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Find video protocols related to scientific articles indexed in Pubmed.
mGluR1-mediated excitation of cerebellar GABAergic interneurons requires both G protein-dependent and Src-ERK1/2-dependent signaling pathways.
PLoS ONE
PUBLISHED: 09-02-2014
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Stimulation of type I metabotropic glutamate receptors (mGluR1/5) in several neuronal types induces slow excitatory responses through activation of transient receptor potential canonical (TRPC) channels. GABAergic cerebellar molecular layer interneurons (MLIs) modulate firing patterns of Purkinje cells (PCs), which play a key role in cerebellar information processing. MLIs express mGluR1, and activation of mGluR1 induces an inward current, but its precise intracellular signaling pathways are unknown. We found that mGluR1 activation facilitated spontaneous firing of mouse cerebellar MLIs through an inward current mediated by TRPC1 channels. This mGluR1-mediated inward current depends on both G protein-dependent and -independent pathways. The nonselective protein tyrosine kinase inhibitors genistein and AG490 as well as the selective extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitors PD98059 and SL327 suppressed the mGluR1-mediated current responses. Following G protein blockade, the residual mGluR1-mediated inward current was significantly reduced by the selective Src tyrosine kinase inhibitor PP2. In contrast to cerebellar PCs, GABAB receptor activation in MLIs did not alter the mGluR1-mediated inward current, suggesting that there is no cross-talk between mGluR1 and GABAB receptors in MLIs. Thus, activation of mGluR1 facilitates firing of MLIs through the TRPC1-mediated inward current, which depends on not only G protein-dependent but also Src-ERK1/2-dependent signaling pathways, and consequently depresses the excitability of cerebellar PCs.
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Type 1 inositol trisphosphate receptor regulates cerebellar circuits by maintaining the spine morphology of purkinje cells in adult mice.
J. Neurosci.
PUBLISHED: 07-26-2013
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The structural maintenance of neural circuits is critical for higher brain functions in adulthood. Although several molecules have been identified as regulators for spine maintenance in hippocampal and cortical neurons, it is poorly understood how Purkinje cell (PC) spines are maintained in the mature cerebellum. Here we show that the calcium channel type 1 inositol trisphosphate receptor (IP3R1) in PCs plays a crucial role in controlling the maintenance of parallel fiber (PF)-PC synaptic circuits in the mature cerebellum in vivo. Significantly, adult mice lacking IP3R1 specifically in PCs (L7-Cre;Itpr1(flox/flox)) showed dramatic increase in spine density and spine length of PCs, despite having normal spines during development. In addition, the abnormally rearranged PF-PC synaptic circuits in mature cerebellum caused unexpectedly severe ataxia in adult L7-Cre;Itpr1(flox/flox) mice. Our findings reveal a specific role for IP3R1 in PCs not only as an intracellular mediator of cerebellar synaptic plasticity induction, but also as a critical regulator of PF-PC synaptic circuit maintenance in the mature cerebellum in vivo; this mechanism may underlie motor coordination and learning in adults.
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IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice.
Front Neural Circuits
PUBLISHED: 01-01-2013
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The type 1 inositol 1,4,5- trisphosphate receptor (IP3R1) is a Ca(2+) channel on the endoplasmic reticulum and is a predominant isoform in the brain among the three types of IP3Rs. Mice lacking IP3R1 show seizure-like behavior; however the cellular and neural circuit mechanism by which IP3R1 deletion causes the abnormal movements is unknown. Here, we found that the conditional knockout mice lacking IP3R1 specifically in the cerebellum and brainstem experience dystonia and show that cerebellar Purkinje cell (PC) firing patterns were coupled to specific dystonic movements. Recordings in freely behaving mice revealed epochs of low and high frequency PC complex spikes linked to body extension and rigidity, respectively. Remarkably, dystonic symptoms were independent of the basal ganglia, and could be rescued by inactivation of the cerebellum, inferior olive or in the absence of PCs. These findings implicate IP3R1-dependent PC firing patterns in cerebellum in motor coordination and the expression of dystonia through the olivo-cerebellar pathway.
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Age-dependent impairment of eyeblink conditioning in prion protein-deficient mice.
PLoS ONE
PUBLISHED: 01-01-2013
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Mice lacking the prion protein (PrP(C)) gene (Prnp), Ngsk Prnp (0/0) mice, show late-onset cerebellar Purkinje cell (PC) degeneration because of ectopic overexpression of PrP(C)-like protein (PrPLP/Dpl). Because PrP(C) is highly expressed in cerebellar neurons (including PCs and granule cells), it may be involved in cerebellar synaptic function and cerebellar cognitive function. However, no studies have been conducted to investigate the possible involvement of PrP(C) and/or PrPLP/Dpl in cerebellum-dependent discrete motor learning. Therefore, the present cross-sectional study was designed to examine cerebellum-dependent delay eyeblink conditioning in Ngsk Prnp (0/0) mice in adulthood (16, 40, and 60 weeks of age). The aims of the present study were two-fold: (1) to examine the role of PrP(C) and/or PrPLP/Dpl in cerebellum-dependent motor learning and (2) to confirm the age-related deterioration of eyeblink conditioning in Ngsk Prnp (0/0) mice as an animal model of progressive cerebellar degeneration. Ngsk Prnp (0/0) mice aged 16 weeks exhibited intact acquisition of conditioned eyeblink responses (CRs), although the CR timing was altered. The same result was observed in another line of PrP(c)-deficient mice, ZrchI PrnP (0/0) mice. However, at 40 weeks of age, CR incidence impairment was observed in Ngsk Prnp (0/0) mice. Furthermore, Ngsk Prnp (0/0) mice aged 60 weeks showed more significantly impaired CR acquisition than Ngsk Prnp (0/0) mice aged 40 weeks, indicating the temporal correlation between cerebellar PC degeneration and motor learning deficits. Our findings indicate the importance of the cerebellar cortex in delay eyeblink conditioning and suggest an important physiological role of prion protein in cerebellar motor learning.
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Phospholipase C-beta4 is essential for the progression of the normal sleep sequence and ultradian body temperature rhythms in mice.
PLoS ONE
PUBLISHED: 09-10-2009
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THE SLEEP SEQUENCE: i) non-REM sleep, ii) REM sleep, and iii) wakefulness, is stable and widely preserved in mammals, but the underlying mechanisms are unknown. It has been shown that this sequence is disrupted by sudden REM sleep onset during active wakefulness (i.e., narcolepsy) in orexin-deficient mutant animals. Phospholipase C (PLC) mediates the signaling of numerous metabotropic receptors, including orexin receptors. Among the several PLC subtypes, the beta4 subtype is uniquely localized in the geniculate nucleus of thalamus which is hypothesized to have a critical role in the transition and maintenance of sleep stages. In fact, we have reported irregular theta wave frequency during REM sleep in PLC-beta4-deficient mutant (PLC-beta4-/-) mice. Daily behavioral phenotypes and metabotropic receptors involved have not been analyzed in detail in PLC-beta4-/- mice, however.
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Ethanol enhances both action potential-dependent and action potential-independent GABAergic transmission onto cerebellar Purkinje cells.
Neuropharmacology
PUBLISHED: 04-14-2009
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Ethanol (EtOH) modulates synaptic efficacy in various brain areas, including the cerebellum, which plays a role in motor coordination. Previous studies have shown that EtOH enhances tonic inhibition of cerebellar granule cells, which is one of the possible reasons for the alcohol-induced motor impairment. However, the effects of EtOH on molecular layer interneurons (MLIs) in the mouse cerebellum have remained unknown. Here we found that MLIs were depolarized by EtOH through enhancement of hyperpolarization-activated cationic currents (I(h)). Under physiological conditions, a low EtOH concentration (3-50 mM) caused a small increase in the firing rate of MLIs, whereas, in the presence of blockers for ionotropic glutamate and GABA receptors, EtOH (>or=10 mM) robustly enhanced MLI firing, suggesting that synaptic inputs, which seem to serve as the phasic inhibition, could suppress the EtOH-mediated excitation of MLIs and Purkinje cells (PCs). Even in the absence of synaptic blockers, a high EtOH concentration (100 mM) markedly increased the firing rate of MLIs to enhance GABAergic transmission. Furthermore, 100 mM EtOH-facilitated miniature IPSCs via a mechanism that depended on intracellular cyclic AMP, voltage-dependent Ca(2+) channels, and intracellular Ca(2+) stores, but was independent of I(h) or PKA. The two distinct effects of a high EtOH concentration (>or=100 mM), however, failed to attenuate the EtOH-induced strong depolarization of MLIs. These results suggest that acute exposure to a low EtOH concentration (
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Cerebellar globular cells receive monoaminergic excitation and monosynaptic inhibition from Purkinje cells.
PLoS ONE
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Inhibitory interneurons in the cerebellar granular layer are more heterogeneous than traditionally depicted. In contrast to Golgi cells, which are ubiquitously distributed in the granular layer, small fusiform Lugaro cells and globular cells are located underneath the Purkinje cell layer and small in number. Globular cells have not been characterized physiologically. Here, using cerebellar slices obtained from a strain of gene-manipulated mice expressing GFP specifically in GABAergic neurons, we morphologically identified globular cells, and compared their synaptic activity and monoaminergic influence of their electrical activity with those of small Golgi cells and small fusiform Lugaro cells. Globular cells were characterized by prominent IPSCs together with monosynaptic inputs from the axon collaterals of Purkinje cells, whereas small Golgi cells or small fusiform Lugaro cells displayed fewer and smaller spontaneous IPSCs. Globular cells were silent at rest and fired spike discharges in response to application of either serotonin (5-HT) or noradrenaline. The two monoamines also facilitated small Golgi cell firing, but only 5-HT elicited firing in small fusiform Lugaro cells. Furthermore, globular cells likely received excitatory monosynaptic inputs through mossy fibers. Because globular cells project their axons long in the transversal direction, the neuronal circuit that includes interplay between Purkinje cells and globular cells could regulate Purkinje cell activity in different microzones under the influence of monoamines and mossy fiber inputs, suggesting that globular cells likely play a unique modulatory role in cerebellar motor control.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.