Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Purkinje neuron”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2006

Interaction of Kv3 potassium channels and resurgent sodium current influences the rate of spontaneous firing of Purkinje neurons.

Purkinje neurons spontaneously generate action potentials in the absence of synaptic drive and thereby exert a tonic, yet plastic, input to their target cells in the deep cerebellar nuclei. Purkinje neurons express two ionic currents with biophysical properties that are specialized for high-frequency firing: resurgent sodium currents and potassium currents mediated by Kv3.3. How these ionic currents determine the intrinsic activity of Purkinje neurons has only partially been understood. Purkinje neurons from mutant mice lacking Kv3.3 have a reduced rate of spontaneous firing. Dynamic-clamp recordings demonstrated that normal firing rates are rescued by inserting artificial Kv3 currents into Kv3.3 knock-out Purkinje neurons. Numerical simulations indicated that Kv3.3 increases the spontaneous firing rate via cooperation with resurgent sodium currents. We conclude that the rate of spontaneous action potential firing of Purkinje neurons is controlled by the interaction of Kv3.3 potassium currents and resurgent sodium currents.

Action Potentials↗
PubMed1994

Continuous network of endoplasmic reticulum in cerebellar Purkinje neurons.

Purkinje neurons in rat cerebellar slices injected with an oil drop saturated with 1,1'-dihexadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate [DiIC16(3) or DiI] to label the endoplasmic reticulum were observed by confocal microscopy. DiI spread throughout the cell body and dendrites and into the axon. DiI spreading is due to diffusion in a continuous bilayer and is not due to membrane trafficking because it also spreads in fixed neurons. DiI stained such features of the endoplasmic reticulum as densities at branch points, reticular networks in the cell body and dendrites, nuclear envelope, spines, and aggregates formed during anoxia nuclear envelope, spines, and aggregates formed during anoxia in low extracellular Ca2+. In cultured rat hippocampal neurons, where optical conditions provide more detail, DiI labeled a clearly delineated network of endoplasmic reticulum in the cell body. We conclude that there is a continuous compartment of endoplasmic reticulum extending from the cell body throughout the dendrites. This compartment may coordinate and integrate neuronal functions.

Animals↗
PubMed1993

Differential effects of ethanol on the firing rates of Golgi-like neurons and Purkinje neurons in cerebellar slices in vitro.

Previous studies have demonstrated that ethanol (EtOH) inhibits the firing rate of Purkinje neurons both in vitro and in vivo. However, little is known about the response of cerebellar interneurons to EtOH. In this report, we describe the effects of locally applied EtOH on the firing of one type of cerebellar interneuron, tentatively identified as Golgi neurons, and on Purkinje cells in brain slices in vitro. The Golgi neurons were excited by EtOH, whereas EtOH depressed the firing rate of Purkinje neurons. To the best of our knowledge, this is the first report of responses of cerebellar Golgi neurons to local applications of EtOH.

Animals↗
PubMed2006

Unravelling the Purkinje neuron.

Purkinje cells, the first nerve cells to be described, are still one of the most interesting and useful experimental models to investigate different aspects of neural function. This special issue of The Cerebellum is dedicated to this very special neuron and contains a number of articles covering different topics of Purkinje cell research, from developmental neurobiology to neurophysiology and neuropathology. More than 150 years after their discovery, Purkinje cells remain one of the most popular neurons in the neuroscience community.

Animals↗
PubMed1994

Toxicity of an antitumor ribonuclease to Purkinje neurons.

Purkinje cell toxicity is one of the characteristic features of the Gordon phenomenon, a syndrome manifested by ataxia, muscular rigidity, paralysis, and tremor that may lead to death (Gordon, 1933). Two members of the RNase superfamily found in humans, EDN (eosinophil-derived neurotoxin) and ECP (eosinophil cationic protein), cause the Gordon phenomenon when injected intraventricularly into guinea pigs or rabbits. We have found that another member of the RNase superfamily, an antitumor protein called onconase, isolated from Rana pipiens oocytes and early embryos, will also cause the Gordon phenomenon when injected into the cerebrospinal fluid of guinea pigs at a dose similar to that of EDN (LD50, 3-4 micrograms). Neurologic abnormalities of onconase-treated animals were indistinguishable from those of EDN-treated animals, and histology showed dramatic Purkinje cell loss in the brains of onconase-treated animals. The neurotoxic activity of onconase correlates with ribonuclease activity. Onconase modified by iodoacetic acid to eliminate 70% and 98% of the ribonuclease activity of the native enzyme displays a similar decrease in ability to cause the Gordon phenomenon. In contrast, the homologous bovine pancreatic RNase A injected intraventricularly at a dose 5000 times greater than the LD50 dose of EDN or onconase is not toxic and does not cause the Gordon phenomenon. A comparison of the RNase activities of EDN, onconase, and bovine pancreatic RNase A using three pancreatic RNA substrates demonstrates that onconase is orders of magnitude less active enzymatically than EDN and RNase A. Thus, another member of the RNase superfamily in addition to EDN and ECP can cause the Gordon phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1999

Entire course and distinct phases of day-lasting depression of miniature EPSC amplitudes in cultured Purkinje neurons.

The cerebellar long-term depression (LTD) is the long-lasting reduction of transmission efficacy at the granule neuron-Purkinje neuron (G-P) synapses and is a candidate mechanism for the motor learning. Despite extensive studies on its induction and expression mechanisms, it has not been known how long the LTD lasts. The LTD is accompanied by the decrease in the postsynaptic responsiveness to glutamate, the transmitter at G-P synapses. Therefore, during the LTD, the amplitude of miniature EPSCs (mEPSCs) at G-P synapses should decrease. We studied the depression of mEPSC amplitudes (DME) as a possible contributing factor for the LTD and found that the conditioning treatment of cultured cerebellar neurons with 50 mM K(+) and 100 microM glutamate, an analogous condition used to induce the LTD, induced the long-lasting DME. The mEPSC amplitudes recovered to the original level 48 hr after the 5 min conditioning treatment. Changing the duration of the conditioning revealed that the DME consisted of two distinct phases: the early phase lasting for a few hours and the late phase for >1 d. The latter was distinguished from the former by its requirement of prolonged conditioning treatment and syntheses of mRNA and protein for the induction. There were critical periods for mRNA and protein syntheses. The critical period for protein synthesis was much longer than that for mRNA synthesis. These results demonstrate that the DME lasts for 1-2 d and that it consists of two phases, whose induction and maintenance mechanisms are distinct.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2006

Developmental expression of Na+ currents in mouse Purkinje neurons.

As Purkinje neurons mature during postnatal development, they change from electrically quiescent to active and exhibit high frequency spontaneous action potentials. This change in electrical activity is determined by both alteration in ion channel expression and the acquisition of synaptic input. To gain a better understanding of the development the intrinsic electrical properties of these neurons, acutely isolated Purkinje neurons from mice aged postnatal day 4 (P4) to P18 were examined. This included recording action potential frequency, threshold, height and slope, and input resistance and capacitance. Changes in a number of these properties were observed, suggesting significant changes in voltage-gated Na(+) currents. Because voltage-gated Na(+) currents, including the transient, resurgent and persistent currents, are known to play important roles in generating spontaneous action potentials, the developmental changes in these currents were examined. A large increase in the density of transient current, resurgent current and persistent current was observed at times corresponding with changes in action potential properties. Interestingly, the developmental up-regulation of the persistent current and resurgent current occurred at rate which was faster than the up-regulation of the transient current. Moreover, the relative amplitudes of the persistent and resurgent currents increased in parallel, suggesting that they share a common basis. The data indicate that developmental up-regulation of Na(+) currents plays a key role in the acquisition of Purkinje neuron excitability.

Action Potentials↗
PubMed2004

Calcium-activated potassium channels are selectively coupled to P/Q-type calcium channels in cerebellar Purkinje neurons.

Cerebellar Purkinje neurons fire spontaneously in the absence of synaptic transmission. P/Q-type voltage-gated calcium channels and calcium-activated potassium channels are required for normal spontaneous activity. Blocking P/Q-type calcium channels paradoxically mimics the effects of blocking calcium-activated potassium channels. Thus, an important function of the P/Q-type calcium channels is to provide calcium for activation of calcium-activated potassium channels. Purkinje neurons express several classes of voltage-gated calcium channels, and the P/Q- and T-type channels make comparable contributions to total calcium entry after an action potential. Here we demonstrate that calcium-activated potassium channels are activated exclusively by calcium entering through P/Q-type voltage-gated calcium channels. This selective coupling is maintained even when calcium flux through voltage-gated channels is increased by increasing the extracellular calcium concentration. Small decreases in P/Q current density are likely to alter spontaneous activity of Purkinje neurons via decreased recruitment of calcium-activated potassium channels. In both human and murine animal models, mutations that decrease P/Q current density in Purkinje neurons also cause cerebellar ataxia. Alterations in the spontaneous activity of Purkinje neurons may be an important contributing factor to the ataxia in these subjects.

Action Potentials↗
PubMed1995

Depolarization-induced calcium signals in the somata of cerebellar Purkinje neurons.

Cerebellar Purkinje neurons express voltage-gated Ca2+ channels that are located on their somata and dendrites. Previous reports, based on microelectrode recordings and fura-2 Ca2+ imaging, suggested that depolarization-mediated intracellular Ca2+ signaling is confined almost completely to the dendrites. We investigated the spatial distribution of depolarization-induced Ca2+ signals in Purkinje neurons by applying whole-cell patch-clamp recordings combined with fluorometric Ca2+ imaging to cerebellar slices. Under our recording conditions, depolarizing pulses produced the dendritic but also large somatic Ca2+ signals. By selective perfusion of the slice with a Ca(2+)-free EGTA-containing solution, we could isolate experimentally Ca2+ signals in somata and dendrites, respectively. Moreover, experiments performed on cerebellar slices from young rats (up to postnatal day 6), in which Purkinje neurons are almost completely devoid of dendrites, showed that Ca2+ currents produced by the activation of somatic Ca2+ channels are associated with Ca2+ transients similar to those seen in the somata of adult Purkinje neurons. Our results strongly indicate that the depolarization-induced somatic Ca2+ signals are caused by Ca2+ entry through voltage-gated channels located on the somatic membrane of Purkinje neurons.

Animals↗
PubMed1980

The Purkinje neuron: II. Electron microscopic analysis of the mature Purkinje neuron in organotypic culture.

Purkinje neurons of organotypic cultures were investigated electron microscopically following their analysis with the Golgi technique. The purpose of this study was to critically examine the issue of synaptic specificity in CNS cultures. The unique finding was the synaptic cluster, a terminal which engulfs many Purkinje spines. In the neuropil and on the major dendrites, this synaptic arrangement was interpreted to be a hypertrophic parallel fiber, representing a type of synaptic modulation. The terminals on the somatic spines are also in the form of clusters; some or all of these spines were thought to have developed to form synapses with the climbing fiber. In the absence of this afferent, the parallel fiber--a competing system--takes over the site. This represents a form of synaptic plasticity in these cultures. The inhibitory synaptic relationships were maintained on the soma and dendrites, but it was found that the basket synapses did not quantitatively encase the soma as is seen in the intact animal. Mossy-type terminals were found occasionally synapsing with Purkinje dendritic spines, as has been seen in agranular cerebellum in animals. These mossy terminals are presently thought to originate from the deep cerebellar nuclei within these cultures. Synaptic errors were rarely encountered. It is concluded that this preparation develops in accordance with established neurobiological principles, that the Purkinje neuron reaches a mature state in culture, and that this model has a sound anatomical basis for further experimental work.

Animals↗
PubMed2003

Somatic and dendritic small-conductance calcium-activated potassium channels regulate the output of cerebellar Purkinje neurons.

Cerebellar Purkinje neurons provide the sole output of the cerebellar cortex and play a crucial role in motor coordination and maintenance of balance. They are spontaneously active, and it is thought that they encode timing signals in the rate and pattern of their activity. An understanding of factors that control their excitability is important for delineating their computational role in the cerebellum. We evaluated the role of small-conductance calcium-activated potassium (SK) channels in the regulation of activity of mouse and rat Purkinje neurons. We find that somatic SK channels effectively limit the maximum firing rate of Purkinje neurons; when SK channels are blocked by the specific antagonists apamin or scyllatoxin, cells fire spontaneously at rates as high as 500 spikes per second. Dendritic SK channels, however, control primarily the extent to which dendrites contribute to the firing rate of Purkinje cells. Given their presence in the dendrites, it is likely that SK channels in the proximal dendrites govern the efficacy of dendrosomatic electrical coupling. When studied under physiological conditions, it is found that SK channels play the same role in controlling the excitability of adult Purkinje neurons as they do in young cells.

Action Potentials↗
PubMed1989

Unique properties of non-N-methyl-D-aspartate excitatory responses in cultured purkinje neurons.

Cerebellar Purkinje neurons respond to glutamate and to the agonists quisqualate (QA) and kainate (KA) with prolonged, multiphasic, voltage-dependent depolarizations. In contrast, N-methyl-D-aspartate (NMDA) at equivalent doses is not effective as an agonist for Purkinje neurons. The responses to QA and KA are reduced by extracellular Cd2+ (30 microM), by increased Mg2+ or Ca2+ (12 mM), and by the glutamate antagonist kynurenic acid (1 mM) but not by the NMDA-selective antagonist 2-amino-5-phosphonovalerate (100 microM). The short pressure application of 1 microM QA (less than or equal to 0.5 s) produces a response often exceeding 1 min in duration, which consists of several phases: rapid initial depolarization, followed by a long plateau, repolarization, and a subsequent small hyperpolarization. A similar response is evoked by glutamate and KA at higher doses (30-50 microM). The initial and plateau depolarizations are dependent on Na+, being reduced by substitution of external Na+ with sucrose or choline, but are not affected by the Na+ channel blocker tetrodotoxin. Rectification, observed at hyperpolarized potentials below -60 mV set by current clamp, is attributed in part to an intrinsic voltage sensitivity of the agonist-activated response. Both the duration and the magnitude of the excitatory responses were found to be voltage-dependent. Single-channel recordings of a Ca2+-sensitive K+ channel, activated selectively during the excitatory response, suggest that intracellular Ca2+ increases during the plateau phase. Certain properties of the excitatory responses in the Purkinje neuron resemble those associated with NMDA-receptor activation in other regions of the central nervous system, including voltage-sensitive rectification, blockade by divalent cations, and the induction of increased intracellular Ca2+ during the excitatory response. These unique properties may enable the Purkinje neuron to express both rapid and long-term effects of glutamatergic transmission with non-NMDA receptors alone.

Action Potentials↗
PubMed2006

Cell-type specific proximity of centromeric domains of one homologue each of chromosomes 2 and 11 in nuclei of cerebellar Purkinje neurons.

In Purkinje neurons of the mouse cerebellum, the centromeres of several chromosomes are placed in close proximity to form a distinct pattern of clusters and exhibit reproducible spatial redistributions during development. In granule neurons, an adjacent cell type in the cerebellum, the pattern, size, and number of centromeric aggregations are different from those of Purkinje neurons. The present work was undertaken to test the hypothesis that the same chromosomes form part of one aggregate in a cell-type-specific manner. Fluorescence in situ hybridization (FISH) with chromosome-specific paracentromeric probes was used to identify centromeric regions of individual chromosomes in cerebellar Purkinje and granule neurons of the adult mouse. When pairs of centromeric probes were used in two-color FISH, one homologue each of chromosomes 2 and 11 were routinely found close to each other in Purkinje neurons but not in granule neurons. This finding of specific proximity was limited to the pair 2 and 11, out of the ten chromosome pairs that were randomly selected and studied. Our results indicate that, in adult Purkinje neurons, a cell-type-specific spatial proximity is present between centromeric domains of one homologue each of chromosomes 2 and 11.

Animals↗
PubMed1999

Chronic ethanol treatment alters AMPA-induced calcium signals in developing Purkinje neurons.

Cerebellar Purkinje neurons developing in culture were treated chronically with 30 mM (140 mg%; 3-11 days in vitro) ethanol to study the actions of prolonged ethanol exposure on responses to exogenous application of AMPA, a selective agonist at the AMPA subtype of ionotropic glutamate receptors. There was no consistent difference between control and chronic ethanol-treated neurons in resting membrane potential, input resistance, or the amplitude or duration of the membrane responses to AMPA (1 or 5 microM applied by brief microperfusion) as measured using the nystatin patch method of whole cell recording. In additional studies, the Ca2+ signal to AMPA was examined using the Ca2+ sensitive dye fura-2. The mean peak Ca2+ signal elicited by 5 microM AMPA was enhanced in the dendritic region (but not the somatic region) of chronic ethanol-treated Purkinje neurons compared to control neurons. In contrast, there was no difference between control and chronic ethanol-treated neurons in the peak amplitude of the Ca2+ signal to 1 microM AMPA, whereas the recovery of the Ca2+ signals was more rapid in both somatic and dendritic regions of ethanol-treated neurons. Resting Ca2+ levels in the somatic and dendritic regions were similar between control and ethanol-treated neurons. These data show that the membrane and Ca2+ responses to AMPA in Purkinje neurons are differentially affected by prolonged ethanol exposure during development. Moreover, chronic ethanol exposure produces a selective enhancement of AMPA-evoked dendritic Ca2+ signals under conditions reflecting intense activation (i.e., 5 microM AMPA), whereas both somatic and dendritic Ca2+ signals are attenuated with smaller levels of activation (i.e., 1 microM AMPA). Because Ca2+ is an important regulator of numerous intracellular functions, chronic ethanol exposure during development could produce widespread changes in the development and function of the cerebellum.

Animals↗
PubMed1997

Induction of long-term depression and rebound potentiation by inositol trisphosphate in cerebellar Purkinje neurons.

Cerebellar Purkinje neurons receive two major excitatory inputs, the climbing fibers (CFs) and parallel fibers (PFs). Simultaneous, repeated activation of CFs and PFs results in the long-term depression (LTD) of the amplitude of PF-evoked synaptic currents. To induce LTD, activation of CFs may be substituted with depolarization of the Purkinje neuron to turn on voltage-activated calcium channels and increase the intracellular calcium concentration. The role of PFs in the induction of LTD, however, is less clear. PFs activate glutamate metabotropic receptors that increase phosphoinositide turnover and elevate cytosolic inositol 1,4,5-trisphosphate (InsP3). It has been proposed that calcium release from intracellular stores via InsP3 receptors may be important in the induction of LTD. We studied the role of InsP3 in the induction of LTD by photolytic release of InsP3 from its biologically inactive "caged" precursor in voltage-clamped Purkinje neurons in acutely prepared cerebellar slices. We find that InsP3-evoked calcium release is as effective in LTD induction as activation of PFs. InsP3-induced LTD was prevented by calcium chelator 1,2-bis(2-amino phenoxy)ethane-N,N,N', N'-tetraacetic acid. LTD produced either by repeated activation of PFs combined with depolarization (PF+DeltaV), or by InsP3 combined with depolarization (InsP3+DeltaV) saturated at approximately 50%. Maximal LTD induced by PF+DeltaV could not be further increased by InsP3+DeltaV and vice versa, which suggests that both protocols for induction of LTD share a common path. In addition to inducing LTD, photo-release of InsP3+DeltaV resulted in the rebound potentiation of inhibitory synaptic currents. In the presence of heparin, an InsP3 receptor antagonist, repeated activation of PF+DeltaV failed to induce LTD, suggesting that InsP3 receptors play an important role in LTD induction under physiological conditions.

Animals↗
PubMed1985

Selective extraction of small and large molecules from the cerebrospinal fluid by Purkinje neurons.

Cerebellar Purkinje neurons accumulated propidium iodide, granular blue, and horseradish peroxidase conjugated to wheat germ agglutinin but not unconjugated horseradish peroxidase, bisbenzimide, or Evans blue when these compounds were infused into the lateral cerebral ventricles of awake, unrestrained rats. Accumulation of propidium iodide by Purkinje neurons of the vermis was associated with a reproducible behavioral abnormality characterized by truncal tremor, ataxia, and nystagmus. Both the accumulation of propidium iodide in Purkinje cells and the behavioral abnormality were prevented by prior intracerebroventricular administration of ouabain or colchicine, drugs that block neuronal transport processes. The ability of cerebellar Purkinje neurons to extract small and large molecules from the cerebrospinal fluid has important implications for their physiology and pathology.

Animals↗
PubMed2002

A role for phosphorylation in the maintenance of resurgent sodium current in cerebellar purkinje neurons.

Cerebellar Purkinje neurons express voltage-gated, tetrodotoxin (TTX)-sensitive sodium channels that not only open and inactivate rapidly during depolarization but also reopen during repolarization, carrying an unusual "resurgent" sodium current. Expression of Na(V)1.6 alpha subunits appears necessary but not sufficient to generate this component of current; Purkinje cells without Na(V)1.6 lack resurgent current, but resurgent current is absent from many other Na(V)1.6-expressing neurons. These observations raise the question of how modulation or modification of the Na(V)1.6 subunit may lead to production of resurgent current. Previous studies have suggested that sodium channels of Purkinje neurons are subject to a rapid, voltage-dependent, open channel block by an endogenous particle whose unbinding allows resurgent current to flow. To investigate the nature of this block, we recorded TTX-sensitive sodium currents in outside-out patches from Purkinje cells acutely isolated from mice. In all patches, step depolarizations evoked transient current, and step repolarizations evoked resurgent current. The amplitudes of the transient and resurgent currents were highly correlated across patches (R(2) > 0.99), suggesting that the blocking agent is closely associated with the channel. Intracellular protease eliminated fast inactivation, indicating that the blocking element, like the fast inactivation gate, may be proteinaceous. Intracellular application of alkaline phosphatase abolished resurgent current and significantly slowed inactivation of transient current. The phosphatase inhibitor vanadate reduced these effects. Together, the results suggest that constitutive phosphorylation of the sodium channel complex of Purkinje neurons is necessary to maintain a functional blocking element and produce resurgent sodium current.

Alkaline Phosphatase↗
PubMed2003

Ionic mechanisms of burst firing in dissociated Purkinje neurons.

Cerebellar Purkinje neurons have intrinsic membrane properties that favor burst firing, seen not only during complex spikes elicited by climbing fiber input but also with direct electrical stimulation of cell bodies. We examined the ionic conductances that underlie all-or-none burst firing elicited in acutely dissociated mouse Purkinje neurons by short depolarizing current injections. Blocking voltage-dependent calcium entry by cadmium or replacement of external calcium by magnesium enhanced burst firing, but it was blocked by cobalt replacement of calcium, probably reflecting block of sodium channels. In voltage-clamp experiments, we used the burst waveform of each cell as a voltage command and used ionic substitutions and pharmacological manipulations to isolate tetrodotoxin (TTX)-sensitive sodium current, P-type and T-type calcium current, hyperpolarization-activated cation current (Ih), voltage-activated potassium current, large-conductance calcium-activated potassium current, and small-conductance calcium-activated potassium (SK) current. Measured near the middle of the first interspike interval, TTX-sensitive sodium current carried the largest inward current, and T-type calcium current was also substantial. Current through P-type channels was large immediately after a spike but decayed rapidly. These inward currents were opposed by substantial components of voltage-dependent and calcium-dependent potassium current. Termination of the burst is caused partly by decay of sodium current, together with a progressive buildup of SK current after the first interspike interval. Although burst firing depends on the net balance between multiple large currents flowing after a spike, it is surprisingly robust, probably reflecting complex interactions between the exact voltage waveform and voltage and calcium dependence of the various currents.

Action Potentials↗