scholarly journals Effect of Noradrenaline on the Facial Stimulation-Evoked Mossy Fiber-Granule Cell Synaptic Transmission in Mouse Cerebellar Cortex

2021 ◽  
Vol 15 ◽  
Author(s):  
Bing-Xue Li ◽  
Hua Jin ◽  
Guang-Jian Zhang ◽  
Li-Na Cui ◽  
Chun-Ping Chu ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Purkinje Cell ◽  
Receptor Antagonist ◽  
Granule Cell ◽  
Adrenergic Receptor ◽  
Granular Layer ◽  
Mossy Fiber ◽  
Cell Activity ◽  
Stimulus Offset

Noradrenaline is an important neuromodulator in the cerebellum. We previously found that noradrenaline depressed cerebellar Purkinje cell activity and climbing fiber–Purkinje cell synaptic transmission in vivo in mice. In this study, we investigated the effect of noradrenaline on the facial stimulation-evoked cerebellar cortical mossy fiber–granule cell synaptic transmission in urethane-anesthetized mice. In the presence of a γ-aminobutyrateA (GABAA) receptor antagonist, air-puff stimulation of the ipsilateral whisker pad evoked mossy fiber–granule cell synaptic transmission in the cerebellar granular layer, which expressed stimulus onset response, N1 and stimulus offset response, N2. Cerebellar surface perfusion of 25 μM noradrenaline induced decreases in the amplitude and area under the curve of N1 and N2, accompanied by an increase in the N2/N1 ratio. In the presence of a GABAA receptor blocker, noradrenaline induced a concentration-dependent decrease in the amplitude of N1, with a half-maximal inhibitory concentration of 25.45 μM. The noradrenaline-induced depression of the facial stimulation-evoked mossy fiber–granule cell synaptic transmission was reversed by additional application of an alpha-adrenergic receptor antagonist or an alpha-2 adrenergic receptor antagonist, but not by a beta-adrenergic receptor antagonist or an alpha-1 adrenergic receptor antagonist. Moreover, application of an alpha-2 adrenergic receptor agonist, UK14304, significantly decreased the synaptic response and prevented the noradrenaline-induced depression. Our results indicate that noradrenaline depresses facial stimulation-evoked mossy fiber–granule cell synaptic transmission via the alpha-2 adrenergic receptor in vivo in mice, suggesting that noradrenaline regulates sensory information integration and synaptic transmission in the cerebellar cortical granular layer.

scholarly journals Chronic Ethanol Exposure Enhances Facial Stimulation-Evoked Mossy Fiber–Granule Cell Synaptic Transmission via GluN2A Receptors in the Mouse Cerebellar Cortex

2021 ◽  
Vol 15 ◽  
Author(s):  
Bing-Xue Li ◽  
Guang-Hui Dong ◽  
Hao-Long Li ◽  
Jia-Song Zhang ◽  
Yan-Hua Bing ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Cerebellar Cortex ◽  
Granule Cell ◽  
Mossy Fiber ◽  
Sensory Information ◽  
Ethanol Exposure ◽  
Chronic Ethanol ◽  
Chronic Ethanol Exposure ◽  
Adult Mice

Sensory information is transferred to the cerebellar cortex via the mossy fiber–granule cell (MF–GC) pathway, which participates in motor coordination and motor learning. We previously reported that chronic ethanol exposure from adolescence facilitated the sensory-evoked molecular layer interneuron–Purkinje cell synaptic transmission in adult mice in vivo. Herein, we investigated the effect of chronic ethanol exposure from adolescence on facial stimulation-evoked MF–GC synaptic transmission in the adult mouse cerebellar cortex using electrophysiological recording techniques and pharmacological methods. Chronic ethanol exposure from adolescence induced an enhancement of facial stimulation-evoked MF–GC synaptic transmission in the cerebellar cortex of adult mice. The application of an N-methyl-D-aspartate receptor (NMDAR) antagonist, D-APV (250 μM), induced stronger depression of facial stimulation-evoked MF–GC synaptic transmission in chronic ethanol-exposed mice compared with that in control mice. Chronic ethanol exposure-induced facilitation of facial stimulation evoked by MF–GC synaptic transmission was abolished by a selective GluN2A antagonist, PEAQX (10 μM), but was unaffected by the application of a selective GluN2B antagonist, TCN-237 (10 μM), or a type 1 metabotropic glutamate receptor blocker, JNJ16259685 (10 μM). These results indicate that chronic ethanol exposure from adolescence enhances facial stimulation-evoked MF–GC synaptic transmission via GluN2A, which suggests that chronic ethanol exposure from adolescence impairs the high-fidelity transmission capability of sensory information in the cerebellar cortex by enhancing the NMDAR-mediated components of MF–GC synaptic transmission in adult mice in vivo.

NMDARs contribute to the facial stimuli-evoked mossy fiber-granule cell synaptic transmission in vivo in mice

2020 ◽  
Vol 736 ◽  
pp. 135285
Author(s):  
Xin-Yuan Zhang ◽  
Guang-Jian Zhang ◽  
Bing-Xue Li ◽  
Yan-Hua Bing ◽  
Bai-Ri Cui ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Granule Cell ◽  
Mossy Fiber ◽  
Facial Stimuli

scholarly journals Efficient generation of reciprocal signals by inhibition

2012 ◽  
Vol 107 (9) ◽  
pp. 2453-2462 ◽  
Author(s):  
Sung-min Park ◽  
Esra Tara ◽  
Kamran Khodakhah
Keyword(s):  
Purkinje Cells ◽  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Cell Activity ◽  
Common Mechanism ◽  
Input Output ◽  
Firing Rates ◽  
Neuronal Computation ◽  
The Brain

Reciprocal activity between populations of neurons has been widely observed in the brain and is essential for neuronal computation. The different mechanisms by which reciprocal neuronal activity is generated remain to be established. A common motif in neuronal circuits is the presence of afferents that provide excitation to one set of principal neurons and, via interneurons, inhibition to a second set of principal neurons. This circuitry can be the substrate for generation of reciprocal signals. Here we demonstrate that this equivalent circuit in the cerebellar cortex enables the reciprocal firing rates of Purkinje cells to be efficiently generated from a common set of mossy fiber inputs. The activity of a mossy fiber is relayed to Purkinje cells positioned immediately above it by excitatory granule cells. The firing rates of these Purkinje cells increase as a linear function of mossy fiber, and thus granule cell, activity. In addition to exciting Purkinje cells positioned immediately above it, the activity of a mossy fiber is relayed to laterally positioned Purkinje cells by a disynaptic granule cell → molecular layer interneuron pathway. Here we show in acutely prepared cerebellar slices that the input-output relationship of these laterally positioned Purkinje cells is linear and reciprocal to the first set. A similar linear input-output relationship between decreases in Purkinje cell firing and strength of stimulation of laterally positioned granule cells was also observed in vivo. Use of interneurons to generate reciprocal firing rates may be a common mechanism by which the brain generates reciprocal signals.

scholarly journals Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse

2020 ◽  
Author(s):  
Timothy S. Balmer ◽  
Carolina Borges-Merjane ◽  
Laurence O. Trussell
Keyword(s):  
Synaptic Transmission ◽  
Mossy Fiber ◽  
Synaptic Cleft ◽  
Synaptic Activity ◽  
Brush Cells ◽  
Incomplete Removal ◽  
Unipolar Brush Cells ◽  
Ambient Glutamate ◽  
Synaptic Responses

AbstractSynapses of glutamatergic mossy fiber onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC’s large dendritic brush. Using brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBC. The source of ambient glutamate was spontaneous, spike-independent exocytosis from the mossy fiber terminal, and its level was dependent on activity of glutamate transporters EAAT1-2. Changing levels of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs and altered the phase of responses to in vivo-like synaptic activity. Unlike classical fast synapses, receptors at the UBC synapse are virtually always exposed to a significant level of glutamate, which varies in a graded manner during transmission.

scholarly journals Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Timothy S Balmer ◽  
Carolina Borges-Merjane ◽  
Laurence O Trussell
Keyword(s):  
Synaptic Transmission ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Synaptic Cleft ◽  
Synaptic Activity ◽  
Brush Cells ◽  
Incomplete Removal ◽  
Unipolar Brush Cells ◽  
Ambient Glutamate

Synapses of glutamatergic mossy fibers onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC's large dendritic brush. Using mouse brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBCs. The source of this ambient glutamate was spontaneous, spike-independent exocytosis from the mossy fiber terminal, and its level was dependent on activity of glutamate transporters EAAT1-2. Increasing levels of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs and altered the phase of responses to in vivo-like synaptic activity. Unlike classical fast synapses, receptors at the UBC synapse are virtually always exposed to a significant level of glutamate, which varies in a graded manner during transmission.

Epinephrine stimulates IL-6 expression in skeletal muscle and C2C12 myoblasts: role of c-Jun NH2-terminal kinase and histone deacetylase activity

2004 ◽  
Vol 286 (5) ◽  
pp. E809-E817 ◽  
Author(s):  
Robert A. Frost ◽  
Gerald J. Nystrom ◽  
Charles H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Receptor Antagonist ◽  
Histone Deacetylase ◽  
Muscle Mass ◽  
Adrenergic Receptor ◽  
Inflammatory Cytokine ◽  
Trichostatin A ◽  
Muscle Cells ◽  
Dependent Manner

Although an individual's genetic makeup is a major determinant of muscle mass, other influences, such as hormones, cytokines, nutrition, and exercise can also modulate muscle size. IL-6 is an important inflammatory cytokine. Mice that overexpress IL-6 fail to thrive and/or have reduced skeletal muscle mass. The purpose of the present study was to determine whether the stress hormone epinephrine increases inflammatory cytokine expression in skeletal muscle and muscle cells. Infusion of epinephrine in vivo for 2 h increased IL-6 protein (15-fold) and mRNA (40-fold) in skeletal muscle but not in liver. Epinephrine had a similar effect in C2C12 muscle cells, where the hormone increased IL-6 protein and mRNA in a dose- and time-dependent manner. Epinephrine-stimulated IL-6 expression was attenuated by the α-adrenergic receptor antagonist phentolamine and completely blocked by either the β1/2-adrenergic receptor antagonist propranalol or the β2-antagonist ICI-118551. The transcriptional inhibitor DRB and the synthetic glucocorticoid dexamethasone also blocked epinephrine-induced IL-6. SP-600125 (a JNK inhibitor) and SB-202190 (a p38 MAP kinase inhibitor) completely blocked epinephrine-induced IL-6 synthesis. Endotoxin and epinephrine given together had a synergistic affect on IL-6 mRNA and protein expression. Trichostatin A (a histone deacetylase inhibitor) blocked both endotoxin- and epinephrine-induced IL-6 expression. These data suggest that epinephrine induces IL-6 synthesis in skeletal muscle in vivo and myocytes in vitro. Epinephrine utilizes predominantly the β1/2-adrenergic receptors to stimulate IL-6 synthesis. Endotoxin and epinephrine synergize to increase IL-6 mRNA expression. Optimal IL-6 synthesis may require both stress kinase and histone deacetylase activity.

Topography of the oculomotor area of the cerebellar vermis in macaques as determined by microstimulation

1987 ◽  
Vol 58 (2) ◽  
pp. 359-378 ◽  
Author(s):  
H. Noda ◽  
T. Fujikado
Keyword(s):  
Eye Movements ◽  
Purkinje Cell ◽  
Neural Activity ◽  
Mossy Fiber ◽  
Cell Activity ◽  
The Other ◽  
Cerebellar Vermis ◽  
Oculomotor Vermis ◽  
Stimulus Current ◽  
Oculomotor Responses

1. Oculomotor responses to microstimulation of the cerebellar vermis of macaque monkeys were investigated by using a magnetic search-coil method. 2. The oculomotor responses were conjugate eye movements with an ipsilateral horizontal component. Analyses of amplitude-velocity and amplitude-duration relationships revealed that the peak eye velocities and the durations of the responses were comparable to those of saccadic eye movements. 3. Systematic mapping with microstimulation disclosed that the region in the cerebellar vermis that yielded saccades with weak stimulus currents was confined to lobule VII in five monkeys but included a part of folium VIc in the other four monkeys. This region coincided with the distribution of the saccade-related neural activity observed in the present study and also corresponded to the vermal folia from which we recorded the burst mossy-fiber units and the oculomotor Purkinje cell activity. 4. The oculomotor vermis was defined as that region of the cerebellar vermis that met the following criteria: 1) saccades were evoked with low-intensity microstimulation (with currents less than 10 microA); 2) vigorous saccade-related neural activity was present; and 3) Purkinje cell discharges were modulated with eye movements. The oculomotor vermis was more circumscribed and located more posteriorly than the vermal cortex explored in previous microstimulation experiments on monkeys. 5. Microstimulation of the oculomotor vermis evoked more or less curved saccades in oblique directions. The horizontal and vertical components were not simultaneous in some saccades: the shorter component started later or ended earlier than the other component and their peak velocities were not always synchronous. 6. The amplitude of the saccade depended on stimulus parameters; microstimulation with 10-12 pulses within a period of approximately 20 ms (500-600 Hz) was shown to be optimal. When the pulses were applied to the white matter or to the granular layer, a stimulus current of 10 microA was sufficient to evoke saccades. When the molecular layer was stimulated, evoked saccades were smaller and frequently curved, and an increase in the stimulus current changed either the initial direction or the trajectory of the saccade. 7. When the stimulus current was carefully controlled and maintained near the threshold, the direction of the saccade evoked from the oculomotor vermis was topographically organized.(ABSTRACT TRUNCATED AT 400 WORDS)

Combinatorial Responses Controlled by Synaptic Inhibition in the Cerebellum Granular Layer

2010 ◽  
Vol 103 (1) ◽  
pp. 250-261 ◽  
Author(s):  
Jonathan Mapelli ◽  
Daniela Gandolfi ◽  
Egidio D'Angelo
Keyword(s):  
Granular Layer ◽  
Mossy Fiber ◽  
Imaging Techniques ◽  
Coincidence Detection ◽  
Acid Type ◽  
Receptor Blockers ◽  
Simultaneous Activation ◽  
Spatial Pattern Separation ◽  
The Individual

The granular layer of cerebellum has been long hypothesized to perform combinatorial operations on incoming signals. Although this assumption is at the basis of main computational theories of cerebellum, it has never been assessed experimentally. Here, by applying high-resolution voltage-sensitive dye imaging techniques, we show that simultaneous activation of two partially overlapping mossy fiber bundles (either with single pulses or high-frequency bursts) can cause combined excitation and combined inhibition, which are compatible with the concepts of coincidence detection and spatial pattern separation predicted by theory. Combined excitation appeared as an area in which the combination of two inputs is greater than the arithmetic sum of the individual inputs and was enhanced by γ-aminobutyric acid type A (GABAA) receptor blockers. Combined inhibition was manifest as an area where two inputs combined resulted in a reduction to less than half of the activity evoked from either one of the two inputs alone and was prevented by GABAA receptor blockers. The combinatorial responses occupied small granular layer regions (∼30 μm diameter), with combined inhibition being interspersed among extended areas of combined excitation. Moreover, the combinatorial effects lasted for tens of milliseconds and combined inhibition occurred only after termination of the stimuli. These combinatorial operations, if engaged by natural input patterns in vivo, may be important to influence incoming impulses organizing spatiotemporal spike sequences to be relayed to Purkinje cells.

scholarly journals CEREBELLAR GRANULE CELLS IN VITRO

1970 ◽  
Vol 45 (2) ◽  
pp. 212-220 ◽  
Author(s):  
Fredrick J. Seil ◽  
Robert M. Herndon
Keyword(s):  
Granule Cell ◽  
Granular Layer ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Light And Electron Microscopy ◽  
Newborn Mouse ◽  
Newborn Mice ◽  
Cerebellar Cultures

The behavior of granule cells in mature cerebellar cultures derived from newborn mice was studied by light and electron microscopy. Many granule cells remained in the explants as an external granular layer. These cells were differentiated, as evidenced by formation of bundles of parallel fibers and by development of synapses between granule cell axons and Purkinje cell branchlet spines, and between Golgi cell axons and granule cell dendrites. Although the over-all architecture of the cerebellar explants after 18–33 days in vitro was similar to that of the newborn mouse, the evident differentiation of the granule cells suggested that interneuronal relationships resemble those of the mature cerebellum in vivo.

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