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PubMed1979

[Possibility of using an analgesic (fentanyl) for electrophysiologic studies of the cerebellar cortex].

The effect of the central analgetic, fentanyl, on evoked potentials and Purkinje cells discharges in the cerbellar cortex to stimulation either the cerebral cortex or somatic nerves were studied in nonanaesthetized cats. It was found that the analgetic dose fentanyl (10-30 microgram/kg) did not affect the evoked potentials. The fentanyl dose of 30 microgram/kg suppressed the resting discharges and responses of Purkinje cells while the dose of 10 microgram/kg facilitated them. However these effects were substantially weaker as compared with those of nembutal. Therefore fentanyl can be used for analgesia during electrophysiological study of the cerebellar cortex in nonanaesthetized cats.

Animals↗
PubMed2005

Simple spike firing in the posterior lateral cerebellar cortex of Macaque Mulatta was correlated with success-failure during a visually guided reaching task.

Evidence has been accumulating which supports a role for the cerebellum in motor learning. Motor learning is though to be mediated by complex spikes acting as an error signal, which when firing in conjunction with simple spike activity modify synapses between parallel fibers and Purkinje cells. We studied the activity of neurons in the posterior lateral cerebellar cortex of macaques that were performing reaches to visual targets. We found that simple spike firing in many of these neurons was modulated by whether the monkey successfully hit the target or not. The success-failure modulation was present for reaches using either arm and could persist for several hundred milliseconds into a period when the monkey was constrained from moving its arms. This temporally extended success-failure activity could interact with complex spike firing in order to enhance learning, particularly when the motor command is temporally separated from sensory feedback.

Animals↗
PubMed1979

[Spatial organization of inhibitory control of the activity of the vestibulospinal neurons of Deiter's nucleus by the Purkinje cells in the anterior lobe of the cerebellar cortex].

Peculiarities of topographical distribution of the Deiters nucleus vestibulospinal neurons were studied by means of microelectrode technique. It is shown, in contrast to morphological data, that the localization of antidromically identified vestibulocervical (C-neurons) and vestibulolumbal (L-neurons) cells is not restricted to the ventral mid- and rostral third part (forelimb region) and caudosorsal part (hindlimb region) of the nucleus, but extends correspondingly to the whole ventral and dorsal halves of the nucleus. There is a great overlapping in zones of these two groups of neurons: C-neurons are found in the dorsal portion also, whereas L-neurons--in its ventrocaudal part. Analysis of distribution of monosynaptic IPSPs in the vestibulospinal neurons, evoked in response to the stimulation of the Purkinje cells, has shown that the C-neurons are controlled mainly from the forelimb region of the cerebellar cortex, whereas L-neurons are inhibited from the forelimb as well as from the hindlimb regions of the vermal cortex anterior lobe.

Action Potentials↗
PubMed1987

Collateral projections from trigeminal sensory nuclei to ventrobasal thalamus and cerebellar cortex in rats.

The retrograde fluorescent labeling technique reveals that trigeminal projections to the ventroposteromedial nucleus of the thalamus (VPM) of the rat originate from the main sensory nucleus (MSN) of the trigeminal and subnuclei interpolaris (V1) and caudalis (Vc) of the spinal trigeminal nucleus. These projections are predominantly contralateral; however, the presence of a few ipsilateral labeled cells in MSN suggests an uncrossed trigeminothalamic pathway. Trigeminocerebellar fibers projecting to the paramedian lobule (PML) of the cerebellar cortex are located in Vi and caudal subnucleus oralis (Vo). This is principally an ipsilateral pathway, but several bisbenzimide-labeled cells are present in contralateral Vi. The most notable finding occurred after paired injections of Evans Blue into VPM and bisbenzimide into PML, demonstrating neurons in Vi with divergent projections to both structures. The presence of this type of projection was not found in mice (Steindler: J. Comp. Neurol. 237:155-175, 1985) and has not been reported in other species.

Afferent Pathways↗
PubMed1992

Regressional changes of human cerebellar cortex and hypoglossal nucleus during development.

In the development of nervous system, two processes are of a particular interest. It is well known that after a primary migration of cells, there appears a consecutive regression in cellular number, closely connected with the maturation of the nervous system. The dynamics of this reduction was investigated following the changes in number of cells in nucleus hypoglossus as well as that of Purkinje cells in two structures of cerebellar cortex--in vermis and in hemispheres. Cell nuclei were counted using the stereological technique, after a usual preparation. Data were collected from 20 human brains of different gestation age, i.e. at 12.5, 14, 17.5, 19.5, 24, 31, weeks of gestation and 6 day old newborn. After the graphical and numerical analysis of the data obtained, an adequate mathematical model was proposed. It is confirmed that a close agreement between biological data and decreasing two-exponential equation can be demonstrated, pointing out that the cellular reduction shows a proportional relation. The possible explanation could be that only the cells forming proper and useful connections and entering the informational system have a privilege to survive, and that all improper contacts lead to the rejection of cells or even of groups of cells.

Cerebellar Cortex↗
PubMed2001

[Level of nerve growth factor protein in cerebellar cortex of rat pups in intrauterine growth retardation model by clamping the uterine vasculature of pregnant rat].

OBJECTIVE: To understand the level of nerve growth factor (NGF) in the brain of rat pups in intrauterine growth retardation (IUGR), explore the mechanism of brain injury. METHODS: Animal models for IUGR pups were established by clamping the uterine vasculature of pregnant rats with 30 minutes in this study. NGF proteins were measured by immunohistochemistry in the cerebellar cortex of rat pups at birth (21 days of gestation), and on the sixth day after birth. RESULTS: 1. The body weight of the 21-day fetuses in IUGR group decreased 16.1% as compared to that in control group (P < 0.0001); 2. The brain weight of the 21-day fetuses in IUGR group decreased to that in control group (P < 0.05) development of their brain retardation during the intrauterine in IUGR fetus period in this model; 3. On the sixth day after birth, there was no statistical difference in body weight between the IUGR and the control groups. But the brain weight difference between these two groups was still there; 4. At birth and on the sixth day after birth, there were statistical differences in NGF proteins in cerebellum between the IUGR and the control groups, which got along with the decrease of their brain weights. CONCLUSION: A successful animal model of IUGR was established by clamping the uterine vasculature of pregnant rats with 30 minutes, and the development of their brain were retarded in IUGR fetus period in this model. Brain retardation in IUGR pups may relate with the decreased level of NGF in brain. This study discovered that quick "catch-up" growth in physical development and slow "catch-up" growth in brain development in IUGR pups.

Animals↗
PubMed2005

Kappa opioid receptor is expressed in the rat cerebellar cortex.

Classically, the cerebellum has been shown to be involved in motor and visual functions, although recent evidence point to new roles of this organ. Pain processing is one of the recently described functions of the cerebellum. According to the importance of the opioid system in nociception, a detailed characterization of the expression pattern of opioid peptides in the cerebellum is the first step towards understanding the precise involvement of this organ in pain management. By using two different approaches (reverse transcription/polymerase chain reaction and in situ hybridization), we have detected, for the first time, expression of the kappa opioid receptor (KOR) gene in the cerebellar cortex of the rat. Expression is found in the molecular and granular layers in all the lobules of the cerebellum. Approximately 34% of the cells present in the molecular layer express KOR mRNA. This work contributes to the deeper knowledge of the mechanisms that are involved in cerebellar function and may lead to a better understanding of the relationships between nociceptive activity and drug abuse potential.

Animals↗
PubMed2000

Chronic methamphetamine exposure decreases high affinity uptake function in norepinephrine afferents in the cerebellar cortex: an electrophysiological and electrochemical study.

It has been reported that chronic methamphetamine (MA) treatment decreases monoamine release in different brain regions. However, the clearance of norepinephrine (NE) after chronic MA intake is not clear. In the present study, we administered MA to Sprague-Dawley rats for 1 month. The animals were later anesthetized with urethane for electrophysiological recording. Previous studies have indicated that gamma-aminobutyric acid (GABA)-induced electrophysiological responses are enhanced by norepinephrine (NE) acting via postsynaptic beta-adrenergic receptors. We found that local application of the NE high affinity uptake inhibitor desmethylimipramine (DMI) significantly potentiated GABA-induced electrophysiological depressions in cerebellar Purkinje neurons in control rats. In contrast, DMI did not augment GABA responses in rats chronically treated with MA for 1 month, or in rats withdrawn from MA for 7-14 days after a 1-month MA treatment. To further examine if DMI-induced GABA modulation is altered by post- or pre-synaptic mechanisms in chronic MA-treated rats, we examined the electrophysiological interaction of GABA and isoproterenol (ISO), a postsynaptic beta-adrenergic receptor agonist, in Purkinje neurons. We found that GABA-induced inhibition is potentiated by local application of ISO in both control and chronic MA rats, suggesting that the reduction in DMI/GABA interactions is probably not mediated through post-synaptic noradrenergic mechanisms. Presynaptic NE clearance was further examined using in vivo chronoamperometric methods. Extracellular NE levels in the cerebellar cortex were measured using Nafion-coated carbon fiber sensors. We found that local application of DMI inhibited NE clearance in control rats, but not in chronic MA animals, suggesting that presynaptic NE clearance is reduced after chronic MA treatment. In addition, NE levels in cerebellar tissue were measured using HPLC-ECD. The NE concentration was significantly decreased in chronic MA rats. Taken together, our data suggest that regulation of uptake by DMI at central noradrenergic nerve terminals is abnormal after chronic MA exposure.

Action Potentials↗
PubMed1976

Experimental reorganization of the cerebellar cortex. VII. Effects of late x-irradiation schedules that interfere with cell acquisition after stellate cells are formed.

In Long-Evans rats the area of the cerebellum was irradiated with multiple doses of low-level X-ray beginning on day 12 after the bulk of stellate cells were acquired. The treatment spared basket, stellate and early-forming granule cells but led to a substantial reduction in the total granule cell population and a correlated miniaturization of the cerebellar cortex. Nevertheless most Purkinje cells had normally shaped planar dendritic arbors, with an upward directed stem dendrite, several smooth branches and a multitude of spiny branchlets. The frequency piling up of spiny branchlets near the surface was attributed to the truncation of the bed of parallel fibers by this radiation schedule. In this last paper of the series the accumulated results are summarized and evaluated. The hypothesis is offered that while the growth of the Purkinje cell perikaryon is an autonomous process, the oriented perpendicular growth of a single stem dendrite depends on the presence of basket cell axons, the outgrowth of smooth branches on the presence of stellate cell axons, and the proliferation of spiny branchlets on interaction with parallel fibers. The parallel fibers are responsible for the orthogonal, planar growth of the dendritic arbor and a hypothesis is offered about the mechanisms involved.

Animals↗
PubMed1983

Evidence for synaptic plasticity in the cerebellar cortex.

The learning machine model of the cerebellum by Marr and Albus contains a special type of synaptic plasticity. Experimental evidence for this synaptic plasticity has been meager, but very recently positive evidence has become available. Ito, Sakurai and Tongroach (7) demonstrated the occurrence of a long-lasting depression in mossy fiber responsiveness of Purkinje cells subsequent to conjuctive stimulation of mossy fibers and climbing fibers. A similar long-lasting depression was shown to occurred in sensitivity of Purkinje cell dendrites to a putative neurotransmitter of parallel fibers, i.e., glutamate. Furthermore, Ito and Kano (6) produced a long-lasting depression in the molecular layer of the cerebellar cortex by simultaneous direct stimulation of parallel fibers and climbing fibers. These long-lasting depressions appear to represent a synaptic plasticity of the form proposed by Albus.

Animals↗
PubMed1988

The effect of lesions of cerebellar cortex on retention of the classically conditioned eyeblink response when stimulation of the lateral reticular nucleus is used as the conditioned stimulus.

Ten male albino rabbits were implanted with stimulating electrodes in the lateral reticular nucleus (LRN). These rabbits were given paired classical conditioning training of the nictitating membrane response with stimulation of the LRN as the conditioned stimulus (CS) Each rabbit was given daily training sessions until it consistently made conditioned responses (CRs). Each rabbit then received an aspiration lesion of cerebellar cortex; the ipsilateral anso-paramedian lobule (n = 6), the anterior or central vermis (n = 2), the central vermis and ansiform lobule (n = 1), or the central vermis and paramedian lobule (n = 1). After recovery, these rabbits were again given paired classical conditioning training with LRN stimulation as the CS. The rabbits with anso-paramedian lesions did not retain the CR after the lesion, but were able to relearn it. The rabbits with lesions of the vermis, the vermis and ansiform, or the vermis and paramedian retained the CR after the lesion. These results are contrasted with previous results, which show that after aspiration of the anso-paramedian lobule, the conditioned response is not retained or relearned when stimulation of the dorsolateral pontine nucleus (DLPN) is used as a CS. The differences between the mossy fiber outputs of the LRN and DLPN may account for this discrepancy. Different regions of the cerebellum are apparently involved in retention of classically conditioned responses depending on the population of mossy fibers carrying the CS information.

Animals↗
PubMed2005

Transgenic mouse lines expressing synaptopHluorin in hippocampus and cerebellar cortex.

We generated six transgenic mouse lines in which synaptopHluorin (SpH), one of green fluorescent protein-based sensors of vesicular exocytosis, was expressed under the control of neuron-specific Thy-1.2 promoter. In situ hybridization study revealed that SpH mRNA was expressed in a broad spectrum of brain regions in four of them, whereas in others it was expressed in the specific regions of the hippocampus. In one particular line, SpH immunoreactivity was specifically observed in the mossy fiber presynaptic terminals of both hippocampus and cerebellar cortex. The fluorescence intensity of these presynaptic terminals was somewhat decreased by acidic buffer superfusion and greatly increased by vesicular neutralization of pH, indicating that the SpH molecules are mainly distributed in the synaptic vesicles. The exocytosis-dependent fluorescence increment was measured upon activation of a single presynaptic terminal. These transgenic lines are expected to facilitate morphological and physiological studies of presynaptic terminals in a variety of regions of the brain.

Animals↗
PubMed2003

Localization of the O-GlcNAc transferase and O-GlcNAc-modified proteins in rat cerebellar cortex.

O-linked N-acetylglucosamine (O-GlcNAc) is a ubiquitous nucleocytoplasmic protein modification that has a complex interplay with phosphorylation on cytoskeletal proteins, signaling proteins and transcription factors. O-GlcNAc is essential for life at the single cell level, and much indirect evidence suggests it plays an important role in nerve cell biology and neurodegenerative disease. Here we show the localization of O-GlcNAc Transferase (OGTase) mRNA, OGTase protein, and O-GlcNAc-modified proteins in the rat cerebellar cortex. The sites of OGTase mRNA expression were determined by in situ hybridization histochemistry. Intense hybridization signals were present in neurons, especially in the Purkinje cells. Fluorescent-tagged antibody against OGTase stained almost all of the neurons with especially intense reactivity in Purkinje cells, within which the nucleus, perikaryon, and dendrites were most intensely stained. Using immuno-electron microscopic labeling, OGTase was seen to be enriched in euchromatin, in the cytoplasmic matrix, at the nerve terminal, and around microtubules in dendrites. In nerve terminals, immuno-gold labeling was observed around synaptic vesicles, with the enzyme more densely localized in the presynaptic terminals than in the postsynaptic ones. Using an antibody to O-GlcNAc, we found the sugar localizations reflected results seen for OGTase. Collectively, these data support hypothesized roles for O-GlcNAc in key processes of brain cells, including the regulation of transcription, synaptic vesicle secretion, transport, and signal transduction. Thus, by modulating the phosphorylation or protein associations of key regulatory and cytoskeletal proteins, O-GlcNAc is likely important to many functions of the cerebellum.

Acetylglucosamine↗
PubMed1996

Reduction of CAG expansions in cerebellar cortex and spinal cord of DRPLA.

Recent studies have identified an unstable expansion of a CAG repeat in a gene located on chromosome 12 as a cause of dentatorubropallidoluysian atrophy (DRPLA). To investigate whether the somatic heterogeneity may relate to the selective neuronal damage caused by the disease, genomic DNA from various tissues of an autopsied patient with DRPLA was examined to compare possible variations of expanded CAG repeats for the disease. Although the size of the expanded CAG repeat from many organs was almost the same as that from peripheral lymphocytes, those from cerebellar cortex and spinal cord were unexpectedly reduced and numbers of peaks within an expanded allele were relatively strict. These results suggest that the CAG repeat is not simply expanded in the genome of the tissues that are most involved in DRPLA, but that another mechanism might be responsible for the specific neuronal death.

Adult↗
PubMed1996

Do microglia arise from pericytes? An ultrastructural and distribution study in the rat cerebellar cortex.

Both pericytes and microglia are dark cells that may present similar ultrastructure as well as organization of the rough endoplasmic reticulum cisternae; in addition, images that suggest pericytes being released from the basal lamina compartment, some of them looking like forms of perivascular microglia, may be found. Anatomical articulations between pericytes and microglia are observed. A distribution analysis reveals that, in the considered five neocerebellar cortical strata, the percentage of pericytes preponderates over the percentage of microglia; furthermore, there is a highly statistically significant linear trend between the percentages of pericytes and of microglia in connection with their distribution along the cortical strata. This study suggests that, in rat cerebellar cortex, microglia may arise from pericytes. It is also hypothesized that astroglia have an active role in releasing pericytes from the vascular wall.

Animals↗
PubMed1994

Effects of inhibition of the GABAergic systems by picrotoxin on retention of a nociceptive experience in the rat, with special reference to the influence of cerebellar cortex output.

Adult cerebellectomized and noncerebellectomized DA/HAN strain (pigmented) female rats were submitted to a one-trial passive avoidance conditioning procedure consisting in associating darkness with a nociceptive stimulus. Seven days later, they were tested again to assess the retention stage. The results demonstrate that in noncerebellectomized rats, picrotoxin, whatever the dose, administered prior to the retention test, does not significantly impair retrieval. On the contrary, when administered just prior to the initial conditioning, impairments of the initial single nociceptive experience were evident (the greater the picrotoxin dose, the greater the impairments). In animals that were cerebellectomized 1 week before the experiment, picrotoxin administered at a low dose before the initial experience elicited memory impairments that were similar to those induced in noncerebellectomized rats but that were greater than those elicited in cerebellectomized, nontreated animals. However, in cerebellectomized rats, picrotoxin administered at a low dose elicited memory impairments that were weaker than in noncerebellectomized animals injected with a high dose of the drug. Considering that a low dose of picrotoxin administered to cerebellectomized animals had effects that were similar to those of a high dose injected to noncerebellectomized rats, and given that it has previously been demonstrated that a cerebellectomy performed after a single nociceptive experience impairs its memory, it is tempting to suggest that the two different doses of the drug administered to cerebellectomized and noncerebellectomized rats have similar effects on memory. If such an interpretation is valid, the information would have to leave the cerebellar cortex to be stored for long.

Animals↗