Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit

Zampini, Valeria; Liu, Jian K.; Diana, Marco A.; Maldonado, Paloma P.; Brunel, Nicolas; Dieudonné, Stéphane

doi:10.7554/elife.15872

Cited by 53 publications

(97 citation statements)

References 81 publications

(148 reference statements)

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“…EPSCs in stg UBCs showed both fast and slow components upon train stimulation, as in wt UBCs (Fig 4A, B). Scatter plots of peak amplitude of fast EPSCs vs slow EPSCs from different UBCs were positively correlated (R 2 =0.163; p=0.0027, n=53), presumably as synapses varied in their size, quantal content, and numbers of AMPARs (Zampini et al, 2016). However, when plotted for each mouse line, stg slow currents appeared to be smaller than in wt over a similar range of fast EPSCs (Fig 4A, B, red vs black traces and points).…”

Section: Resultsmentioning

confidence: 99%

“…The fast-then-slow EPSC sequence that is characteristic of UBCs was evoked by a 100-Hz, 10-stimulus train in mouse cerebellar brain slices (STAR Methods, Fig 1A–B) (Borges-Merjane and Trussell, 2015; van Dorp and de Zeeuw, 2014; Rossi et al, 1995; Zampini et al, 2016). A complete block of the EPSC by GYKI-53655 (GYKI) (75 μM) confirmed that the slow currents were AMPAR-mediated (Fig 1B).…”

Section: Resultsmentioning

confidence: 99%

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Slow AMPAR Synaptic Transmission Is Determined by Stargazin and Glutamate Transporters

Balmer

Romero

et al. 2017

Neuron

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Summary 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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Slow AMPAR Synaptic Transmission Is Determined by Stargazin and Glutamate Transporters

Balmer

Romero

et al. 2017

Neuron

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“…We found that the low-frequency (<2 Hz) component of acceleration during free movements mainly contains gravitational information. The granular layer of the caudal vermis contains a high amount of unipolar brush cells (excitatory interneurons intercalated between mossy fibers and granule cells) which may smooth otolithic signals over hundreds of milliseconds (van Dorp & De Zeeuw, 2014; Borges-Merjane & Trussell, 2015; Zampini et al, 2016) and thus provide a proxy of gravitational signals to granule cells. Granule cells receiving convergent inputs carrying gravitational and rotational information could then operate as coincidence detectors (Chadderton et al, 2004; Chabrol et al, 2015) and signal the occurrence of specific combinations of rotation and head tilt to Purkinje cells.…”

Section: Discussionmentioning

confidence: 99%

Cerebellar re-encoding of self-generated head movements

Dugué

Tihy

Gourévitch

et al. 2017

Preprint

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Head movements are primarily sensed in a reference frame tied to the head, yet they 2 are used to calculate self-orientation relative to the world. This requires to re-encode head kinematic signals into a reference frame anchored to earth-centered landmarks 4 such as gravity, through computations whose neuronal substrate remains to be determined. Here, we studied the encoding of self-generated head movements in the 6 caudal cerebellar vermis, an area essential for graviceptive functions. We found that, contrarily to peripheral vestibular inputs, most Purkinje cells exhibited a mixed sen-8 sitivity to head rotational and gravitational information and were differentially modulated by active and passive movements. In a subpopulation of cells, this mixed sen-10 sitivity underlay a tuning to rotations about an axis defined relative to gravity. Therefore, we show that the caudal vermis hosts a re-encoded, gravitationally-polarized 12 representation of self-generated head kinematics.

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“…For example, the activity patterns and learning mechanisms of different cerebellar modules may be dominated by Purkinje cells with different intrinsic electrophysiological and biochemical properties (Cerminara et al, ; De Zeeuw & Ten Brinke, ; Zhou et al, ;). In addition, the flocculus and nodulus of the vestibulocerebellum, which are involved in compensatory eye and body movements (Ito, ; Lisberger, ; Schonewille et al, ; Voogd, Schraa‐Tam, van der Geest, & De Zeeuw, ) show a marked enrichment of unipolar brush cells (UBCs), an excitatory granular layer interneuron, which can prolong the excitatory drive of the mossy fiber system (Gao et al, ; Sekerkova, Watanabe, Martina, & Mugnaini, ; van Dorp & De Zeeuw, ; Zampini et al, ). Furthermore, there is evidence for heterogeneity of inhibitory granule cell layer interneurons across distinct lobules (Ankri et al, ; Eyre & Nusser, ; Neki et al, ; Simat, Parpan, & Fritschy, ;).…”

Section: Introductionmentioning

confidence: 99%

The basal interstitial nucleus (BIN) of the cerebellum provides diffuse ascending inhibitory input to the floccular granule cell layer

Jaarsma

Blot

et al. 2018

J of Comparative Neurology

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The basal interstitial nucleus (BIN) in the white matter of the vestibulocerebellum has been defined more than three decades ago, but has since been largely ignored. It is still unclear which neurotransmitters are being used by BIN neurons, how these neurons are connected to the rest of the brain and what their activity patterns look like. Here, we studied BIN neurons in a range of mammals, including macaque, human, rat, mouse, rabbit, and ferret, using tracing, immunohistological and electrophysiological approaches. We show that BIN neurons are GABAergic and glycinergic, that in primates they also express the marker for cholinergic neurons choline acetyl transferase (ChAT), that they project with beaded fibers to the glomeruli in the granular layer of the ipsilateral floccular complex, and that they are driven by excitation from the ipsilateral and contralateral medio-dorsal medullary gigantocellular reticular formation. Systematic analysis of codistribution of the inhibitory synapse marker VIAAT, BIN axons, and Golgi cell marker mGluR2 indicate that BIN axon terminals complement Golgi cell axon terminals in glomeruli, accounting for a considerable proportion ( > 20%) of the inhibitory terminals in the granule cell layer of the floccular complex. Together, these data show that BIN neurons represent a novel and relevant inhibitory input to the part of the vestibulocerebellum that controls compensatory and smooth pursuit eye movements.

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Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit

Cited by 53 publications

References 81 publications

Slow AMPAR Synaptic Transmission Is Determined by Stargazin and Glutamate Transporters

Slow AMPAR Synaptic Transmission Is Determined by Stargazin and Glutamate Transporters

Cerebellar re-encoding of self-generated head movements

The basal interstitial nucleus (BIN) of the cerebellum provides diffuse ascending inhibitory input to the floccular granule cell layer

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