properties and role in different cell types remain largely unknown. We found that in dendrites of hippocampal interneurons, an inhibitory cell type involved in control of network excitability, specific types of calcium channels are present but are recruited in an activity-dependent manner. Furthermore, their activation produces calcium rises spatially restricted to proximal dendritic sites, where they control the efficacy of transmission at inhibitory synapses. The pathway by which this happens appears to constitute a negative feedback loop – increased firing activity of interneurons potentiates the inhibitory drive that they receive, thus decreasing the activity of interneurons further. This may have a profound effect on the recruitment of interneurons and network activity.In most central neurons, action potentials (APs), generated in the initial axon segment, propagate back into dendrites and trigger considerable Ca2+ entry via activation of voltage-sensitive calcium channels (VSCCs). Despite the similarity in its underlying mechanisms, however, AP-evoked dendritic Ca2+ signalling often demonstrates a cell type-specific profile that is determined by the neuron dendritic properties. Using two-photon Ca2+ imaging in combination with patch-clamp whole-cell recordings, we found that in distinct types of hippocampal inhibitory interneurons Ca2+ transients evoked by backpropagating APs not only were shaped by the interneuron-specific properties of dendritic Ca2+ handling but also involved specific Ca2+ mechanisms that were regulated dynamically by distinct activity patterns. In dendrites of regularly spiking basket cells, AP-evoked Ca2+ rises were of large amplitude and fast kinetics; however, they decreased with membrane hyperpolarization or following high-frequency firing episodes. In contrast, AP-evoked Ca2+ elevations in dendrites of Schaffer collateral-associated cells exhibited significantly smaller amplitude and slower kinetics, but increased with membrane hyperpolarization. These cell type-specific properties of AP-evoked dendritic Ca2+ signalling were determined by distinct endogenous buffer capacities of the interneurons examined and by specific types of VSCCs recruited by APs during different patterns of activity. Furthermore, AP-evoked Ca2+ transients summated efficiently during theta-like bursting and were associated with the induction of long-term potentiation at inhibitory synapses onto both types of interneurons. Therefore, the cell type-specific profile of AP-evoked dendritic Ca2+ signalling is shaped in an activity-dependent manner, such that the same pattern of hippocampal activity can be differentially translated into dendritic Ca2+ signals in different cell types. However, Cell type-specific differences in Ca2+ signals can be ‘smoothed out’ by changes in neuronal activity, providing a means for common, cell-type-independent forms of synaptic plasticity.
Author: T. Farfel-Becker, E. B. Vitner, S. N. R. Pressey, R. Eilam, J. D. Cooper and A. H. Futerman
Title: Spatial and temporal correlation between neuron loss and neuroinflammation in a mouse model of neuronopathic Gaucher disease
Journal: Human Molecular Genetics Volume: 20 Issue: 7 Pages: 1375-1386 Date: April 1, 2011
Short Title: Spatial and temporal correlation between neuron loss and neuroinflammation in a mouse model of neuronopathic Gaucher disease
DOI: 10.1093/hmg/ddr019
Abstract: Gaucher disease (GD), the most common lysosomal storage disorder, is caused by a deficiency in the lysosomal enzyme glucocerebrosidase (GlcCerase), which results in intracellular accumulation of glucosylceramide (GlcCer). The rare neuronopathic forms of GD are characterized by profound neurological impairment and neuronal cell death, but little is known about the neuropathological changes that underlie these events. We now systematically examine the onset and progression of various neuropathological changes (including microglial activation, astrogliosis and neuron loss) in a mouse model of neuronopathic GD, and document the brain areas that are first affected, which may reflect vulnerability of these areas to GlcCerase deficiency. We also identify neuropathological changes in several brain areas and pathways, such as the substantia nigra reticulata, reticulotegmental nucleus of the pons, cochlear nucleus and the somatosensory system, which could be responsible for some of the neurological manifestations of the human disease. In addition, we establish that microglial activation and astrogliosis are spatially and temporally correlated with selective neuron loss.
Author: T. Furuta, M. Deschênes and T. Kaneko
Title: Anisotropic Distribution of Thalamocortical Boutons in Barrels
Journal: The Journal of Neuroscience Volume: 31 Issue: 17 Pages: 6432-6439 Date: April 27, 2011
Short Title: Anisotropic Distribution of Thalamocortical Boutons in Barrels
DOI: 10.1523/jneurosci.6154-10.2011
Abstract: A characteristic feature of the somatosensory cortex in rodents is the presence of discrete cellular aggregates in layer 4 (barrels) that process input from the mystacial vibrissae. Just like thalamic cells that relay vibrissal information to the barrels, barrel cells display directional preference to whisker motion. The present study examined whether the projection of single thalamic cells into a barrel is consistent with the existence of an orderly map of direction preference. The direction preference of single thalamic cells was assessed, and axonal projections were visualized after juxtacellular labeling with biotinylated dextran. Results show that the terminal field of individual thalamic neurons in a barrel is markedly anisotropic and that the location of boutons with respect to the somatotopic map is either positively or negatively correlated with the angular tuning of the thalamic neuron. These results indicate that angular tuning is not represented across a systematic map with fixed anteroposterior/mediolateral coordinates in a barrel. The actual significance of the direction-dependent segregation of thalamocortical terminals in barrels may only come to light in the context of active sensing.
Author: I. Gvilia, N. Suntsova, B. Angara, D. McGinty and R. Szymusiak
Title: Maturation of sleep homeostasis in developing rats: a role for preoptic area neurons
Journal: American Journal of Physiology – Regulatory, Integrative and Comparative Physiology Volume: 300 Issue: 4 Pages: R885-R894 Date: April 1, 2011
Short Title: Maturation of sleep homeostasis in developing rats: a role for preoptic area neurons
DOI: 10.1152/ajpregu.00727.2010
Abstract: The present study evaluated the hypothesis that developmental changes in hypothalamic sleep-regulatory neuronal circuits contribute to the maturation of sleep homeostasis in rats during the fourth postnatal week. In a longitudinal study, we quantified electrographic measures of sleep during baseline and in response to sleep deprivation (SD) on postnatal days 21/29 (P21/29) and P22/30 (experiment 1). During 24-h baseline recordings on P21, total sleep time (TST) during the light and dark phases did not differ significantly. On P29, TST during the light phase was significantly higher than during the dark phase. Mean duration of non-rapid-eye-movement (NREM) sleep bouts was significantly longer on P29 vs. P21, indicating improved sleep consolidation. On both P22 and P30, rats exhibited increased NREM sleep amounts and NREM electroencephalogram delta power during recovery sleep (RS) compared with baseline. Increased NREM sleep bout length during RS was observed only on P30. In experiment 2, we quantified activity of GABAergic neurons in median preoptic nucleus (MnPN) and ventrolateral preoptic area (VLPO) during SD and RS in separate groups of P22 and P30 rats using c-Fos and glutamic acid decarboxylase (GAD) immunohistochemistry. In P22 rats, numbers of Fos+GAD+ neurons in VLPO did not differ among experimental conditions. In P30 rats, Fos+GAD+ counts in VLPO were elevated during RS. MnPN neuronal activity was state-dependent in P22 rats, but Fos+GAD+ cell counts were higher in P30 rats. These findings support the hypothesis that functional emergence of preoptic sleep-regulatory neurons contributes to the maturation of sleep homeostasis in the developing rat brain.
Author: M. Mańko, R. Geracitano and M. CapognaYear: 2011
Title: Functional connectivity of the main intercalated nucleus of the mouse amygdala
Journal: The Journal of PhysiologyVolume: 589 Issue: 8 Pages: 1911-1925 Date: April 15, 2011
Short Title: Functional connectivity of the main intercalated nucleus of the mouse amygdala
DOI: 10.1113/jphysiol.2010.201475
Abstract: The amygdala plays a key role in the formation and storage of memories associated with emotions. Recently, so-called intercalated clusters of GABAergic neurons in the amygdala have been shown to play an important role in emotional regulation attracting broad interest. We report here novel information on the largest of the intercalated cluster called the main intercalated nucleus of amygdala. Specifically, we study the anatomy, physiology, connectivity and responses to the neuromodulator dopamine of the neurons with the soma in this nucleus. Our results imply that the main intercalated nucleus of the mouse amygdala can participate in the emotional processing.Intercalated cells (ITCs) of the amygdala are clusters of GABAergic cells that surround the basolateral complex of the amygdala (BLA). Growing evidence suggests that ITCs are required for the expression of fear extinction. The main intercalated nucleus (Im) is the largest of the ITC clusters and could also be important for emotional processing. We used whole-cell recordings from Im neurons in acute slices of mouse amygdala. We found that these neurons were medium-sized spiny projection cells. Their passive and active membrane responses were consistent with those previously reported in other ITC clusters. The axon of Im neurons was, in many cases, cut at the slice boundaries, suggesting long-range projections. Axonal branches could be detected in several amygdala nuclei where they made functional synapses. We also functionally studied Im cell inputs. Excitatory postsynaptic currents (eEPSCs) were evoked by the stimulation of the Im, intermediate capsula (IC), external capsula (EC) or BLA, when GABAergic transmission was pharmacologically blocked. An occlusion test indicated that fibres recruited by stimulating Im and IC, or Im and EC were distinct. These eEPSCs had both NMDA and AMPA receptor components. Inhibitory postsynaptic currents (eIPSCs) were evoked after the stimulation of the Im, the EC and the BLA, when glutamatergic transmission was pharmacologically blocked. Furthermore, dopamine reversibly hyperpolarised, and decreased the firing frequency and the input resistance of Im cells via dopamine type 1 receptor. Our data suggest that the Im is functionally connected to other amygdala nuclei and is under neuromodulatory influence. We propose that the Im serves as key neuronal substrate of fear extinction.
Author: H. Mukai, Y. Hatanaka, K. Mitsuhashi, Y. Hojo, Y. Komatsuzaki, R. Sato, G. Murakami, T. Kimoto and S. Kawato
Title: Automated Analysis of Spines from Confocal Laser Microscopy Images: Application to the Discrimination of Androgen and Estrogen Effects on Spinogenesis
Journal: Cerebral Cortex Pages: bhr059 Date: April 28, 2011
Short Title: Automated Analysis of Spines from Confocal Laser Microscopy Images: Application to the Discrimination of Androgen and Estrogen Effects on Spinogenesis
DOI: 10.1093/cercor/bhr059
Abstract: Accurate 3D determination of postsynaptic structures is essential to our understanding memory-related function and pathology in neurons. However, current methods of spine analysis require time-consuming and labor-intensive manual spine identification in large image data sets. Therefore, a realistic implementation of algorithm is necessary to replace manual identification. Here, we describe a new method for the automated detection of spines and dendrites based on analysis of geometrical features. Our “Spiso-3D” software carries out automated dendrite reconstruction and spine detection using both eigenvalue images and information of brightness, avoiding detection of pseudo-spines. To demonstrate the potential application of Spiso-3D automated analysis, we distinguished the rapid effects of androgen and estrogen on rapid modulation of spine head diameter in the hippocampus. These findings advance our understanding of neurotrophic function of brain sex steroids. Our method is expected to be valuable to analyze vast amounts of dendritic spines in neurons in the mammalian cerebral cortex.
Author: S. Sims-Lucas, B. Cusack, V. P. Eswarakumar, J. Zhang, F. Wang and C. M. Bates
Title: Independent roles of Fgfr2 and Frs2α in ureteric epithelium
Journal: Development Volume: 138 Issue: 7 Pages: 1275-1280 Date: April 1, 2011
Short Title: Independent roles of Fgfr2 and Frs2α in ureteric epithelium
DOI: 10.1242/dev.062158
Abstract: Mice with conditional deletion of fibroblast growth factor receptor 2 (Fgfr2) in the ureteric bud using a Hoxb7cre line (Fgfr2UB−/−) develop severe ureteric branching defects; however, ureteric deletion of fibroblast growth factor receptor substrate 2α (Frs2α), a key docking protein that transmits fibroblast growth factor receptor intracellular signaling (Frs2αUB−/−) leads to mild ureteric defects. Mice with point mutations in the Frs2α binding site of Fgfr2 (Fgfr2LR/LR) have normal kidneys. The aim of this study was to determine the relationship between Fgfr2 and Frs2α in the ureteric lineage. Mice with ureteric deletion of both Fgfr2 and Frs2α (Fgfr2/Frs2αUB-/) were compared with Frs2αUB−/− and Fgfr2UB−/− mice. To avoid potential rescue of Fgfr1 forming heterodimers with Fgfr2LR alleles to recruit Frs2α, compound mutant mice were generated with ureteric deletion of Fgfr1 and with Fgfr2LR/LR point mutations (Fgfr1UB−/−Fgfr2LR/LR). At E13.5, three-dimensional reconstructions and histological assessment showed that, whereas Fgfr2UB−/− kidneys had more severe ureteric branching defects than Frs2αUB−/−, Fgfr2UB−/− kidneys were indistinguishable from Fgfr2/Frs2αUB−/−. At later stages, however, Fgfr2/Frs2αUB−/− kidneys were more severely affected than either Fgfr2UB−/− or Frs2αUB−/− kidneys. Taken together, although Fgfr2 and Frs2α have crucial roles in the ureteric lineage, they appear to act separately and additively.
Author: S. C. Jefferson, N. J. Tester and D. R. Howland
Title: Chondroitinase ABC Promotes Recovery of Adaptive Limb Movements and Enhances Axonal Growth Caudal to a Spinal Hemisection
Journal: The Journal of Neuroscience Volume: 31 Issue: 15 Pages: 5710-5720 Date: April 13, 2011
Short Title: Chondroitinase ABC Promotes Recovery of Adaptive Limb Movements and Enhances Axonal Growth Caudal to a Spinal Hemisection
DOI: 10.1523/jneurosci.4459-10.2011
Abstract: A number of studies have shown that chondroitinase ABC (Ch’ase ABC) digestion of inhibitory chondroitin sulfate glycosaminoglycans significantly enhances axonal growth and recovery in rodents following spinal cord injury (SCI). Further, our group has shown improved recovery following SCI in the larger cat model. The purpose of the current study was to determine whether intraspinal delivery of Ch’ase ABC, following T10 hemisections in adult cats, enhances adaptive movement features during a skilled locomotor task and/or promotes plasticity of spinal and supraspinal circuitry. Here, we show that Ch’ase ABC enhanced crossing of a peg walkway post-SCI and significantly improved ipsilateral hindlimb trajectories and integration into a functional forelimb–hindlimb coordination pattern. Recovery of these complex movements was associated with significant increases in neurofilament immunoreactivity immediately below the SCI in the ipsilateral white (p = 0.033) and contralateral gray matter (p = 0.003). Further, the rubrospinal tract is critical in the normal cat during skilled movements that require accurate paw placements and trajectories like those seen during peg walkway crossing. Rubrospinal connections were assessed following Fluoro-Gold injections, caudal to the hemisection. Significantly more retrogradely labeled right (axotomized) red nucleus (RN) neurons were seen in Ch’ase ABC-treated (23%) compared with control-treated cats (8%; p = 0.032) indicating that a larger number of RN neurons in Ch’ase ABC-treated cats had axons below the lesion level. Thus, following SCI, Ch’ase ABC may facilitate axonal growth at the spinal level, enhance adaptive features of locomotion, and affect plasticity of rubrospinal circuitry known to support adaptive behaviors in the normal cat.
Author: G. Naert and S. Rivest
Title: CC Chemokine Receptor 2 Deficiency Aggravates Cognitive Impairments and Amyloid Pathology in a Transgenic Mouse Model of Alzheimer’s Disease
Journal: The Journal of Neuroscience Volume: 31 Issue: 16 Pages: 6208-6220 Date: April 20, 2011
Short Title: CC Chemokine Receptor 2 Deficiency Aggravates Cognitive Impairments and Amyloid Pathology in a Transgenic Mouse Model of Alzheimer’s Disease
DOI: 10.1523/jneurosci.0299-11.2011
Abstract: Circulating monocytoid cells have the ability to infiltrate nervous tissue, differentiate into microglia, and clear amyloid-β (Aβ) from the brain of mouse models of Alzheimer’s disease. Interaction between the chemokine CCL2 and its CC chemokine receptor 2 (CCR2) plays a critical role in the recruitment of inflammatory monocytes into the injured/diseased brain. Here, we show that CCR2 deficiency aggravates mnesic deficits and amyloid pathology in transgenic mice expressing the chimeric mouse/human β-amyloid precursor protein and presenilin 1 (APPSwe/PS1). Indeed, memory impairment was accelerated and enhanced in APPSwe/PS1/CCR2−/− mice. Apparition of cognitive decline occurred earlier (i.e., at 3 months of age before plaque formation) and correlated with intracellular accumulation of soluble oligomeric forms of Aβ. Memory deficits worsened with age and were aggravated in APPSwe/PS1/CCR2−/− mice compared with their respective control groups. Soluble Aβ assemblies increased significantly in APPSwe/PS1 mice in a context of CCR2 deficiency, whereas the plaque load remained relatively similar in the brain of aging APPSwe/PS1 and APPSwe/PS1/CCR2−/− mice. However, CCR2 deficiency stimulated the expression of TGF-β1, TGF-β receptors, and CX3CR1 transcripts in plaque-associated microglia, a pattern that is characteristic of an antiinflammatory subset of myeloid cells. A decreased expression of CCR2 could play a potential role in the etiology of Alzheimer’s disease, a neurodegenerative pathology that could be treated by a genetic upregulation of the transgene in monocytoid cells.
Author: S. Sims-Lucas, B. Cusack, V. P. Eswarakumar, J. Zhang, F. Wang and C. M. Bates
Title: Independent roles of Fgfr2 and Frs2α in ureteric epithelium
Journal: Developmen tVolume: 138 Issue: 7 Pages: 1275-1280 Date: April 1, 2011
Short Title: Independent roles of Fgfr2 and Frs2α in ureteric epithelium
DOI: 10.1242/dev.062158
Abstract: Mice with conditional deletion of fibroblast growth factor receptor 2 (Fgfr2) in the ureteric bud using a Hoxb7cre line (Fgfr2UB−/−) develop severe ureteric branching defects; however, ureteric deletion of fibroblast growth factor receptor substrate 2α (Frs2α), a key docking protein that transmits fibroblast growth factor receptor intracellular signaling (Frs2αUB−/−) leads to mild ureteric defects. Mice with point mutations in the Frs2α binding site of Fgfr2 (Fgfr2LR/LR) have normal kidneys. The aim of this study was to determine the relationship between Fgfr2 and Frs2α in the ureteric lineage. Mice with ureteric deletion of both Fgfr2 and Frs2α (Fgfr2/Frs2αUB-/) were compared with Frs2αUB−/− and Fgfr2UB−/− mice. To avoid potential rescue of Fgfr1 forming heterodimers with Fgfr2LR alleles to recruit Frs2α, compound mutant mice were generated with ureteric deletion of Fgfr1 and with Fgfr2LR/LR point mutations (Fgfr1UB−/−Fgfr2LR/LR). At E13.5, three-dimensional reconstructions and histological assessment showed that, whereas Fgfr2UB−/− kidneys had more severe ureteric branching defects than Frs2αUB−/−, Fgfr2UB−/− kidneys were indistinguishable from Fgfr2/Frs2αUB−/−. At later stages, however, Fgfr2/Frs2αUB−/− kidneys were more severely affected than either Fgfr2UB−/− or Frs2αUB−/− kidneys. Taken together, although Fgfr2 and Frs2α have crucial roles in the ureteric lineage, they appear to act separately and additively.
