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2015
Kohn, E, Katz B, Yasin B, Peters M, Rhodes E, Zaguri R, Weiss S, Minke B.  2015.  Functional cooperation between the IP3 receptor and phospholipase C secures the high sensitivity to light of Drosophila photoreceptors in vivo.. The Journal of neuroscience : the official journal of the Society for Neuroscience. 35(6):2530-46. Abstract
Drosophila phototransduction is a model system for the ubiquitous phosphoinositide signaling. In complete darkness, spontaneous unitary current events (dark bumps) are produced by spontaneous single Gqα activation, while single-photon responses (quantum bumps) arise from synchronous activation of several Gqα molecules. We have recently shown that most of the spontaneous single Gqα activations do not produce dark bumps, because of a critical phospholipase Cβ (PLCβ) activity level required for bump generation. Surpassing the threshold of channel activation depends on both PLCβ activity and cellular [Ca(2+)], which participates in light excitation via a still unclear mechanism. We show here that in IP3 receptor (IP3R)-deficient photoreceptors, both light-activated Ca(2+) release from internal stores and light sensitivity were strongly attenuated. This was further verified by Ca(2+) store depletion, linking Ca(2+) release to light excitation. In IP3R-deficient photoreceptors, dark bumps were virtually absent and the quantum-bump rate was reduced, indicating that Ca(2+) release from internal stores is necessary to reach the critical level of PLCβ catalytic activity and the cellular [Ca(2+)] required for excitation. Combination of IP3R knockdown with reduced PLCβ catalytic activity resulted in highly suppressed light responses that were partially rescued by cellular Ca(2+) elevation, showing a functional cooperation between IP3R and PLCβ via released Ca(2+). These findings suggest that in contrast to the current dogma that Ca(2+) release via IP3R does not participate in light excitation, we show that released Ca(2+) plays a critical role in light excitation. The positive feedback between PLCβ and IP3R found here may represent a common feature of the inositol-lipid signaling.
Livyatan, I, Aaronson Y, Gokhman D, Ashkenazi R, Meshorer E.  2015.  BindDB: An Integrated Database and Webtool Platform for "Reverse-ChIP" Epigenomic Analysis.. Cell stem cell. 17(6):647-8.
Saadon-Grosman, N, Tal Z, Itshayek E, Amedi A, Arzy S.  2015.  Discontinuity of cortical gradients reflects sensory impairment.. Proceedings of the National Academy of Sciences of the United States of America. 112(52):16024-9. Abstract
Topographic maps and their continuity constitute a fundamental principle of brain organization. In the somatosensory system, whole-body sensory impairment may be reflected either in cortical signal reduction or disorganization of the somatotopic map, such as disturbed continuity. Here we investigated the role of continuity in pathological states. We studied whole-body cortical representations in response to continuous sensory stimulation under functional MRI (fMRI) in two unique patient populations-patients with cervical sensory Brown-Séquard syndrome (injury to one side of the spinal cord) and patients before and after surgical repair of cervical disk protrusion-enabling us to compare whole-body representations in the same study subjects. We quantified the spatial gradient of cortical activation and evaluated the divergence from a continuous pattern. Gradient continuity was found to be disturbed at the primary somatosensory cortex (S1) and the supplementary motor area (SMA), in both patient populations: contralateral to the disturbed body side in the Brown-Séquard group and before repair in the surgical group, which was further improved after intervention. Results corresponding to the nondisturbed body side and after surgical repair were comparable with control subjects. No difference was found in the fMRI signal power between the different conditions in the two groups, as well as with respect to control subjects. These results suggest that decreased sensation in our patients is related to gradient discontinuity rather than signal reduction. Gradient continuity may be crucial for somatotopic and other topographical organization, and its disruption may characterize pathological processing.
Barniv, D, Nelken I.  2015.  Auditory Streaming as an Online Classification Process with Evidence Accumulation.. PLoS One. 10(12): e0144788. Abstract
When human subjects hear a sequence of two alternating pure tones, they often perceive it in one of two ways: as one integrated sequence (a single "stream" consisting of the two tones), or as two segregated sequences, one sequence of low tones perceived separately from another sequence of high tones (two "streams"). Perception of this stimulus is thus bistable. Moreover, subjects report on-going switching between the two percepts: unless the frequency separation is large, initial perception tends to be of integration, followed by toggling between integration and segregation phases. The process of stream formation is loosely named "auditory streaming". Auditory streaming is believed to be a manifestation of human ability to analyze an auditory scene, i.e. to attribute portions of the incoming sound sequence to distinct sound generating entities. Previous studies suggested that the durations of the successive integration and segregation phases are statistically independent. This independence plays an important role in current models of bistability. Contrary to this, we show here, by analyzing a large set of data, that subsequent phase durations are positively correlated. To account together for bistability and positive correlation between subsequent durations, we suggest that streaming is a consequence of an evidence accumulation process. Evidence for segregation is accumulated during the integration phase and vice versa; a switch to the opposite percept occurs stochastically based on this evidence. During a long phase, a large amount of evidence for the opposite percept is accumulated, resulting in a long subsequent phase. In contrast, a short phase is followed by another short phase. We implement these concepts using a probabilistic model that shows both bistability and correlations similar to those observed experimentally.
Harikumar, A, Meshorer E.  2015.  Chromatin remodeling and bivalent histone modifications in embryonic stem cells.. EMBO reports. 16(12):1609-19. Abstract
Pluripotent embryonic stem cells (ESCs) are characterized by distinct epigenetic features including a relative enrichment of histone modifications related to active chromatin. Among these is tri-methylation of lysine 4 on histone H3 (H3K4me3). Several thousands of the H3K4me3-enriched promoters in pluripotent cells also contain a repressive histone mark, namely H3K27me3, a situation referred to as "bivalency". While bivalent promoters are not unique to pluripotent cells, they are relatively enriched in these cell types, largely marking developmental and lineage-specific genes which are silent but poised for immediate action. The H3K4me3 and H3K27me3 modifications are catalyzed by lysine methyltransferases which are usually found within, although not entirely limited to, the Trithorax group (TrxG) and Polycomb group (PcG) protein complexes, respectively, but these do not provide selective bivalent specificity. Recent studies highlight the family of ATP-dependent chromatin remodeling proteins as regulators of bivalent domains. Here, we discuss bivalency in general, describe the machineries that catalyze bivalent chromatin domains, and portray the emerging connection between bivalency and the action of different families of chromatin remodelers, namely INO80, esBAF, and NuRD, in pluripotent cells. We posit that chromatin remodeling proteins may enable "bivalent specificity", often selectively acting on, or selectively depleted from, bivalent domains.
Libster, AM, Title B, Yarom Y.  2015.  Corticotropin-releasing factor increases Purkinje neuron excitability by modulating sodium, potassium, and Ih currents.. Journal of neurophysiology. 114(6):3339-50. Abstract
Corticotropin-releasing factor (CRF) is a neuromodulator closely associated with stress responses. It is synthesized and released in the central nervous system by various neurons, including neurons of the inferior olive. The targets of inferior olivary neurons, the cerebellar Purkinje neurons (PNs), are endowed with CRF receptors. CRF increases the excitability of PNs in vivo, but the biophysical mechanism is not clear. Here we examine the effect of CRF on the firing properties of PNs using acute rat cerebellar slices. CRF increased the PN firing rate, regardless of whether they were firing tonically or switching between firing and quiescent periods. Current- and voltage-clamp experiments showed that the increase in firing rate was associated with a voltage shift of the activation curve of the persistent sodium current and hyperpolarizing-activated current, as well as activation of voltage-dependent potassium current. The multiple effects on various ionic currents, which are in agreement with the possibility that activation of CRF receptors triggers several intracellular pathways, are manifested as an increase excitability of PN.
Zylbertal, A, Kahan A, Ben-Shaul Y, Yarom Y, Wagner S.  2015.  Prolonged Intracellular Na+ Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells.. PLoS biology. 13(12):e1002319. Abstract
Persistent activity has been reported in many brain areas and is hypothesized to mediate working memory and emotional brain states and to rely upon network or biophysical feedback. Here, we demonstrate a novel mechanism by which persistent neuronal activity can be generated without feedback, relying instead on the slow removal of Na+ from neurons following bursts of activity. We show that mitral cells in the accessory olfactory bulb (AOB), which plays a major role in mammalian social behavior, may respond to a brief sensory stimulation with persistent firing. By combining electrical recordings, Ca2+ and Na+ imaging, and realistic computational modeling, we explored the mechanisms underlying the persistent activity in AOB mitral cells. We found that the exceptionally slow inward current that underlies this activity is governed by prolonged dynamics of intracellular Na+ ([Na+]i), which affects neuronal electrical activity via several pathways. Specifically, elevated dendritic [Na+]i reverses the Na+-Ca2+ exchanger activity, thus modifying the [Ca2+]i set-point. This process, which relies on ubiquitous membrane mechanisms, is likely to play a role in other neuronal types in various brain regions.
Joshua, M, Tokiyama S, Lisberger SG.  2015.  Interactions between target location and reward size modulate the rate of microsaccades in monkeys.. Journal of neurophysiology. :jn.00401.2015. Abstract
We have studied how rewards modulate the occurrence of microsaccades by manipulating the size of an expected reward and the location of the cue that sets the expectations for future reward. We found an interaction between the size of the reward and the location of the cue. When monkeys fixated on a cue that signaled the size of future reward, the frequency of microsaccades was higher if the monkey expected a large versus a small reward. When the cue was presented at a site in the visual field that was remote from the position of fixation, reward size had the opposite effect: the frequency of microsaccades was lower when the monkey was expecting a large reward. The strength of pursuit initiation also was affected by rewards size and by the presence of microsaccades just before the onset of target motion. The gain of pursuit initiation increased with reward size and decreased when microsaccades occurred just before or after the onset of target motion. The effect of the reward size on pursuit initiation was much larger than any indirect effects reward might cause through modulation of the rate of microsaccades. We found only a weak relationship between microsaccade direction and the location of the exogenous cue relative to fixation position, even in experiments where the location of the cue indicated the direction of target motion. Our results indicate that the expectation of reward is a powerful modulator of the occurrence of microsaccades, perhaps through attentional mechanisms.
McKyton, A, Ben-Zion I, Doron R, Zohary E.  2015.  The Limits of Shape Recognition following Late Emergence from Blindness.. Current biology : CB. Abstract
Visual object recognition develops during the first years of life [1]. But what if one is deprived of vision during early post-natal development? Shape information is extracted using both low-level cues (e.g., intensity- or color-based contours) and more complex algorithms that are largely based on inference assumptions (e.g., illumination is from above, objects are often partially occluded) [2]. Previous studies, testing visual acuity using a 2D shape-identification task (Lea symbols), indicate that contour-based shape recognition can improve with visual experience, even after years of visual deprivation from birth [3]. We hypothesized that this may generalize to other low-level cues (shape, size, and color), but not to mid-level functions (e.g., 3D shape from shading) that might require prior visual knowledge. To that end, we studied a unique group of subjects in Ethiopia that suffered from an early manifestation of dense bilateral cataracts and were surgically treated only years later. Our results suggest that the newly sighted rapidly acquire the ability to recognize an odd element within an array, on the basis of color, size, or shape differences. However, they are generally unable to find the odd shape on the basis of illusory contours, shading, or occlusion relationships. Little recovery of these mid-level functions is seen within 1 year post-operation. We find that visual performance using low-level cues is relatively robust to prolonged deprivation from birth. However, the use of pictorial depth cues to infer 3D structure from the 2D retinal image is highly susceptible to early and prolonged visual deprivation.
Roth, ZN, Zohary E.  2015.  Position and Identity Information Available in fMRI Patterns of Activity in Human Visual Cortex.. The Journal of neuroscience : the official journal of the Society for Neuroscience. 35(33):11559-71. Abstract
Parietal cortex is often implicated in visual processing of actions. Action understanding is essentially abstract, specific to the type or goal of action, but greatly independent of variations in the perceived position of the action. If certain parietal regions are involved in action understanding, then we expect them to show these generalization and selectivity properties. However, additional functions of parietal cortex, such as self-action control, may impose other demands by requiring an accurate representation of the location of graspable objects. Therefore, the dimensions along which responses are modulated may indicate the functional role of specific parietal regions. Here, we studied the degree of position invariance and hand/object specificity during viewing of tool-grasping actions. To that end, we characterize the information available about location, hand, and tool identity in the patterns of fMRI activation in various cortical areas: early visual cortex, posterior intraparietal sulcus, anterior superior parietal lobule, and the ventral object-specific lateral occipital complex. Our results suggest a gradient within the human dorsal stream: along the posterior-anterior axis, position information is gradually lost, whereas hand and tool identity information is enhanced. This may reflect a gradual transformation of visual input from an initial retinotopic representation in early visual areas to an abstract, position-invariant representation of viewed action in anterior parietal cortex.
Duan, Y, Norcia AM, Yeatman JD, Mezer A.  2015.  The Structural Properties of Major White Matter Tracts in Strabismic Amblyopia.. Investigative ophthalmology & visual science. 56(9):5152-60. Abstract
In order to better understand whether white matter structural deficits are present in strabismic amblyopia, we performed a survey of the tissue properties of 28 major white matter tracts using diffusion and quantitative magnetic resonance imaging approaches.
Shofty, B, Mauda-Havakuk M, Weizman L, Constantini S, Ben-Bashat D, Dvir R, Pratt L-T, Joskowicz L, Kesler A, Yalon M et al..  2015.  The effect of chemotherapy on optic pathway gliomas and their sub-components: A volumetric MR analysis study.. Pediatric blood & cancer. 62(8):1353-9. Abstract
Optic pathway gliomas (OPG) represent 5% of pediatric brain tumors and compose a major therapeutic dilemma to the treating physicians. While chemotherapy is widely used for these tumors, our ability to predict radiological response is still lacking. In this study, we use volumetric imaging to examine in detail the long-term effect of chemotherapy on the tumor as well as its various sub-components.
Schechtman, E, Adler A, Deffains M, Gabbay H, Katabi S, Mizrahi A, Bergman H.  2015.  Coinciding decreases in discharge rate suggest that spontaneous pauses in firing of external pallidum neurons are network driven.. The Journal of neuroscience : the official journal of the Society for Neuroscience. 35(17):6744-51. Abstract
The external segment of the globus pallidus (GPe) is one of the core nuclei of the basal ganglia, playing a major role in normal control of behavior and in the pathophysiology of basal ganglia-related disorders such as Parkinson's disease. In vivo, most neurons in the GPe are characterized by high firing rates (50-100 spikes/s), interspersed with long periods (∼0.6 s) of complete silence, which are termed GPe pauses. Previous physiological studies of single and pairs of GPe neurons have failed to fully disclose the physiological process by which these pauses originate. We examined 1001 simultaneously recorded pairs of high-frequency discharge GPe cells recorded from four monkeys during task-irrelevant periods, considering the activity in one cell while the other is pausing. We found that pauses (n = 137,278 pauses) coincide with a small yet significant reduction in firing rate (0.78 ± 0.136 spikes/s) in other GPe cells. Additionally, we found an increase in the probability of the simultaneously recorded cell to pause during the pause period of the "trigger" cell. Importantly, this increase in the probability to pause at the same time does not account for the reduction in firing rate by itself. Modeling of GPe cells as class 2 excitability neurons (Hodgkin, 1948) with common external inputs can explain our results. We suggest that common inputs decrease the GPe discharge rate and lead to a bifurcation phenomenon (pause) in some of the GPe neurons.
Tsuriel, S, Gudes S, Draft RW, Binshtok AM*, Lichtman JW*, corresponding authors *.  2015.  Multispectral labeling technique to map many neighboring axonal projections in the same tissue. Nature Methods. Abstract
We describe a method to map the location of axonal arbors of many individual neurons simultaneously via the spectral properties of retrogradely transported dye-labeled vesicles. We inject overlapping regions of an axon target area with three or more different colored retrograde tracers. On the basis of the combinations and intensities of the colors in the individual vesicles transported to neuronal somata, we calculate the projection sites of each neuron's axon. This neuronal positioning system (NPS) enables mapping of many axons in a simple automated way. In our experiments, NPS combined with spectral (Brainbow) labeling of the input to autonomic ganglion cells showed that the locations of ganglion cell projections to a mouse salivary gland related to the identities of their preganglionic axonal innervation. NPS could also delineate projections of many axons simultaneously in the mouse central nervous system.
Kfir, N, Lev-Maor G, Glaich O, Alajem A, Datta A, Sze SK, Meshorer E, Ast G.  2015.  SF3B1 Association with Chromatin Determines Splicing Outcomes.. Cell reports. Abstract
Much remains unknown concerning the mechanism by which the splicing machinery pinpoints short exons within intronic sequences and how splicing factors are directed to their pre-mRNA targets. One probable explanation lies in differences in chromatin organization between exons and introns. Proteomic, co-immunoprecipitation, and sedimentation analyses described here indicate that SF3B1, an essential splicing component of the U2 snRNP complex, is strongly associated with nucleosomes. ChIP-seq and RNA-seq analyses reveal that SF3B1 specifically binds nucleosomes located at exonic positions. SF3B1 binding is enriched at nucleosomes positioned over short exons flanked by long introns that are also characterized by differential GC content between exons and introns. Disruption of SF3B1 binding to such nucleosomes affects splicing of these exons similarly to SF3B1 knockdown. Our findings suggest that the association of SF3B1 with nucleosomes is functionally important for splice-site recognition and that SF3B1 conveys splicing-relevant information embedded in chromatin structure.
Travis, KE, Golden NH, Feldman HM, Solomon M, Nguyen J, Mezer A, Yeatman JD, Dougherty RF.  2015.  Abnormal white matter properties in adolescent girls with anorexia nervosa.. NeuroImage. Clinical. 9:648-59. Abstract
Anorexia nervosa (AN) is a serious eating disorder that typically emerges during adolescence and occurs most frequently in females. To date, very few studies have investigated the possible impact of AN on white matter tissue properties during adolescence, when white matter is still developing. The present study evaluated white matter tissue properties in adolescent girls with AN using diffusion MRI with tractography and T1 relaxometry to measure R1 (1/T1), an index of myelin content. Fifteen adolescent girls with AN (mean age = 16.6 years ± 1.4) were compared to fifteen age-matched girls with normal weight and eating behaviors (mean age = 17.1 years ± 1.3). We identified and segmented 9 bilateral cerebral tracts (18) and 8 callosal fiber tracts in each participant's brain (26 total). Tract profiles were generated by computing measures for fractional anisotropy (FA) and R1 along the trajectory of each tract. Compared to controls, FA in the AN group was significantly decreased in 4 of 26 white matter tracts and significantly increased in 2 of 26 white matter tracts. R1 was significantly decreased in the AN group compared to controls in 11 of 26 white matter tracts. Reduced FA in combination with reduced R1 suggests that the observed white matter differences in AN are likely due to reductions in myelin content. For the majority of tracts, group differences in FA and R1 did not occur within the same tract. The present findings have important implications for understanding the neurobiological factors underlying white matter changes associated with AN and invite further investigations examining associations between white matter properties and specific physiological, cognitive, social, or emotional functions affected in AN.
Barbash, S.  2015.  Dynamics of social network structure for Alzheimer and Lymphoma scientific communities.. Biology direct. 10(1):6. Abstract
It is generally assumed that sociology affects scientific progress but specific examples of this assumption are hard to find. We examined this hypothesis by comparing the social network structure and its dynamics over the last 16 years, for two common human diseases; Alzheimer's disease, for which there has been very little therapeutic progress, and Lymphoma, were there has been significant therapeutic progress. We found that the Alzheimer's research community is more interlinked ('dense') and more 'cliquish' than that of Lymphoma and suggest that this could affect its scientific progress.
Kalcheim, C.  2015.  Epithelial-Mesenchymal Transitions during Neural Crest and Somite Development.. Journal of clinical medicine. 5(1) Abstract
Epithelial-to-mesenchymal transition (EMT) is a central process during embryonic development that affects selected progenitor cells of all three germ layers. In addition to driving the onset of cellular migrations and subsequent tissue morphogenesis, the dynamic conversions of epithelium into mesenchyme and vice-versa are intimately associated with the segregation of homogeneous precursors into distinct fates. The neural crest and somites, progenitors of the peripheral nervous system and of skeletal tissues, respectively, beautifully illustrate the significance of EMT to the above processes. Ongoing studies progressively elucidate the gene networks underlying EMT in each system, highlighting the similarities and differences between them. Knowledge of the mechanistic logic of this normal ontogenetic process should provide important insights to the understanding of pathological conditions such as cancer metastasis, which shares some common molecular themes.
Rokem, A, Yeatman JD, Pestilli F, Kay KN, Mezer A, van der Walt S, Wandell BA.  2015.  Evaluating the accuracy of diffusion MRI models in white matter.. PloS one. 10(4):e0123272. Abstract
Models of diffusion MRI within a voxel are useful for making inferences about the properties of the tissue and inferring fiber orientation distribution used by tractography algorithms. A useful model must fit the data accurately. However, evaluations of model-accuracy of commonly used models have not been published before. Here, we evaluate model-accuracy of the two main classes of diffusion MRI models. The diffusion tensor model (DTM) summarizes diffusion as a 3-dimensional Gaussian distribution. Sparse fascicle models (SFM) summarize the signal as a sum of signals originating from a collection of fascicles oriented in different directions. We use cross-validation to assess model-accuracy at different gradient amplitudes (b-values) throughout the white matter. Specifically, we fit each model to all the white matter voxels in one data set and then use the model to predict a second, independent data set. This is the first evaluation of model-accuracy of these models. In most of the white matter the DTM predicts the data more accurately than test-retest reliability; SFM model-accuracy is higher than test-retest reliability and also higher than the DTM model-accuracy, particularly for measurements with (a) a b-value above 1000 in locations containing fiber crossings, and (b) in the regions of the brain surrounding the optic radiations. The SFM also has better parameter-validity: it more accurately estimates the fiber orientation distribution function (fODF) in each voxel, which is useful for fiber tracking.
Hochstein, S, Pavlovskaya M, Bonneh YS, Soroker N.  2015.  Global statistics are not neglected.. Journal of vision. 15(4):7. Abstract
In the framework of Reverse Hierarchy Theory it was suggested that initial vision at a glance brings the gist of the scene to conscious perception using explicit high cortical level representations, which are initially built by implicit bottom-up processing (Hochstein & Ahissar, 2002). Only later return to lower cortical level representations introduces local details to conscious perception. Global statistics of similar elements are perceived rapidly and accurately, suggesting they are included in the initial perception of the gist of the scene, not depending on prior conscious perception of local details. Patients with unilateral spatial neglect have difficulty responding to elements in their contralesional hemifield. However, this deficit is especially pronounced for tasks that require focused attention, i.e., are dependent on the reverse-hierarchy return. We review recent studies that indicate that perception of global statistics is among the spread attention tasks that are somewhat spared from this deficit. Combining these results, we suggest that perhaps the function of global statistics perception might include serving as a basic percept required for finding salient deviants from the mean, as in rapid odd element feature search paradigms, and perhaps subsequently focusing attention to them.
Mattout, A, Aaronson Y, Sailaja B S, Raghu Ram EV, Harikumar A, Mallm J-P, Sim K H, Nissim-Rafinia M, Supper E, Singh PB et al..  2015.  Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells.. Genome biology. 16:213. Abstract
Pluripotent embryonic stem cells (ESCs) have the unique ability to differentiate into every cell type and to self-renew. These characteristics correlate with a distinct nuclear architecture, epigenetic signatures enriched for active chromatin marks and hyperdynamic binding of structural chromatin proteins. Recently, several chromatin-related proteins have been shown to regulate ESC pluripotency and/or differentiation, yet the role of the major heterochromatin proteins in pluripotency is unknown.
Ramaswamy, S, et al.  2015.  The neocortical microcircuit collaboration portal: a resource for rat somatosensory cortex.. Frontiers in neural circuits. 9:44.
Ankri, L, Husson Z, Pietrajtis K, Proville R, Léna C, Yarom Y, Dieudonné S, Uusisaari M Y.  2015.  A novel inhibitory nucleo-cortical circuit controls cerebellar Golgi cell activity.. eLife. 4 Abstract
The cerebellum, a crucial center for motor coordination, is composed of a cortex and several nuclei. The main mode of interaction between these two parts is considered to be formed by the inhibitory control of the nuclei by cortical Purkinje neurons. We now amend this view by showing that inhibitory GABA-glycinergic neurons of the cerebellar nuclei (CN) project profusely into the cerebellar cortex, where they make synaptic contacts on a GABAergic subpopulation of cerebellar Golgi cells. These spontaneously firing Golgi cells are inhibited by optogenetic activation of the inhibitory nucleo-cortical fibers both in vitro and in vivo. Our data suggest that the CN may contribute to the functional recruitment of the cerebellar cortex by decreasing Golgi cell inhibition onto granule cells.
Carmel, M S, Kahane N, Oberman F, Miloslavski R, Sela-Donenfeld D, Kalcheim C, Yisraeli JK.  2015.  A Novel Role for VICKZ Proteins in Maintaining Epithelial Integrity during Embryogenesis.. PloS one. 10(8):e0136408. Abstract
VICKZ (IGF2BP1,2,3/ZBP1/Vg1RBP/IMP1,2,3) proteins bind RNA and help regulate many RNA-mediated processes. In the midbrain region of early chick embryos, VICKZ is expressed in the neural folds and along the basal surface of the neural epithelium, but, upon neural tube closure, is down-regulated in prospective cranial neural crest (CNC) cells, concomitant with their emigration and epithelial-to-mesenchymal transition (EMT). Electroporation of constructs that modulate cVICKZ expression demonstrates that this down-regulation is both necessary and sufficient for CNC EMT. These results suggest that VICKZ down-regulation in CNC cell-autonomously promotes EMT and migration. Reduction of VICKZ throughout the embryo, however, inhibits CNC migration non-cell-autonomously, as judged by transplantation experiments in Xenopus embryos.
Busche, M A, Kekuš M, Adelsberger H, Noda T, Förstl H, Nelken I, Konnerth A.  2015.  Rescue of long-range circuit dysfunction in Alzheimer's disease models.. Nature Neuroscience. Abstract
Alzheimer's disease (AD) is associated with defects of synaptic connectivity. Such defects may not be restricted to local neuronal interactions but may extend to long-range brain activities, such as slow-wave oscillations that are particularly prominent during non-rapid eye movement (non-REM) sleep and are important for integration of information across distant brain regions involved in memory consolidation. There is increasing evidence that sleep is often impaired in AD, but it is unclear whether this impairment is directly related to amyloid-β (Aβ) pathology. Here we demonstrate that slow-wave activity is severely altered in the neocortex, thalamus and hippocampus in mouse models of AD amyloidosis. Most notably, our results reveal an Aβ-dependent impairment of slow-wave propagation, which causes a breakdown of the characteristic long-range coherence of slow-wave activity. The finding that the impairment can be rescued by enhancing GABAAergic inhibition identifies a synaptic mechanism underlying Aβ-dependent large-scale circuit dysfunction.