Unipolar brush cell axons form a large system of intrinsic mossy fibers in the postnatal vestibulocerebellum

Nunzi, Maria Grazia; Mugnaini, Enrico

doi:10.1002/(sici)1096-9861(20000619)422:1<55::aid-cne4>3.0.co;2-9

Cited by 86 publications

(60 citation statements)

References 40 publications

(51 reference statements)

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“…UBCs and GCs are both classes of feedforward excitatory interneurons in the cerebellar granular layer that receive input both from extrinsic mossy fibers (Eccles et al 1967;Ito 1984;Llinás 1984;Mugnaini 1972;Palay and Chan-Palay 1974) and intrinsic mossy fibers that arise from a subset of first-order UBCs (Diño et al 2000;Nunzi and Mugnaini 2000;. A small number of first-order UBCs receive extrinsic mossy fiber input and their axons form a network within the granular layer whose terminals form miniature glomeruli which drive populations of second-order UBCs and GCs.…”

Section: Functional Significancementioning

confidence: 99%

NMDA Receptor-Mediated Currents in Rat Cerebellar Granule and Unipolar Brush Cells

Billups

Liu

Birnstiel

et al. 2002

Journal of Neurophysiology

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verse Slater. NMDA receptor-mediated currents in rat cerebellar granule and unipolar brush cells. J Neurophysiol 87: 1948 -1959, 2002; 10.1152/jn.00599.2001. The properties of N-methyl-D-aspartate (NMDA) receptor-mediated currents at the giant cerebellar mossyfiber unipolar brush cell (UBC) synapse were compared with those of adjacent granule cells using patch-clamp recording methods in thin slices of rat cerebellar nodulus. In UBCs, NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) decayed as a single exponential whose time constant was independent of membrane potential. The EPSC was reduced in all cells by the NR1/NR2B-selective antagonist ifenprodil, and the Zn 2ϩ chelator N,N,NЈ,NЈ-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) produced a transient potentiation in 50% of cells. In contrast, the NMDA EPSC in granule cells decayed as a double exponential that dramatically switched to a slower rate at positive membrane potentials. The synaptic response in some granule cells also displayed a late second peak at positive potentials, and in others, activation of mossy fibers produced repetitive trains of EPSCs indicating they may be postsynaptic to the UBC network. Single-channel recordings of outside-out somatic patches from UBCs in magnesium-free solution revealed only high-conductance (50 pS) channels whose open time was increased with depolarization, but the opening frequency was decreased to yield a low (p o ϭ 0.0298), voltage-independent opening probability. Lowering extracellular calcium (2.5-0.25 mM) had no effects on channel gating, although an increase of single-channel conductance was observed at lower calcium concentrations. Taken together, the data support the notion that the NMDA receptor in UBCs may comprise both NR1/ NR2A and NR1/NR2B receptors. Furthermore, the properties of the EPSC in these two classes of feedforward glutamatergic interneurons display fundamental differences that may relate to their roles in synaptic integration.

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Section: Functional Significancementioning

confidence: 99%

NMDA Receptor-Mediated Currents in Rat Cerebellar Granule and Unipolar Brush Cells

Billups

Liu

Birnstiel

et al. 2002

Journal of Neurophysiology

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“…UBCs form a class of glutamatergic interneurons (Nunzi et al, 2001) morphologically characterized by a single dendrite originating from the soma and terminating in a brush-like structure composed of several dendrioles. A key region for synaptic integration, the brush receives a single giant excitatory synapse, which is formed either by an extrinsic vestibular fiber or by the axon of another UBC (Jaarsma et al, 1995;Mugnaini et al, 1997;Nunzi et al, 2000Nunzi et al, , 2001. The presynaptic element of this synapse shows the typical ultrastructure of mossy fiber (mf) terminals but forms an exceptionally extended synaptic contact that can entrap glutamate for several hundred milliseconds, thus enabling unusually long excitatory responses (Rossi et al, 1995;Kinney et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…UBCs provide a strong feed-forward excitatory input onto other UBCs and granule cells (Nunzi et al, 2000(Nunzi et al, , 2001 via axonal mf-like terminals and possibly onto granule cells via dendrodendritic synapses (Mugnaini et al, 1997). Several arguments suggest that UBCs are important elements in the vestibulocerebellar circuitry.…”

Section: Introductionmentioning

confidence: 99%

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T-Type and L-Type Ca²⁺Conductances Define and Encode the Bimodal Firing Pattern of Vestibulocerebellar Unipolar Brush Cells

Diana¹,

Otsu²,

Maton³

et al. 2007

J. Neurosci.

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Cerebellar unipolar brush cells (UBCs) are glutamatergic interneurons that receive direct input from vestibular afferents in the form of a unique excitatory synapse on their dendritic brush. UBCs constitute independent relay lines for vestibular signals, and their inherent properties most likely determine how vestibular activity is encoded by the cerebellar cortex. We now demonstrate that UBCs are bimodal cells; they can either fire high-frequency bursts of action potentials when stimulated from hyperpolarized potentials or discharge tonically during sustained depolarizations. The two functional states can be triggered by physiological-like activity of the excitatory input and are encoded by distinct Ca 2ϩ -signaling systems. By combining complementary strategies, consisting of molecular and electrophysiological analysis and of ultrafast acousto-optical deflector-based two-photon imaging, we unraveled the identity and the subcellular localization of the Ca 2ϩ conductances activating in each mode. Fast inactivating T-type Ca 2ϩ channels produce low-threshold spikes, which trigger the high-frequency bursts and generate powerful Ca 2ϩ transients in the brush and, to a much lesser extent, in the soma. The tonic firing mode is encoded by a signalization system principally composed of L-type channels. Ca 2ϩ influx during tonic firing produces a linear representation of the spike rate of the cell in the form of a widespread and sustained Ca 2ϩ concentration increase and regulates cellular excitability via BK potassium channels. The bimodal firing pattern of UBCs may underlie different coding strategies of the vestibular input by the cerebellum, thus likely increasing the computational power of this structure.

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“…As for external mossy fibers, the terminals on UBC axons form the cores of glomeruli where they contact tens of granule cells and, in some cases, other UBCs. UBCs thus form an intricate network of excitatory feedforward projections within the granular layer, and it has been estimated that in the nodulus at least 50% of mossy fiber terminals arise from UBCs (12). The peculiar specialization of the synapse, in combination with the strategic position in the granular layer network, is likely to allow UBCs to importantly influence cortical information processing (13,14).…”

mentioning

confidence: 99%

Variable timing of synaptic transmission in cerebellar unipolar brush cells

Dorp

Zeeuw

2014

Proc. Natl. Acad. Sci. U.S.A.

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The cerebellum ensures the smooth execution of movements, a task that requires accurate neural signaling on multiple time scales. Computational models of cerebellar timing mechanisms have suggested that temporal information in cerebellum-dependent behavioral tasks is in part computed locally in the cerebellar cortex. These models rely on the local generation of delayed signals spanning hundreds of milliseconds, yet the underlying neural mechanism remains elusive. Here we show that a granular layer interneuron, called the unipolar brush cell, is well suited to represent time intervals in a robust way in the cerebellar cortex. Unipolar brush cells exhibited delayed increases in excitatory synaptic input in response to presynaptic stimulation in mouse cerebellar slices. Depending on the frequency of stimulation, delays extended from zero up to hundreds of milliseconds. Such controllable protraction of delayed currents was the result of an unusual mode of synaptic integration, which was well described by a model of steady-state AMPA receptor activation. This functionality extends the capabilities of the cerebellum for adaptive control of behavior by facilitating appropriate output in a broad temporal window.spreading diversity | neural timing D esensitization of AMPA receptors (AMPARs) can significantly influence synaptic transmission at glutamatergic synapses (1). AMPARs have an affinity to desensitize to concentrations of glutamate in the micromolar range, and desensitization can become nearly complete at saturating concentrations (2, 3). In particular, at calyceal or glomerular synapses, spillover-induced desensitization contributes to short-term depression of AMPARmediated transmission (4, 5). An extreme case of spillover-induced desensitization is believed to mediate synaptic transmission in unipolar brush cells (UBCs) of the cerebellum. UBCs are small glutamatergic granular layer interneurons (typical soma diameter ∼ 10 μm), which in rodents are most abundant in the vestibulo-cerebellum (6). They have a single, bushy dendrite that connects with a mossy fiber terminal in a one-to-one fashion, forming a giant glutamatergic synapse with large area of apposition and many release sites. At most central synapses, the lifetime of neurotransmitter in the cleft is short, limited by rapid diffusional escape to the surrounding medium (7). However, the glomerular structure and extensive synaptic apposition of UBC synapses have been hypothesized to promote prolonged entrapment of glutamate in the synaptic cleft (8, 9).Excitatory postsynaptic currents (EPSCs) recorded from rat UBCs have a classical fast component, mediated by AMPARs, followed by a protracted tail of persistent inward current that can last up to seconds. The slow tail is believed to be due to the prolonged presence of glutamate in the cleft and is mediated by NMDA receptors (NMDARs) or AMPARs, or a combination of both (8). In most UBCs, the biphasic appearance of EPSCs is particularly striking as the slow current first rises to peak in several hundreds of mi...

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Unipolar brush cell axons form a large system of intrinsic mossy fibers in the postnatal vestibulocerebellum

Cited by 86 publications

References 40 publications

NMDA Receptor-Mediated Currents in Rat Cerebellar Granule and Unipolar Brush Cells

NMDA Receptor-Mediated Currents in Rat Cerebellar Granule and Unipolar Brush Cells

T-Type and L-Type Ca²⁺Conductances Define and Encode the Bimodal Firing Pattern of Vestibulocerebellar Unipolar Brush Cells

Variable timing of synaptic transmission in cerebellar unipolar brush cells

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Unipolar brush cell axons form a large system of intrinsic mossy fibers in the postnatal vestibulocerebellum

Cited by 86 publications

References 40 publications

NMDA Receptor-Mediated Currents in Rat Cerebellar Granule and Unipolar Brush Cells

NMDA Receptor-Mediated Currents in Rat Cerebellar Granule and Unipolar Brush Cells

T-Type and L-Type Ca2+Conductances Define and Encode the Bimodal Firing Pattern of Vestibulocerebellar Unipolar Brush Cells

Variable timing of synaptic transmission in cerebellar unipolar brush cells

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T-Type and L-Type Ca²⁺Conductances Define and Encode the Bimodal Firing Pattern of Vestibulocerebellar Unipolar Brush Cells