Climbing fiber-triggered metabotropic slow potentials enhance dendritic calcium transients and simple spike firing in cerebellar Purkinje cells

Yuan, Qi; Qiu, De-Lai; Weber, John T.; Hansel, Christian; Knöpfel, Thomas

doi:10.1016/j.mcn.2007.05.004

Cited by 21 publications

(21 citation statements)

References 35 publications

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“…It is conceivable that ethanol targets TRPC channels (or another protein that is attached to the mGluR1/TRPC complex), rather than mGluR1 itself. The consequences for LTD induction might well be the same because slow mGluR1-activated potentials can enhance dendritic calcium transients (Yuan et al 2007) and, by doing so, might facilitate LTD induction (Coesmans et al 2004). It certainly is conceivable that ethanol affects a signaling factor downstream of mGluR1 receptor activation.…”

Section: Discussionmentioning

confidence: 99%

“…These receptors are expressed in Purkinje cells during development; only recently, functional NMDA receptors have been described at climbing fiber (CF) synapses onto mature Purkinje cells (Piochon et al 2007;Renzi et al 2007). Ethanol indeed inhibits the late phase of CF-evoked complex spikes, but this downregulation is due to an inhibition of mGluR1 receptors (Carta et al 2006), which can mediate slow, metabotropic currents (mGluR1-excitatory postsynaptic currents [EPSCs]) on CF activation (Dzubay and Otis 2002;Yuan et al 2007). Early complex spike components and CF-EPSCs remained unaffected by ethanol application (Carta et al 2006), suggesting that ethanol does not modulate ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor function in Purkinje cells.…”

Section: Introductionmentioning

confidence: 99%

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Alcohol Impairs Long-Term Depression at the Cerebellar Parallel Fiber–Purkinje Cell Synapse

Belmeguenaï

Botta²,

Weber³

et al. 2008

Journal of Neurophysiology

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Acute alcohol consumption causes deficits in motor coordination and gait, suggesting an involvement of cerebellar circuits, which play a role in the fine adjustment of movements and in motor learning. It has previously been shown that ethanol modulates inhibitory transmission in the cerebellum and affects synaptic transmission and plasticity at excitatory climbing fiber (CF) to Purkinje cell synapses. However, it has not been examined thus far how acute ethanol application affects long-term depression (LTD) and long-term potentiation (LTP) at excitatory parallel fiber (PF) to Purkinje cell synapses, which are assumed to mediate forms of cerebellar motor learning. To examine ethanol effects on PF synaptic transmission and plasticity, we performed whole cell patch-clamp recordings from Purkinje cells in rat cerebellar slices. We found that ethanol (50 mM) selectively blocked PF-LTD induction, whereas it did not change the amplitude of excitatory postsynaptic currents at PF synapses. In contrast, ethanol application reduced voltage-gated calcium currents and type 1 metabotropic glutamate receptor (mGluR1)-dependent responses in Purkinje cells, both of which are involved in PF-LTD induction. The selectivity of these effects is emphasized by the observation that ethanol did not impair PF-LTP and that PF-LTP could readily be induced in the presence of the group I mGluR antagonist AIDA or the mGluR1a antagonist LY367385. Taken together, these findings identify calcium currents and mGluR1-dependent signaling pathways as potential ethanol targets and suggest that an ethanol-induced blockade of PF-LTD could contribute to the motor coordination deficits resulting from alcohol consumption.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alcohol Impairs Long-Term Depression at the Cerebellar Parallel Fiber–Purkinje Cell Synapse

Belmeguenaï

Botta²,

Weber³

et al. 2008

Journal of Neurophysiology

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“…We used kynurenic acid to block the response for the MRI experiments as it remains potent in stock solution form for longer periods of time than the mGluR blocker (LY341495). Kynurenate as well as other antagonists of excitatory amino acid receptors are known to block the mGluR-mediated evoked response of the Purkinje cells (Larson-Prior and Slater, 1989; Larson-Prior et al, 1995; Yuan et al, 2007). The solution was exchanged outside the scanner without disturbing the preparation.…”

Section: Methodsmentioning

confidence: 99%

Direct neural current imaging in an intact cerebellum with magnetic resonance imaging

et al. 2016

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The ability to detect neuronal currents with high spatiotemporal resolution using magnetic resonance imaging (MRI) is important for studying human brain function in both health and disease. While significant progress has been made, we still lack evidence showing that it is possible to measure an MR signal time-locked to neuronal currents with a temporal waveform matching concurrently recorded local field potentials (LFPs). Also lacking is evidence that such MR data can be used to image current distribution in active tissue. Since these two results are lacking even in vitro, we obtained these data in an intact isolated whole cerebellum of turtle during slow neuronal activity mediated by metabotropic glutamate receptors using a gradient-echo EPI sequence (TR = 100 ms) at 4.7 T. Our results show that it is possible (1) to reliably detect an MR phase shift time course matching that of the concurrently measured LFP evoked by stimulation of a cerebellar peduncle, (2) to detect the signal in single voxels of 0.1 mm3, (3) to determine the spatial phase map matching the magnetic field distribution predicted by the LFP map, (4) to estimate the distribution of neuronal current in the active tissue from a group-average phase map, and (5) to provide a quantitatively accurate theoretical account of the measured phase shifts. The peak values of the detected MR phase shifts were 0.27–0.37°, corresponding to local magnetic field changes of 0.67–0.93 nT (for TE = 26 ms). Our work provides an empirical basis for future extensions to in vivo imaging of neuronal currents.

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“…4), whereas Ca 2ϩ released from internal stores can relay the effect of mGluR1 activation to the dendritic shafts. Although the current paper focuses on the physiological implications of T-type potentiation at PF-PC synapses within PC spines, the potentiation of T-type currents at CF-PC synapses in the proximal dendrites could have significant effects on PC excitability, such as generating mGluR1-mediated dendritic Ca 2ϩ transients and altering firing thresholds (Yuan et al, 2007). These possibilities are currently under investigation.…”

Section: Mglur1 Potentiates T-type Camentioning

confidence: 99%

Functional Coupling between mGluR1 and Ca_v3.1 T-Type Calcium Channels Contributes to Parallel Fiber-Induced Fast Calcium Signaling within Purkinje Cell Dendritic Spines

Hildebrand¹,

Isope²,

Miyazaki³

et al. 2009

J. Neurosci.

131

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T-type voltage-gated calcium channels are expressed in the dendrites of many neurons, although their functional interactions with postsynaptic receptors and contributions to synaptic signaling are not well understood. We combine electrophysiological and ultrafast two-photon calcium imaging to demonstrate that mGluR1 activation potentiates cerebellar Purkinje cell Ca v 3.1 T-type currents via a G-protein-and tyrosine-phosphatase-dependent pathway. Immunohistochemical and electron microscopic investigations on wild-type and Ca v 3.1 gene knock-out animals show that Ca v 3.1 T-type channels are preferentially expressed in Purkinje cell dendritic spines and colocalize with mGluR1s. We further demonstrate that parallel fiber stimulation induces fast subthreshold calcium signaling in dendritic spines and that the synaptic Ca v 3.1-mediated calcium transients are potentiated by mGluR1 selectively during bursts of excitatory parallel fiber inputs. Our data identify a new fast calcium signaling pathway in Purkinje cell dendritic spines triggered by short burst of parallel fiber inputs and mediated by T-type calcium channels and mGluR1s.

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Climbing fiber-triggered metabotropic slow potentials enhance dendritic calcium transients and simple spike firing in cerebellar Purkinje cells

Cited by 21 publications

References 35 publications

Alcohol Impairs Long-Term Depression at the Cerebellar Parallel Fiber–Purkinje Cell Synapse

Alcohol Impairs Long-Term Depression at the Cerebellar Parallel Fiber–Purkinje Cell Synapse

Direct neural current imaging in an intact cerebellum with magnetic resonance imaging

Functional Coupling between mGluR1 and Ca_v3.1 T-Type Calcium Channels Contributes to Parallel Fiber-Induced Fast Calcium Signaling within Purkinje Cell Dendritic Spines

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Climbing fiber-triggered metabotropic slow potentials enhance dendritic calcium transients and simple spike firing in cerebellar Purkinje cells

Cited by 21 publications

References 35 publications

Alcohol Impairs Long-Term Depression at the Cerebellar Parallel Fiber–Purkinje Cell Synapse

Alcohol Impairs Long-Term Depression at the Cerebellar Parallel Fiber–Purkinje Cell Synapse

Direct neural current imaging in an intact cerebellum with magnetic resonance imaging

Functional Coupling between mGluR1 and Cav3.1 T-Type Calcium Channels Contributes to Parallel Fiber-Induced Fast Calcium Signaling within Purkinje Cell Dendritic Spines

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Functional Coupling between mGluR1 and Ca_v3.1 T-Type Calcium Channels Contributes to Parallel Fiber-Induced Fast Calcium Signaling within Purkinje Cell Dendritic Spines