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Enrico Mugnaini - One of the best experts on this subject based on the ideXlab platform.
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the Unipolar Brush Cell a remarkable neuron finally receiving deserved attention
Brain Research Reviews, 2011Co-Authors: Enrico Mugnaini, Gabriella Sekerkova, Marco MartinaAbstract:Unipolar Brush Cells (UBC) are small, glutamatergic neurons residing in the granular layer of the cerebellar cortex and the granule Cell domain of the cochlear nuclear complex. Recent studies indicate that this neuronal class consists of three or more subsets characterized by distinct chemical phenotypes, as well as by intrinsic properties that may shape their synaptic responses and firing patterns. Yet, all UBCs have a unique morphology, as both the dendritic Brush and the large endings of the axonal branches participate in the formation of glomeruli. Although UBCs and granule Cells may share the same excitatory and inhibitory inputs, the two Cell types are distinctively differentiated. Typically, whereas the granule Cell has 4-5 dendrites that are innervated by different mossy fibers, and an axon that divides only once to form parallel fibers after ascending to the molecular layer, the UBC has but one short dendrite whose Brush engages in synaptic contact with a single mossy fiber terminal, and an axon that branches locally in the granular layer; branches of UBC axons form a non-canonical, cortex-intrinsic category of mossy fibers synapsing with granule Cells and other UBCs. This is thought to generate a feed-forward amplification of single mossy fiber afferent signals that would reach the overlying Purkinje Cells via ascending granule Cell axons and their parallel fibers. In sharp contrast to other classes of cerebellar neurons, UBCs are not distributed homogeneously across cerebellar lobules, and subsets of UBCs also show different, albeit overlapping, distributions. UBCs are conspicuously rare in the expansive lateral cerebellar areas targeted by the cortico-ponto-cerebellar pathway, while they are a constant component of the vermis and the flocculonodular lobe. The presence of UBCs in cerebellar regions involved in the sensorimotor processes that regulate body, head and eye position, as well as in regions of the cochlear nucleus that process sensorimotor information suggests a key role in these critical functions; it also invites further efforts to clarify the Cellular biology of the UBCs and their specific functions in the neuronal microcircuits in which they are embedded. High density of UBCs in specific regions of the cerebellar cortex is a feature largely conserved across mammals and suggests an involvement of these neurons in fundamental aspects of the input/output organization as well as in clinical manifestation of focal cerebellar disease.
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Vesicular glutamate transporters VGLUT1 and VGLUT2 define two subsets of Unipolar Brush Cells in organotypic cultures of mouse vestibulocerebellum
Neuroscience, 2003Co-Authors: Maria-grazia Nunzi, Marco Joseph Russo, Enrico MugnainiAbstract:Abstract Different isoforms of a vesicular glutamate transporter (VGLUT) mediate glutamate uptake into synaptic vesicles of excitatory neurons. There is agreement that the VGLUTs are differentially expressed in brain, and that two isoforms, VGLUT1 and VGLUT2, are localized to excitatory axon terminals in the cerebellar cortex. While granule Cells express solely VGLUT1, there is no report about the VGLUT(s) of the Unipolar Brush Cell (UBC), the second type of glutamatergic interneuron residing in the cerebellar granular layer. In the mouse, UBCs are particularly numerous in the uvula (lobule IX) and nodulus (lobule X). These folia contain two distinct subsets of UBCs: one kind expresses the calcium-binding protein calretinin (CR), and the other kind expresses the metabotropic glutamate receptor (mGluR) 1α. UBCs give rise to an extensive system of intrinsic mossy fibers (MF), whose terminals innervate granule Cells and other UBCs, altogether similar to those formed by the extrinsic MFs. The presence of both extrinsic and intrinsic MFs in the vestibulocerebellum makes it difficult to determine which type of VGLUT is contained in MFs formed by the UBC axons. Hence, the nodulus was isolated from sagittal cerebellar slices from postnatal day 10 mice, and cultured for 15–20 days in vitro . Double immunofluorescence and confocal microscopy showed that mossy terminals of CR-positive (CR + ) UBCs were immunoreactive for VGLUT1 and VGLUT2, while mossy terminals of mGluR1α-positive (mGluR1α + ) UBCs were provided with VGLUT1 only. Moreover, CR + dendritic Brushes were contacted by mossy terminals provided with both transporters, while mGluR1α + dendritic Brushes were contacted by mossy terminals immunopositive for VGLUT1 and immunonegative for VGLUT2. These data indicate that the two UBC subsets use different modalities of vesicular glutamate storage and form separate networks. We consider it possible that expressions of CR with VGLUT1/VGLUT2 and mGluR1α + with VGLUT1 in the two subsets of vestibulocerebellar UBCs are determined by specific vestibular inputs, carried by groups of primary and/or secondary vestibular afferents.
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differential expression of calretinin and metabotropic glutamate receptor mglur1α defines subsets of Unipolar Brush Cells in mouse cerebellum
The Journal of Comparative Neurology, 2002Co-Authors: Maria-grazia Nunzi, Ryuichi Shigemoto, Enrico MugnainiAbstract:The Unipolar Brush Cell (UBC) is a type of glutamatergic interneuron in the granular layer of the cerebellum. The UBC Brush and a single mossy fiber (MF) terminal contact each other within a cerebellar glomerulus, forming a giant synapse. Many UBCs receive input from extrinsic MFs, whereas others are innervated by intrinsic mossy terminals formed by the axons of other UBCs. In all mammalian species so far examined, the vestibulocerebellum is enriched of UBCs that are strongly immunoreactive for the calcium binding protein calretinin (CR) in both the somatodendritic and axonal compartment. UBCs have postsynaptic ionotropic glutamate receptors and extrasynaptic metabotropic glutamate receptors that immunocytochemically highlight their somatodendritic compartment and Brush, respectively. In this study on the mouse cerebellum, we present evidence that immunoreactivities to CR and mGluR1α define two distinct UBC subsets with partly overlapping distributions in lobule X (the nodulus). In sections double-labeled for CR and mGluR1α, the patterns of distributions of CR+/mGluR1α− UBCs and CR−/mGluR1α+ UBCs differed along the mediolateral and dorsoventral axes of the folium. Moreover, mGluR1α+ UBCs outnumbered CR+ UBCs. Both UBC subsets were mGluR2/3, GluR2/3, and NMDAR1 immunoreactive. The different distribution patterns of the two UBC subsets within lobule X suggest that expression of CR or mGluR1α by UBCs may be afferent-specific and related to the terminal fields of different vestibular MF afferents. J. Comp. Neurol. 451:189–199, 2002. © 2002 Wiley-Liss, Inc.
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Cerebellar Unipolar Brush Cells are targets of primary vestibular afferents: an experimental study in the gerbil
Experimental Brain Research, 2001Co-Authors: Maria R. Diño, Adrian A. Perachio, Enrico MugnainiAbstract:The Unipolar Brush Cell (UBC) is an excitatory glutamatergic interneuron, situated in the cerebellar granular layer, that itself receives excitatory synaptic input on its dendritic Brush from a single mossy fiber terminal in the form of a giant glutamatergic synapse. The UBC axon branches within the granular layer, giving rise to large terminals that synapse with both granule Cell and UBC dendrites within glomeruli and resemble in morphological and functional terms those formed by extrinsic mossy fibers. So far, the only demonstrated extrinsic afferents to the UBC are the choline acetyltransferase (ChAT)-positive mossy fibers, some of which originate from the medial and descending vestibular nuclei. To ascertain whether UBCs are innervated by primary vestibular fibers, we performed a tract-tracing light and electron microscopic study of the vestibulocerebellum in gerbils. Macular and canal vestibular end-organs were individually labeled by injection of biotinylated dextran amine. After an appropriate survival time, gerbils were then processed for light and electron microscopic analysis of central vestibular projections. In the nodulus and uvula, labeled primary vestibular fibers formed mossy terminals synapsing with both granule Cells and UBCs in all of the injected gerbils. Thus, innervation of UBCs by extrinsic mossy fibers carrying static and dynamic vestibular signals represents the first synapse of networks that contribute a powerful form of distributed excitation in the granular layer.
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Enrichment of Unipolar Brush Cell-like neurons in primary rat cerebellar cultures.
Anatomy and embryology, 2001Co-Authors: Roberta Anelli, Enrico MugnainiAbstract:Unipolar Brush Cells are a distinct class of excitatory interneurons situated in the granular layer of the cerebellar cortex, where they form giant synapses with individual mossy fiber terminals. We have previously shown that primary cerebellar Cell cultures from embryonic and postnatal rodents contain neurons displaying morphological and chemical phenotypes characteristic of Unipolar Brush Cells in situ, including intense staining with calretinin antiserum. In cultures from both embryonic and postnatal rats, the large majority of calretinin-positive neurons are Unipolar Brush Cells, while granule Cells are usually calretinin-negative. A small percentage of putative Golgi/ Lugaro Cells also express calretinin. We demonstrate here that the developmental stage of the source tissue, the concentration of potassium in the medium, and treatment with glutamate after differentiation have substantial effects on the density of putative Unipolar Brush Cells in the cultures. In dissociated cultures obtained from embryos at gestation day E18 and E20 and from pups at postnatal day P0, P2, P5, P8, and P10 grown in 25 mM KCl, the percentage calretinin-positive Cells progressively decreases from 24% to 0.1% of total Cells. In cultures from E20 embryos grown in physiological potassium (5 mM KCl), calretinin-positive Cells are enriched to approximately 60% of total Cells, while the majority of calretinin-negative Cells die. In embryonic cultures exposed to high concentrations of glutamate after 12 days in vitro, calretinin-positive neurons have a survival advantage over calretinin-negative Cells and represent up to 83% of total Cells.
Maria R. Diño - One of the best experts on this subject based on the ideXlab platform.
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commentary on e mugnaini and a floris the Unipolar Brush Cell a neglected neuron of the mammalian cerebellar cortex j comp neurol 339 174 180 1994
The Cerebellum, 2015Co-Authors: Maria R. Diño, Gabriella Sekerkova, Marco MartinaAbstract:One of the accomplishments of Enrico’s laboratory in the late 1980s—then at the University of Connecticut in Storrs—was demonstrating that cerebellar-like neuronal microcircuits exist in the acoustic brainstem [1]. This was done by coupling classic neuroanatomical methods (such as electron microscopy and tract tracing) to what were then two novel techniques: immunocytochemical Cell-specific neuronal labeling and the use of transgenicmice. Thus, in the early 1990s, the laboratory focused on clarifying the precise organization, input and output, and evolutionary significance of the recently identified cerebellar-like microcircuit in the mammalian dorsal cochlear nuclear complex (DCN). At the same time, Enrico’s laboratory continued its long-standing interest in cerebellar organization and development (Enrico’s cerebellar grant was continuously funded for what might be a record-setting 38 years [2]). Like most serendipitous scientific discoveries, the Unipolar Brush Cell’s (UBC’s) identification was both unforeseen and unplanned, but nevertheless the by-product of a sagacious and prepared mind. Because the Purkinje Cell markers used in the DCN studies were mostly calcium-binding proteins (calbindin, PEP-19, and parvalbumin), Enrico constantly reached out to potential collaborators who worked with this family of proteins. Among them was David Jacobowitz from the NIH, who sent us antibodies to the calcium-binding protein calretinin, which turned out to be a Cell-marker for what we now know as one of the UBC subtypes [3]. As a beginning graduate student, I had no notion of what we had found. But Enrico immediately put it into context, recalling studies describing novel cerebellar neurons primarily localized to the vestibulocerebellum: Altman and Bayer’s pale Cells [4], Susan Hockfield’s Rat-302 Cells [5], Munoz’monodendritic neurons [6], and the secretogranin-positive Cells described by Cozzi et al. [7]. Bringing to bear his expertise and encyclopedic knowledge of classic neuroanatomy and electron microscopy, Enrico turned his attention to the UBC’s ultrastructure and synaptology [8] and quickly realized that previous studies (including his own) had already described UBC features but mistakenly attributed them to other cerebellar Cell types. For example, the Bhairy dendrites^ and ringlet subunits that he had previously described for Golgi Cells of the cat cerebellum [9], and the giant mossy fiber Ben marron^ synapse previously described on the postsynaptic Golgi II neuron by ChanPalay and Palay [10]: all of these turned out to be UBC hallmarks. Other telltale features of the UBC revealed by a combination of preand post-embedding immunoelectron microscopy included a high density of large dense-cored vesicles; an abundance of high molecular weight neurofilament protein, whose dephosphorylated variant was later identified as the Rat-302 protein [11]; a postsynaptic microfilamentous actin web under the giant mossy fiber-UBC synapse [12]; and the The Introduction article of Cerebellar Classic XI is available at http:// dx.doi.org/10.1007/s12311-015-0661-0
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Cerebellar Unipolar Brush Cells are targets of primary vestibular afferents: an experimental study in the gerbil
Experimental Brain Research, 2001Co-Authors: Maria R. Diño, Adrian A. Perachio, Enrico MugnainiAbstract:The Unipolar Brush Cell (UBC) is an excitatory glutamatergic interneuron, situated in the cerebellar granular layer, that itself receives excitatory synaptic input on its dendritic Brush from a single mossy fiber terminal in the form of a giant glutamatergic synapse. The UBC axon branches within the granular layer, giving rise to large terminals that synapse with both granule Cell and UBC dendrites within glomeruli and resemble in morphological and functional terms those formed by extrinsic mossy fibers. So far, the only demonstrated extrinsic afferents to the UBC are the choline acetyltransferase (ChAT)-positive mossy fibers, some of which originate from the medial and descending vestibular nuclei. To ascertain whether UBCs are innervated by primary vestibular fibers, we performed a tract-tracing light and electron microscopic study of the vestibulocerebellum in gerbils. Macular and canal vestibular end-organs were individually labeled by injection of biotinylated dextran amine. After an appropriate survival time, gerbils were then processed for light and electron microscopic analysis of central vestibular projections. In the nodulus and uvula, labeled primary vestibular fibers formed mossy terminals synapsing with both granule Cells and UBCs in all of the injected gerbils. Thus, innervation of UBCs by extrinsic mossy fibers carrying static and dynamic vestibular signals represents the first synapse of networks that contribute a powerful form of distributed excitation in the granular layer.
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Postnatal differentiation of Unipolar Brush Cells and mossy fiber-Unipolar Brush Cell synapses in rat cerebellum.
Neuroscience, 2001Co-Authors: F Morin, Maria R. Diño, Enrico MugnainiAbstract:Abstract The Unipolar Brush Cells are excitatory, cerebellar granular layer interneurons that receive mossy fiber input on their dendritic Brushes in the form of a giant glutamatergic synapse. We investigated the postnatal development of the Brush of the Unipolar Brush Cell in lobules IX and X by light microscopy and defined the maturation of mossy fiber-Unipolar Brush Cell synapses and mossy fiber-granule Cell synapses by electron microscopy using calretinin immunocytochemistry to identify Unipolar Brush Cells. During the first postnatal week, Unipolar Brush Cells possessed one or two short, branched dendrites. The Brush differentiated primarily during the successive 21 postnatal (P) days, during which it underwent progressive maturation. This developmental process was subdivided into stages 1–4, which were descriptively termed protodendritic Unipolar Brush Cell (P2–12), filopodial Brush (P12–16), intermediate Brush (P16–21), and dendriolar Brush (P21–28) stages. Electron microscopic measurements of individual mossy fiber-Unipolar Brush Cell and mossy fiber-granule Cell synaptic junctions were made at P12, 16, 21, and 28. While the average length of mossy fiber-Unipolar Brush Cell synapses increased during development, that of mossy fiber-granule Cell synapses decreased. Comparisons of the lengths of mossy fiber-Unipolar Brush Cell and mossy fiber-granule Cell synapses demonstrated that mossy fiber-Unipolar Brush Cell synapses were longer on average than mossy fiber-granule Cell synapses for all ages. Frequency distribution histograms also showed that the percentage of mossy fiber-Unipolar Brush Cell synapses longer than 0.5 μm was lower in the pooled P12–P16 groups than in the pooled P21–P28 groups (8 versus 20%). In contrast, mossy fiber-granule Cell synapses longer than 0.5 μm were a small minority at P12, 16, and 21, and occurred rarely at P28. The present study indicates that mossy fiber-Unipolar Brush Cell synapses increase in length with the differentiation of the Brush dendrioles, while that of mossy fiber-granule Cell synapses decrease with differentiation of the granule Cell dendritic claws. The finding that mossy fiber-Unipolar Brush Cell synapses were generally longer than mossy fiber-granule Cell synapses may indicate that the properties of the postsynaptic targets play a major role in shaping synaptic appositions within cerebellar glomeruli.
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postsynaptic actin filaments at the giant mossy fiber Unipolar Brush Cell synapse
Synapse, 2000Co-Authors: Maria R. Diño, Enrico MugnainiAbstract:The Unipolar Brush Cell (UBC), a small interneuron occurring at high density in the granular layer of the mammalian vestibulocerebellum, receives a giant glutamatergic synapse from a single mossy fiber (MF) rosette, usually on a Brush of dendritic branchlets. MF stimulation produces a current in the UBC several orders of magnitude greater in duration than at other glutamatergic synapses. We assumed that the cytoskeleton would have a special role in plasticity of the MF-UBC synapse. Neurofilaments and microtubules are enriched in the UBC somatodendritic compartment but are conspicuously absent in close proximity to the giant synapse, where standard electron microscopy reveals a granulo-flocculent material. Because osmium tetroxide fixation during sample preparation for standard electron microscopy destabilizes actin filaments, we hypothesized that this subsynaptic granulo-flocculent material is actin-based. After actin stabilization, we observed prominent, but loosely organized, bundles of microfilaments at the subsynaptic region of the MF-UBC synapse that linked the postsynaptic density with the cytoskeletal core of the dendritic branchlets. Confocal fluorescence microscopy and pre- and postembedding immunogold labeling with phalloidin and actin antibodies showed that these microfilaments consist of f-actin and contain little β-actin. This extraordinary postsynaptic actin apparatus is ideally situated to form a dynamic framework for glutamate receptors and other postsynaptic molecules, and to mediate activity-dependent plastic rearrangements of the giant synapse. Synapse 38:499–510, 2000. © 2000 Wiley-Liss, Inc.
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Unipolar Brush Cell a potential feedforward excitatory interneuron of the cerebellum
Neuroscience, 2000Co-Authors: Maria R. Diño, R J Schuerger, N T Slater, Enrico MugnainiAbstract:Abstract Unipolar Brush Cells are a class of interneurons in the granular layer of the mammalian cerebellum that receives excitatory mossy fiber synaptic input in the form of a giant glutamatergic synapse. Previously, it was shown that the Unipolar Brush Cell axon branches within the granular layer, giving rise to large terminals. Single mossy fiber stimuli evoke a prolonged burst of firing in Unipolar Brush Cells, which would be distributed to postsynaptic targets within the granular layer. Knowledge of the ultrastructure of the Unipolar Brush Cell terminals and of the Cellular identity of its postsynaptic targets is required to understand how Unipolar Brush Cells contribute to information processing in the cerebellar circuit. To investigate the Unipolar Brush Cell axon and its targets, Unipolar Brush Cells were patch-clamped in fresh parasagittal slices from rat cerebellar vermis with electrodes filled with Lucifer Yellow and Biocytin, and examined by confocal fluorescence and electron microscopy. Biocytin was localized with diaminobenzidine chromogen or gold-conjugated, silver-intensified avidin. Light microscopic examination revealed a single thin axon emanating from the Unipolar Brush Cell soma that gave rise to 2–3 axon collaterals terminating in mossy fiber-like rosettes in the granular layer, typically within a few hundred μm of the soma. In some cases, axon collaterals crossed the white matter within the same folium before terminating in the adjacent granular layer. Electron microscopic examination of serial ultrathin sections revealed that proximal Unipolar Brush Cell axons and axon collaterals were unmyelinated and devoid of synaptic contacts. However, the rosette-shaped enlargements of each collateral formed the central component of glomeruli where they were surrounded by dendrites of granule Cells and/or other Unipolar Brush Cells, with which they formed asymmetric synaptic contacts. A long-latency repetitive burst of polysynaptic activity was observed in granule Cells in this cerebellar region following white matter stimulation. The Unipolar Brush Cell axons, therefore, form a system of cortex-intrinsic mossy fibers. The results indicate that synaptic excitation of Unipolar Brush Cells by mossy fibers will drive a large population of granule Cells, and thus will contribute a powerful form of distributed excitation within the basic circuit of the cerebellar cortex.
Laurence O. Trussell - One of the best experts on this subject based on the ideXlab platform.
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Selective targeting of Unipolar Brush Cell subtypes by cerebellar mossy fibers.
eLife, 2019Co-Authors: Timothy S. Balmer, Laurence O. TrussellAbstract:While out jogging, you have no trouble keeping your eyes fixed on objects in the distance even though your head and eyes are moving with every step. Humans owe this stability of the visual world partly to a region of the brain called the vestibular cerebellum. From its position underneath the rest of the brain, the vestibular cerebellum detects head motion and then triggers compensatory movements to stabilize the head, body and eyes. The vestibular cerebellum receives sensory input from the body via direct and indirect routes. The direct input comes from five structures within the inner ear, each of which detects movement of the head in one particular direction. The indirect input travels to the cerebellum via the brainstem, which connects the brain with the spinal cord. The indirect input contains information on head movements in multiple directions combined with input from other senses such as vision. By studying the mouse brain, Balmer and Trussell have now mapped the direct and indirect circuits that carry sensory information to the vestibular cerebellum. Both types of input activate Cells within the vestibular cerebellum called Unipolar Brush Cells (UBCs). There are two types of UBCs: ON and OFF. Direct sensory input from the inner ear activates only ON UBCs. These Cells respond to the arrival of sensory input by increasing their activity. Indirect input from the brainstem activates both ON UBCs and OFF UBCs. The latter respond to the input by decreasing their activity. The vestibular cerebellum thus processes direct and indirect inputs via segregated pathways containing different types of UBCs. The next step in understanding how the cerebellum maintains a stable visual world is to identify the circuitry beyond the UBCs. Understanding these circuits will ultimately provide insights into balance disorders, such as vertigo.
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Selective targeting of Unipolar Brush Cell subtypes by cerebellar mossy fibers
2019Co-Authors: Timothy S. Balmer, Laurence O. TrussellAbstract:Abstract In vestibular cerebellum, primary afferents carry signals from single vestibular end organs, whereas secondary afferents from vestibular nucleus carry integrated signals. Selective targeting of distinct mossy fibers to postsynaptic Cells determines how the cerebellum processes vestibular signals. We focused on vestibular projections to ON and OFF classes of Unipolar Brush Cells (UBCs), which transform single mossy fiber signals into long-lasting excitation or inhibition respectively, and impact the activity of ensembles of granule Cells. To determine whether these contacts are indeed selective, connectivity was traced back from UBC to specific ganglion Cell, hair Cell and vestibular organ subtypes. We show that a specialized subset of primary afferents contacts ON UBCs, but not OFF UBCs, while secondary afferents contact both subtypes. Striking anatomical differences were observed between primary and secondary afferents, their synapses, and the UBCs they contact. Thus, each class of UBC functions to transform specific signals through distinct anatomical pathways.
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Slow AMPAR Synaptic Transmission Is Determined by Stargazin and Glutamate Transporters
Neuron, 2017Co-Authors: Timothy S. Balmer, Gabriel E. Romero, Laurence O. TrussellAbstract:AMPARs mediate the briefest synaptic currents in the brain by virtue of their rapid gating kinetics. However, at the mossy fiber-to-Unipolar Brush Cell synapse in the cerebellum, AMPAR-mediated EPSCs last for hundreds of milliseconds, and it has been proposed that this time course reflects slow diffusion from a complex synaptic space. We show that upon release of glutamate, synaptic AMPARs were desensitized by transmitter by >90%. As glutamate levels subsequently fell, recovery of transmission occurred due to the presence of the AMPAR accessory protein stargazin that enhances the AMPAR response to low levels of transmitter. This gradual increase in receptor activity following desensitization accounted for the majority of synaptic transmission at this synapse. Moreover, the amplitude, duration, and shape of the synaptic response was tightly controlled by plasma membrane glutamate transporters, indicating that clearance of synaptic glutamate during the slow EPSC is dictated by an uptake process.
Dick Jaarsma - One of the best experts on this subject based on the ideXlab platform.
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Chapter 8 The Unipolar Brush Cells of the mammalian cerebellum and cochlear nucleus: cytology and microcircuitry
Progress in brain research, 1997Co-Authors: Enrico Mugnaini, Maria R. Di˜o, Dick JaarsmaAbstract:Publisher Summary The Unipolar Brush Cell (UBC) is a novel type of small neuron that is characterized by sets of morphological and chemical phenotypes. UBCs occur in the granular layer of the mammalian cerebellar cortex, particularly in folia of the vestibulocerebellum and in the granule Cell domains of the dorsal cochlear nucleus. The UBC is characterized by a single dendrite that terminates with a Brush-like tip of dendrioles. The dendrioles represent the main synaptic apparatus of the UBC and articulate tightly with a single mossy fiber rosette forming a glomerular array characterized by an extraordinarily extensive synaptic contact. Electron microscopic and electrophysiological observations indicate that the unusual synaptic ultrastructure may produce entrapment of neurotransmitter in the synaptic cleft. The UBC Brush occupies a glomerulus where granule Cell dendrites are intermixed with the UBC dendrioles, both of which receive synapses from the same mossy fiber rosette and portions of the Golgi axonal plexus.
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cerebellar choline acetyltransferase positive mossy fibres and their granule and Unipolar Brush Cell targets a model for central cholinergic nicotinic neurotransmission
Journal of Neurocytology, 1996Co-Authors: Maria R. Diño, Dick Jaarsma, C Cozzari, Enrico MugnainiAbstract:A subset of cerebellar mossy fibres is rich in choline acetyltransferase, the rate-limiting enzyme for the synthesis of acetylcholine. These choline acetyltransferase-positive mossy fibres are concentrated in the vestibulocerebellum and originate predominantly from the medial vestibular nucleus. The granular layer of the vestibulocerebellum is also enriched in Unipolar Brush Cells, an unusual type of small neuron that form giant synapses with mossy fibres. In this immunocytochemical light and electron microscopic study, we explored whether choline acetyltransferase-positive mossy fibres innervate Unipolar Brush Cells of the rat cerebellum. We utilized monoclonal antibodies to rat choline acetyltransferase of proven specificity, and immunoperoxidase procedures with 3,3'-diaminobenzidine tetrahydrochloride as the chromogen. A high density of choline acetyltransferase-positive fibres occurred in the nodulus and ventral uvula, where they showed an uneven, zonal distribution. Immunostained mossy fibre rosettes contained high densities of round synaptic vesicles and mitochondria. They formed asymmetric synaptic junctions with dendritic profiles of both granule Cells and Unipolar Brush Cells. The synaptic contacts between choline acetyltransferase-immunoreactive mossy fibres and Unipolar Brush Cells were very extensive, and did not differ from synapses of choline acetyltransferase-negative mossy fibres with Unipolar Brush Cells. Analysis of a total area of 1.25 mm2 of the nodulus from three rats revealed that 14.2% of choline acetyltransferase-immunoreactive mossy fibre rosettes formed synapses with Unipolar Brush Cells profiles. Choline acetyltransferase-positive rosettes accounted for 21.7% of the rosettes forming synapses with Unipolar Brush Cells. Thus, the present data demonstrate that Unipolar Brush Cells are innervated by a heterogeneous population of mossy fibres, and that some Unipolar Brush Cells receive cholinergic synaptic input from the medial vestibular nucleus. The ultrastructure of these synapses is compatible with the possibility that choline acetyltransferase-positive mossy fibres co-release acetylcholine and glutamate. As the granular layer of the vestibulocerebellum contains nicotinic binding sites, the choline acetyltransferase-positive mossy fibres may be a model for studying nicotinic neurotransmission in the CNS.
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Glutamate receptor subunits at mossy fiber‐Unipolar Brush Cell synapses: Light and electron microscopic immunocytochemical study in cerebellar cortex of rat and cat
The Journal of comparative neurology, 1995Co-Authors: Dick Jaarsma, Robert J. Wenthold, Enrico MugnainiAbstract:The present study provides a survey of the immunolocalization of ionotropic glutamate receptor subunits throughout the rat and cat cerebellar cortex, with emphasis on the Unipolar Brush Cell (UBC), a hitherto neglected cerebellar Cell that is densely concentrated in the granular layer of the vestibulocerebellum and that forms giant synapses with mossy fibers. An array of nine previously characterized antibodies has been used, each of which stained a characteristic profile of cerebellar Cells. The UBCs of both rat and cat were strongly immunostained by an antibody against the α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA) receptor subunits, GluR2 and GluR3; were moderately immunostained by a monoclonal antibody to kainate receptor subunits, GluR5/6/7; were weakly immunostained by antibodies to NR1 subunits; and were not stained by antibodies to GluR1, GluR4, GluR6/7, KA-2, and NR2A/B. Postsynaptic densities of the giant mossy fiber-UBC synapses were GluR2/3, GluR5/6/7, and NR1 immunoreactive. The other cerebellar neurons were all immunolabeled to some extent with the GluR2/3 and NR1 antibodies. In addition, Purkinje Cells were immunopositive for GluRl and GluR5/6/7; granule Cells were immunopositive for GluR5/6/7, GluR6/7, KA-2, and NR2A/B. The Golgi-Bergmann glia was densely stained by GluRl and GluR4 antibodies, whereas astrocytes of the granular layer were stained by the GluR4 antiserum. Data provided herein may guide further electrophysiological and pharmacological studies of cerebellar Cells in general and the UBCs in particular. © 1995 Wiley-Liss, Inc.
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glutamate receptor subunits at mossy fiber Unipolar Brush Cell synapses light and electron microscopic immunocytochemical study in cerebellar cortex of rat and cat
The Journal of Comparative Neurology, 1995Co-Authors: Dick Jaarsma, Robert J. Wenthold, Enrico MugnainiAbstract:The present study provides a survey of the immunolocalization of ionotropic glutamate receptor subunits throughout the rat and cat cerebellar cortex, with emphasis on the Unipolar Brush Cell (UBC), a hitherto neglected cerebellar Cell that is densely concentrated in the granular layer of the vestibulocerebellum and that forms giant synapses with mossy fibers. An array of nine previously characterized antibodies has been used, each of which stained a characteristic profile of cerebellar Cells. The UBCs of both rat and cat were strongly immunostained by an antibody against the α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA) receptor subunits, GluR2 and GluR3; were moderately immunostained by a monoclonal antibody to kainate receptor subunits, GluR5/6/7; were weakly immunostained by antibodies to NR1 subunits; and were not stained by antibodies to GluR1, GluR4, GluR6/7, KA-2, and NR2A/B. Postsynaptic densities of the giant mossy fiber-UBC synapses were GluR2/3, GluR5/6/7, and NR1 immunoreactive. The other cerebellar neurons were all immunolabeled to some extent with the GluR2/3 and NR1 antibodies. In addition, Purkinje Cells were immunopositive for GluRl and GluR5/6/7; granule Cells were immunopositive for GluR5/6/7, GluR6/7, KA-2, and NR2A/B. The Golgi-Bergmann glia was densely stained by GluRl and GluR4 antibodies, whereas astrocytes of the granular layer were stained by the GluR4 antiserum. Data provided herein may guide further electrophysiological and pharmacological studies of cerebellar Cells in general and the UBCs in particular. © 1995 Wiley-Liss, Inc.
John I. Simpson - One of the best experts on this subject based on the ideXlab platform.
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Visuo-Vestibular Information Processing by Unipolar Brush Cells in the Rabbit Flocculus
The Cerebellum, 2015Co-Authors: Robert A. Hensbroek, Boeke J. Beugen, Jun Maruta, Tom J H Ruigrok, John I. SimpsonAbstract:The Unipolar Brush Cell (UBC) is a glutamatergic granular layer interneuron that is predominantly located in the vestibulocerebellum and parts of the vermis. In rat and rabbit, we previously found using juxtaCellular labeling combined with spontaneous activity recording that Cells with highly regular spontaneous activity belong to the UBC category. Making use of this signature, we recorded from floccular UBCs in both anesthetized and awake rabbits while delivering visuo-vestibular stimulation by using sigmoidal rotation of the whole animal. In the anesthetized rabbit, the activity of the presumed UBC units displayed a wide variety of modulation profiles that could be related to aspects of head velocity or acceleration. These modulation profiles could also be found in the awake rabbit where, in addition, they could also carry an eye position signal. Furthermore, units in the awake rabbit could demonstrate rather long response latencies of up to 0.5 s. We suggest that the UBCs recorded in this study mostly belong to the type I UBC category (calretinin-positive) and that they can play diverse roles in floccular visuo-vestibular information processing, such as transformation of velocity-related signals to acceleration-related signals.
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REVIEW Visuo-Vestibular Information Processing by Unipolar Brush Cells in the Rabbit Flocculus
2015Co-Authors: John I. SimpsonAbstract:# The Author(s) 2015. This article is published with open access at Springerlink.com Abstract The Unipolar Brush Cell (UBC) is a glutamatergic granular layer interneuron that is predominantly located in the vestibulocerebellum and parts of the vermis. In rat and rabbit, we previously found using juxtaCellular labeling combined with spontaneous activity recording that Cells with highly reg-ular spontaneous activity belong to the UBC category.Making use of this signature, we recorded from floccular UBCs in both anesthetized and awake rabbits while delivering visuo-vestibular stimulation by using sigmoidal rotation of the whole animal. In the anesthetized rabbit, the activity of the presumed UBC units displayed a wide variety of modulation profiles that could be related to aspects of head velocity or acceleration. These modulation profiles could also be found in the awake rabbit where, in addition, they could also carry an eye position signal. Furthermore, units in the awake rabbit could demonstrate rather long response latencies of up to 0.5 s. We suggest that the UBCs recorded in this study mostly belong to the type I UBC category (calretinin-positive) and that they can play diverse roles in floccular visuo-vestibular information processing, such as transformation of velocity-related signals to acceleration-related signals
