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1.
Nat Rev Neurosci ; 12(6): 327-44, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21544091

RESUMEN

Neurons are generally considered to communicate information by increasing or decreasing their firing rate. However, in principle, they could in addition convey messages by using specific spatiotemporal patterns of spiking activities and silent intervals. Here, we review expanding lines of evidence that such spatiotemporal coding occurs in the cerebellum, and that the olivocerebellar system is optimally designed to generate and employ precise patterns of complex spikes and simple spikes during the acquisition and consolidation of motor skills. These spatiotemporal patterns may complement rate coding, thus enabling precise control of motor and cognitive processing at a high spatiotemporal resolution by fine-tuning sensorimotor integration and coordination.


Asunto(s)
Potenciales de Acción/fisiología , Cerebelo/fisiología , Red Nerviosa/fisiología , Neuronas/fisiología , Animales , Plasticidad Neuronal/fisiología
2.
Cerebellum ; 14(5): 506-15, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25735968

RESUMEN

The cerebellum plays an important role in the coordination and refinement of movements and cognitive processes. Recently, it has been shown that the main output neuron of the cerebellar cortex, i.e., the Purkinje cell, can show a different firing behavior dependent on its intrinsic electrophysiological properties. Yet, to what extent a different nature of mossy fiber inputs can influence the firing behavior of cerebellar cortical neurons remains to be elucidated. Here, we compared the firing rate and regularity of mossy fibers and neurons in two different regions of cerebellar cortex. One region intimately connected with the cerebral cortex, i.e., lobules VI/VII of the neocerebellum, and another one strongly connected with the vestibular apparatus, i.e., lobule X of the archaeocerebellum. Given their connections, we hypothesized that activity in neurons in lobules VI/VII and lobule X may be expected to be more phasic and tonic, respectively. Using whole-cell and cell-attached recordings in vivo in anesthetized mice, we show that the mossy fiber inputs to these functionally distinct areas of the cerebellum differ in that the irregularity and bursty character of their firing is significantly greater in lobules VI/VII than in lobule X. Importantly, this difference in mossy fiber regularity is propagated through the granule cells at the input stage to the Purkinje cells and molecular layer interneurons, ultimately resulting in different regularity of simple spikes. These data show that the firing behavior of cerebellar cortical neurons does not only reflect particular intrinsic properties but also an interesting interplay with the innate activity at the input stage.


Asunto(s)
Potenciales de Acción/fisiología , Corteza Cerebelosa/citología , Fibras Nerviosas/fisiología , Red Nerviosa/fisiología , Neuronas/fisiología , Animales , Estimulación Eléctrica , Potenciales Postsinápticos Excitadores/fisiología , Ratones , Ratones Endogámicos C57BL , Modelos Neurológicos , Neuronas/clasificación
3.
Proc Natl Acad Sci U S A ; 107(18): 8410-5, 2010 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-20395550

RESUMEN

The output of the cerebellar cortex is controlled by two main inputs, (i.e., the climbing fiber and mossy fiber-parallel fiber pathway) and activations of these inputs elicit characteristic effects in its Purkinje cells: that is, the so-called complex spikes and simple spikes. Target neurons of the Purkinje cells in the cerebellar nuclei show rebound firing, which has been implicated in the processing and storage of motor coordination signals. Yet, it is not known to what extent these rebound phenomena depend on different modes of Purkinje cell activation. Using extracellular as well as patch-clamp recordings, we show here in both anesthetized and awake rodents that simple and complex spike-like train stimuli to the cerebellar cortex, as well as direct activation of the inferior olive, all result in rebound increases of the firing frequencies of cerebellar nuclei neurons for up to 250 ms, whereas single-pulse stimuli to the cerebellar cortex predominantly elicit well-timed spiking activity without changing the firing frequency of cerebellar nuclei neurons. We conclude that the rebound phenomenon offers a rich and powerful mechanism for cerebellar nuclei neurons, which should allow them to differentially process the climbing fiber and mossy fiber inputs in a physiologically operating cerebellum.


Asunto(s)
Núcleos Cerebelosos/fisiología , Animales , Conducta Animal , Ratones , Ratones Endogámicos C57BL , Técnicas de Placa-Clamp , Ratas , Ratas Wistar
4.
iScience ; 25(7): 104641, 2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35800775

RESUMEN

The basilar pontine nuclei (bPN) are known to receive excitatory input from the entire neocortex and constitute the main source of mossy fibers to the cerebellum. Various potential inhibitory afferents have been described, but their origin, synaptic plasticity, and network function have remained elusive. Here we identify the mesodiencephalic junction (MDJ) as a prominent source of monosynaptic GABAergic inputs to the bPN. We found no evidence that these inputs converge with motor cortex (M1) inputs at the single neuron or at the local network level. Tracing the inputs to GABAergic MDJ neurons revealed inputs to these neurons from neocortical areas. Additionally, we observed little short-term synaptic facilitation or depression in afferents from the MDJ, enabling MDJ inputs to carry sign-inversed neocortical inputs. Thus, our results show a prominent source of GABAergic inhibition to the bPN that could enrich input to the cerebellar granule cell layer.

5.
Elife ; 92020 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-32022688

RESUMEN

Cerebellar granule cells (GCs) make up the majority of all neurons in the vertebrate brain, but heterogeneities among GCs and potential functional consequences are poorly understood. Here, we identified unexpected gradients in the biophysical properties of GCs in mice. GCs closer to the white matter (inner-zone GCs) had higher firing thresholds and could sustain firing with larger current inputs than GCs closer to the Purkinje cell layer (outer-zone GCs). Dynamic Clamp experiments showed that inner- and outer-zone GCs preferentially respond to high- and low-frequency mossy fiber inputs, respectively, enabling dispersion of the mossy fiber input into its frequency components as performed by a Fourier transformation. Furthermore, inner-zone GCs have faster axonal conduction velocity and elicit faster synaptic potentials in Purkinje cells. Neuronal network modeling revealed that these gradients improve spike-timing precision of Purkinje cells and decrease the number of GCs required to learn spike-sequences. Thus, our study uncovers biophysical gradients in the cerebellar cortex enabling a Fourier-like transformation of mossy fiber inputs.


The timing of movements such as posture, balance and speech are coordinated by a region of the brain called the cerebellum. Although this part of the brain is small, it contains a huge number of tiny nerve cells known as granule cells. These cells make up more than half the nerve cells in the human brain. But why there are so many is not well understood.The cerebellum receives signals from sensory organs, such as the ears and eyes, which are passed on as electrical pulses from nerve to nerve until they reach the granule cells. These electrical pulses can have very different repetition rates, ranging from one pulse to a thousand pulses per second. Previous studies have suggested that granule cells are a uniform population that can detect specific patterns within these electrical pulses. However, this would require granule cells to identify patterns in signals that have a range of different repetition rates, which is difficult for individual nerve cells to do.To investigate if granule cells are indeed a uniform population, Straub, Witter, Eshra, Hoidis et al. measured the electrical properties of granule cells from the cerebellum of mice. This revealed that granule cells have different electrical properties depending on how deep they are within the cerebellum. These differences enabled the granule cells to detect sensory signals that had specific repetition rates: signals that contained lots of repeats per second were relayed by granule cells in the lower layers of the cerebellum, while signals that contained fewer repeats were relayed by granule cells in the outer layers.This ability to separate signals based on their rate of repetition is similar to how digital audio files are compressed into an MP3. Computer simulations suggested that having granule cells that can detect specific rates of repetition improves the storage capacity of the brain.These findings further our understanding of how the cerebellum works and the cellular mechanisms that underlie how humans learn and memorize the timing of movement. This mechanism of separating signals to improve storage capacity may apply to other regions of the brain, such as the hippocampus, where differences between nerve cells have also recently been reported.


Asunto(s)
Corteza Cerebelosa , Neuronas , Animales , Fenómenos Biofísicos/fisiología , Corteza Cerebelosa/citología , Corteza Cerebelosa/metabolismo , Corteza Cerebelosa/fisiología , Análisis de Fourier , Ratones , Modelos Neurológicos , Fibras Nerviosas/metabolismo , Fibras Nerviosas/fisiología , Neuronas/citología , Neuronas/metabolismo , Neuronas/fisiología , Células de Purkinje/citología , Células de Purkinje/metabolismo , Células de Purkinje/fisiología , Potenciales Sinápticos/fisiología , Sustancia Blanca/citología , Sustancia Blanca/metabolismo , Sustancia Blanca/fisiología
6.
Cerebellum ; 7(4): 547-58, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-19082682

RESUMEN

Homozygous tottering mice are spontaneous ataxic mutants, which carry a mutation in the gene encoding the ion pore of the P/Q-type voltage-gated calcium channels. P/Q-type calcium channels are prominently expressed in Purkinje cell terminals, but it is unknown to what extent these inhibitory terminals in tottering mice are affected at the morphological and electrophysiological level. Here, we investigated the distribution and ultrastructure of their Purkinje cell terminals in the cerebellar nuclei as well as the activities of their target neurons. The densities of Purkinje cell terminals and their synapses were not significantly affected in the mutants. However, the Purkinje cell terminals were enlarged and had an increased number of vacuoles, whorled bodies, and mitochondria. These differences started to occur between 3 and 5 weeks of age and persisted throughout adulthood. Stimulation of Purkinje cells in adult tottering mice resulted in inhibition at normal latencies, but the activities of their postsynaptic neurons in the cerebellar nuclei were abnormal in that the frequency and irregularity of their spiking patterns were enhanced. Thus, although the number of their terminals and their synaptic contacts appear quantitatively intact, Purkinje cells in tottering mice show several signs of axonal damage that may contribute to altered postsynaptic activities in the cerebellar nuclei.


Asunto(s)
Ataxia/genética , Ataxia/fisiopatología , Canales de Calcio Tipo Q/fisiología , Núcleos Cerebelosos/fisiología , Ratones Mutantes Neurológicos/fisiología , Células de Purkinje/fisiología , Envejecimiento/fisiología , Animales , Calbindinas , Canales de Calcio Tipo Q/genética , Núcleos Cerebelosos/crecimiento & desarrollo , Núcleos Cerebelosos/fisiopatología , Núcleos Cerebelosos/ultraestructura , Cruzamientos Genéticos , Electroencefalografía , Electrofisiología , Femenino , Masculino , Trastornos Mentales/genética , Ratones , Ratones Endogámicos C57BL , Terminaciones Nerviosas/fisiología , Terminaciones Nerviosas/ultraestructura , Reacción en Cadena de la Polimerasa , Células de Purkinje/ultraestructura , Proteína G de Unión al Calcio S100/análisis
7.
Neuron ; 100(3): 564-578.e3, 2018 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-30293822

RESUMEN

Correlated neuronal activity at various timescales plays an important role in information transfer and processing. We find that in awake-behaving mice, an unexpectedly large fraction of neighboring Purkinje cells (PCs) exhibit sub-millisecond synchrony. Correlated firing usually arises from chemical or electrical synapses, but, surprisingly, neither is required to generate PC synchrony. We therefore assessed ephaptic coupling, a mechanism in which neurons communicate via extracellular electrical signals. In the neocortex, ephaptic signals from many neurons summate to entrain spiking on slow timescales, but extracellular signals from individual cells are thought to be too small to synchronize firing. Here we find that a single PC generates sufficiently large extracellular potentials to open sodium channels in nearby PC axons. Rapid synchronization is made possible because ephaptic signals generated by PCs peak during the rising phase of action potentials. These findings show that ephaptic coupling contributes to the prevalent synchronization of nearby PCs.


Asunto(s)
Potenciales de Acción/fisiología , Cerebelo/citología , Cerebelo/fisiología , Células de Purkinje/fisiología , Animales , Cerebelo/química , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Técnicas de Cultivo de Órganos , Células de Purkinje/química
9.
PLoS One ; 11(11): e0165887, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27851801

RESUMEN

Cerebellar nuclei neurons integrate sensorimotor information and form the final output of the cerebellum, projecting to premotor brainstem targets. This implies that, in contrast to specialized neurons and interneurons in cortical regions, neurons within the nuclei encode and integrate complex information that is most likely reflected in a large variation of intrinsic membrane properties and integrative capacities of individual neurons. Yet, whether this large variation in properties is reflected in a heterogeneous physiological cell population of cerebellar nuclei neurons with well or poorly defined cell types remains to be determined. Indeed, the cell electrophysiological properties of cerebellar nuclei neurons have been identified in vitro in young rodents, but whether these properties are similar to the in vivo adult situation has not been shown. In this comprehensive study we present and compare the in vivo properties of 144 cerebellar nuclei neurons in adult ketamine-xylazine anesthetized mice. We found regularly firing (N = 88) and spontaneously bursting (N = 56) neurons. Membrane-resistance, capacitance, spike half-width and firing frequency all widely varied as a continuum, ranging from 9.63 to 3352.1 MΩ, from 6.7 to 772.57 pF, from 0.178 to 1.98 ms, and from 0 to 176.6 Hz, respectively. At the same time, several of these parameters were correlated with each other. Capacitance decreased with membrane resistance (R2 = 0.12, P<0.001), intensity of rebound spiking increased with membrane resistance (for 100 ms duration R2 = 0.1503, P = 0.0011), membrane resistance decreased with membrane time constant (R2 = 0.045, P = 0.031) and increased with spike half-width (R2 = 0.023, P<0.001), while capacitance increased with firing frequency (R2 = 0.29, P<0.001). However, classes of neuron subtypes could not be identified using merely k-clustering of their intrinsic firing properties and/or integrative properties following activation of their Purkinje cell input. Instead, using whole-cell parameters in combination with morphological criteria revealed by intracellular labelling with Neurobiotin (N = 18) allowed for electrophysiological identification of larger (29.3-50 µm soma diameter) and smaller (< 21.2 µm) cerebellar nuclei neurons with significant differences in membrane properties. Larger cells had a lower membrane resistance and a shorter spike, with a tendency for higher capacitance. Thus, in general cerebellar nuclei neurons appear to offer a rich and wide continuum of physiological properties that stand in contrast to neurons in most cortical regions such as those of the cerebral and cerebellar cortex, in which different classes of neurons operate in a narrower territory of electrophysiological parameter space. The current dataset will help computational modelers of the cerebellar nuclei to update and improve their cerebellar motor learning and performance models by incorporating the large variation of the in vivo properties of cerebellar nuclei neurons. The cellular complexity of cerebellar nuclei neurons may endow the nuclei to perform the intricate computations required for sensorimotor coordination.


Asunto(s)
Núcleos Cerebelosos/fisiología , Fenómenos Electrofisiológicos , Neuronas/fisiología , Animales , Ratones Endogámicos C57BL , Neuronas/citología , Fenómenos Ópticos , Células de Purkinje/fisiología
10.
Neuron ; 91(2): 312-9, 2016 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-27346533

RESUMEN

Purkinje cells (PCs) provide the sole output from the cerebellar cortex. Although PCs are well characterized on many levels, surprisingly little is known about their axon collaterals and their target neurons within the cerebellar cortex. It has been proposed that PC collaterals transiently control circuit assembly in early development, but it is thought that PC-to-PC connections are subsequently pruned. Here, we find that all PCs have collaterals in young, juvenile, and adult mice. Collaterals are restricted to the parasagittal plane, and most synapses are located in close proximity to PCs. Using optogenetics and electrophysiology, we find that in juveniles and adults, PCs make synapses onto other PCs, molecular layer interneurons, and Lugaro cells, but not onto Golgi cells. These findings establish that PC output can feed back and regulate numerous circuit elements within the cerebellar cortex and is well suited to contribute to processing in parasagittal zones.


Asunto(s)
Axones/fisiología , Corteza Cerebelosa/fisiología , Interneuronas/fisiología , Células de Purkinje/fisiología , Sinapsis/fisiología , Animales , Núcleos Cerebelosos/fisiología , Retroalimentación
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