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At least 19 recordsLinked to original sources
PubMed1991

Increased cell number in remaining cerebellar nuclei after cerebellar hemispherectomy in neonatal rats.

After cerebellar hemispherectomy before the 10th day of life aberrant cerebello-rubral projections develop from the nuclei in the remaining hemisphere, which terminate on the ipsilateral side. These aberrant fibres stem from separate parent cells in the lateral and interposed nuclei. The problem addressed by the present study was whether the number of neurones in these nuclei is increased after early cerebellar hemispherectomy. Results demonstrate that the number of neurones was increased by 50-60%. The volumes of the nuclei were also increased (14-31%) but much less so, which indicates a relative decrease in neuropil per neuron.

Animals↗
PubMed1994

Pharmacological characterization of somatostatin receptors in rat cerebellar nuclei.

Rat cerebellar nuclei contain somatotropin release-inhibiting factor (SRIF) receptors that bind [125I][Leu8,D-Trp22,Tyr25]SRIF-28 but do not bind [125I][Tyr0,D-Trp8]SRIF-14. The aim of the present study was to investigate the pharmacological profile of these receptors by means of binding experiments on tissue sections and quantitative autoradiography. Competition experiments indicated the presence of a single class of [125I][Leu8,D-Trp22,Tyr25]SRIF-28 binding sites in the lateral cerebellar nuclei, showing similar affinities for SRIF-14 and SRIF-28, but low affinity for short-chained analogs. The IC50 values for somatostatin analogs to compete with the binding of [125I][Leu8,D-Trp22,Tyr25]SRIF-28 in the lateral cerebellar nuclei ranked as follows: [Leu8,D-Trp22,Tyr25]SRIF-28 approximately SRIF-14 approximately SRIF-28 < CGP 23996 < D-Phe-Phe-Phe-D-Trp-Lys-Thr-Phe-Thr-NH2 (BIM 23052) < SMS 201-995 approximately N-Ahep-(7-10)SRIF-14-Bzl << MK 678 < D-Phe-Phe-Tyr-D-Trp-Lys-Val-Phe-D-Nal-NH2 (BIM 23056) < D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]Nal-NH2 (NC 8-12). Optimum binding of [125I][Leu8,D-Trp22,Tyr25]SRIF-28 did not require divalent cations, and was partly inhibited by guanosine 5' triphosphate. It appears from this study that the rat lateral cerebellar nuclei contain a pure population of receptors exhibiting the same binding characteristics as the recently cloned sstr1 somatostatin receptor. These nuclei could thus provide a useful model in which to investigate the characteristics of native sstr1.

Amino Acid Sequence↗
PubMed1987

Differential effects of serotonin on the spontaneous discharge and on the excitatory amino acid-induced responses of deep cerebellar nuclei neurons in rat cerebellar slices.

The effects of steady iontophoretic applications of serotonin on the spontaneous discharge and on the excitatory responses induced in deep cerebellar nuclei neurons by iontophoretic pulse applications of L-glutamate, L-aspartate, N-methyl-D,L-aspartate and quisqualate were studied in rat cerebellar slices maintained in vitro. Serotonin increased the spontaneous firing rate of deep cerebellar nuclei neurons in 91% of the tested cells by 109% on the average and had no effect on the remaining recorded neurons. Conversely, the monoamine induced a depression of the excitatory responses induced by four agonists tested and the depressant potency of serotonin was in the order quisqualate, glutamate, aspartate, N-methyl-D,L-aspartate. These effects persisted in low calcium high magnesium solution, suggesting that the serotonin receptors involved in these phenomena were, at least partially, postsynaptically located. The serotonin-induced increase in the cell firing rate appeared to be methysergide-resistant whereas the serotonin-induced decrease in the responses elicited by excitatory amino acids was depressed by this antagonist, which could indicate that these differential effects of serotonin are mediated via different mechanisms and/or serotonin receptor subtypes.

Action Potentials↗
PubMed1987

The projection of the nucleus reticularis tegmenti pontis and adjacent regions of the pontine nuclei to the central cerebellar nuclei in the cat.

The projection of the nucleus reticularis tegmenti pontis (NRTP) and the pontine nuclei (NP) to the central cerebellar nuclei (CCN) was investigated by means of anterograde transport of tritiated leucine. Although termination was found in all the CCN, it was most pronounced in the lateral nucleus and the lateral aspect of the posterior interposed nucleus. The extreme lateral aspect of the anterior interposed nucleus and the caudal part of the fastigial nucleus received a projection of modest intensity. Termination in the infracerebellar nucleus and group Y is likely to be present but could not be confirmed with certainty from the light microscopical material. The contribution from the NP was small and originated from the dorsolateral and dorsal paramedian subdivisions of the NP. Within the NRTP the total area giving rise to projections to the CCN was extensive, and the origin of the projections to the individual CCN overlapped considerably. The projection of the NRTP to the ventrocaudal part of the lateral nucleus was found in conjunction with a projection to the ventrolateral part of the posterior interposed nucleus. Both projections seemed to branch off the fiber bundle terminating in the ventral paraflocculus. Similar correlations could be established in the projection of the NRTP to the dorsal paraflocculus and crus II of the ansiform lobule with other parts of the lateral and posterior interposed nuclei. It was concluded that the transverse, lobular organization of mossy fibers, which differs fundamentally from the longitudinal, modular organization of climbing fibers, is maintained in the collateral projection to the CCN. The results are further discussed in relation to the corticonuclear projection and the engagement of the NRTP and different parts of the CCN in pontocerebellar circuits.

Animals↗
PubMed2000

The control of rate and timing of spikes in the deep cerebellar nuclei by inhibition.

Cerebellar nucleus neurons were recorded in vitro, and dynamic clamping was used to simulate inhibitory synaptic input from Purkinje cells likely to occur in vivo. Inhibitory input patterns with varying synaptic amplitudes and synchronicity were applied to determine how spike rate and spike timing can be controlled by inhibition. The excitatory input conductance was held constant to isolate the effect of dynamic inhibitory inputs on spiking. We found that the timing of individual spikes was controlled precisely by short decreases in the inhibitory conductance that were the consequence of synchronization between many inputs. The spike rate of nucleus neurons was controlled in a linear way by the rate of inhibitory inputs. The spike rate, however, also depended strongly on the amount of synchronicity present in the inhibitory inputs. An irregular spike train similar to in vivo data resulted from applied synaptic conductances when the conductance was large enough to overcome intrinsic pacemaker currents. In this situation subthreshold fluctuations in membrane potential closely followed the time course of the combined reversal potential of excitation and inhibition. This indicates that the net synaptic driving force for realistic input levels in vivo may be small and that synaptic input may operate primarily by shunting. The accurate temporal control of output spiking by inhibitory input that can be achieved in this way in the deep cerebellar nuclei may be particularly important to allow fine temporal control of movement via inhibitory output from cerebellar cortex.

Action Potentials↗
PubMed2006

Morphological and electrophysiological properties of GABAergic and non-GABAergic cells in the deep cerebellar nuclei.

The deep cerebellar nuclei (DCN) integrate inputs from the brain stem, the inferior olive, and the spinal cord with Purkinje cell output from cerebellar cortex and provide the major output of the cerebellum. Despite their crucial function in motor control and learning, the various populations of neurons in the DCN are poorly defined and characterized. Importantly, differences in electrophysiological properties between glutamatergic and GABAergic cells of the DCN have been largely elusive. Here, we used glutamate decarboxylase (GAD) 67-green fluorescent protein (GFP) knock-in mice to unambiguously identify GABAergic (GAD-positive) and non-GABAergic (GAD-negative, most likely glutamatergic) neurons of the DCN. Morphological analysis of DCN neurons patch-clamped with biocytin-containing electrodes revealed a significant overlap in the distributions of the soma sizes of GAD-positive and GAD-negative cells. Compared with GAD-negative DCN neurons, GAD-positive DCN neurons fire broader action potentials, display stronger frequency accommodation, and do not reach as high firing frequencies during depolarizing current injections. Furthermore, GAD-positive cells display slower spontaneous firing rates and have a more shallow frequency-to-current relationship than the GAD-negative cells but exhibit a longer-lasting rebound depolarization and associated spiking after a transient hyperpolarization. In contrast to the rather homogeneous population of GAD-positive cells, the GAD-negative cells were found to consist of two distinct populations as defined by cell size and electrophysiological features. We conclude that GABAergic DCN neurons are specialized to convey phasic spike rate information, whereas tonic spike rate is more faithfully relayed by the large non-GABAergic cells.

Action Potentials↗
PubMed2005

Change in diazepam sensitivity of GABAA currents after LTP induction in neurons of deep cerebellar nuclei.

In deep cerebellar nuclei (DCN) neurons, inhibitory postsynaptic currents (IPSCs) undergo long-term depression (LTD) following a 10-Hz stimulation, and long-term potentiation (LTP) after a 100 Hz stimulation of the inputs. Whole-cell recordings were made from DCN neurons and changes in IPSC sensitivity to diazepam after LTD and LTP investigated. Diazepam enhanced the evoked IPSC amplitude by 45% in controls and after LTD induction. However, after LTP induction, diazepam increased the IPSC by only 16%. Diazepam increased THIP response by 34% in controls, but by only 4% after LTP. These results suggest that during LTP the diazepam sensitive GABAA receptor sub-units undergo changes.

Animals↗
PubMed1999

Transient expression of somatostatin sst2 receptors in rat cerebellar nuclei during development.

Adult rat cerebellar nuclei contain a single population of [125I][Leu8,D-Trp22,Tyr25]somatostatin-28 binding sites characterized as sst1 receptors. In the present study, we have investigated the evolution of somatostatin receptors in rat cerebellar nuclei during development by means of quantitative autoradiography on tissue sections. The binding of [125I][Leu8,D-Trp22,Tyr25]somatostatin-28, observed in the primordium of the medial cerebellar nuclei at embryonic day 17, reached a maximum at postnatal day 7 or 10 in the different nuclei. Thereafter, the density of binding sites gradually decreased to the adult level. Competition studies were performed using the somatostatin analogues CH-288 and MK-678 as specific sst1 and sst2 ligands, respectively. Partial inhibition of the radioligand binding by CH-288 and MK-678 revealed the presence of a predominant population of sst1 from embryonic day 19-28 day postnatal and a minor population of sst2 receptors. The use of [125I]MK-678 as a radioligand confirmed the presence of a transient population of sst2 receptors, suggesting that somatostatin could act on rat cerebellar nuclei via sst1 and/or sst2 receptors during development.

Animals↗
PubMed1994

Olivary projecting neurons in the nucleus of Darkschewitsch in the cat receive excitatory monosynaptic input from the cerebellar nuclei.

The direct projection from the cerebellar nuclei to the inferior olive is GABAergic. In the present study, we investigated the projection from the cerebellar nuclei to the mesodiencephalic junction which is known to provide an excitatory projection to the inferior olive. The mesodiencephalic junction was studied in cat following anterograde transport of wheatgerm agglutinated horseradish peroxidase from the cerebellar nuclei in combination with: (1) retrograde transport of gold-lectin conjugate from the inferior olive; and (2) postembedding GABA-immunocytochemistry. Light microscopic analysis revealed that overlap of the anterograde and retrograde labeling was especially prominent in the nucleus of Darkschewitsch. Electron microscopic examination of this area showed: (1) that many cerebellar terminals made synaptic contacts with neurons that project to the inferior olive; (2) that virtually all cerebellar terminals were non-GABAergic and displayed an excitatory morphology; and (3) olivary projecting neurons were non-GABAergic. It is concluded that the indirect cerebellar projection to the inferior olive via the nucleus of Darkschewitsch is disynaptic and excitatory.

Animals↗
PubMed1985

Volume comparisons in the cerebellar complex of primates. II. Cerebellar nuclei.

Volumes of medial, interposed, and lateral cerebellar nuclei (MCN, ICN, and LCN) were measured in Insectivora, Scandentia, and Primates, including man. The relative size of the nuclei was expressed in size indices. Insectivora had by far the smallest cerebellar nuclei. The simians, in general, had larger cerebellar nuclei than the prosimians, but there was considerable overlap. From Insectivora to man, the MCN was the least progressive and the LCN the most progressive. The indices are expected to reflect the relative size of the three longitudinal zones of the cerebellum (vermis/MCN, pars intermedius/ICN, hemisphere/LCN). They, together with those of the ventral pons and cerebellum (part I), are discussed in relation to the predominant locomotor pattern of a species, and with reference to evolutionary trends in primate phylogeny.

Animals↗
PubMed1997

Climbing fibre collaterals contact neurons in the cerebellar nuclei that provide a GABAergic feedback to the inferior olive.

The inferior olive provides climbing fibres to Purkinje cells in the cerebellar cortex and gives off axon collaterals to the cerebellar nuclei. The cerebellar nuclei contain GABAergic neurons that provide an inhibitory projection to the inferior olive and excitatory neurons that influence behaviour through various other premotor nuclei in the brainstem and diencephalon. Whether the olivary axon collaterals innervate the GABAergic neurons in the cerebellar nuclei is unknown. In the present study we investigated this projection in mice at the ultrastructural level using post-embedding GABA immunocytochemistry and anterograde and retrograde tracing of biotinylated dextrane amine and gold-lectin. It is demonstrated that the olivary axon collaterals do not only innervate non-GABAergic neurons in the cerebellar nuclei, but also GABAergic nucleo-olivary cells, thus establishing a direct feedback loop to the inferior olive.

Animals↗
PubMed2002

Depression of inhibitory synaptic transmission between Purkinje cells and neurons of the cerebellar nuclei.

Neurons of the cerebellar nuclei have basal firing rates of 10-20 Hz, despite the convergence of many GABAergic Purkinje terminals onto cerebellar nuclear somata and the high spontaneous firing rate of Purkinje neurons. This persistence of firing during a constant barrage of inhibition raises the question of what patterns of Purkinje cell input inhibit nuclear cells most effectively. To explore the hypothesis that synaptic depression moderates inhibition at this synapse, we made whole-cell recordings from cerebellar nuclear neurons in mouse brain slices. IPSCs and IPSPs were elicited by electrically stimulating the corticonuclear tract at 10, 50, and 100 Hz. IPSCs evoked at the mean spontaneous firing rate of Purkinje cells (50 Hz) depressed by approximately 60%. The onset of depression had a fast, frequency-dependent component, from which recovery was rapid (approximately 100 msec), and a slower, frequency-independent component, from which recovery was slow (approximately 10 sec). As stimulation rate increased, steady-state depression increased, but each IPSC decayed less completely between stimuli, producing a "tonic" IPSC. Changes in stimulation rate produced rapid changes in the level of depression. Under current clamp, cerebellar nuclear neurons fired spontaneously. During 50 Hz trains of IPSPs, firing was initially interrupted, but resumed coincident with the onset of depression. Low-frequency trains entrained postsynaptic firing, and high-frequency trains greatly slowed firing, primarily because of the tonic IPSC. Thus, the properties of depression at this synapse appear to limit the sensitivity of nuclear cells to basal inhibition, while allowing the cells to respond to increases and decreases in Purkinje cell activity.

Animals↗
PubMed2000

Ionic currents and spontaneous firing in neurons isolated from the cerebellar nuclei.

Neurons of the cerebellar nuclei fire spontaneous action potentials both in vitro, with synaptic transmission blocked, and in vivo, in resting animals, despite ongoing inhibition from spontaneously active Purkinje neurons. We have studied the intrinsic currents of cerebellar nuclear neurons isolated from the mouse, with an interest in understanding how these currents generate spontaneous activity in the absence of synaptic input as well as how they allow firing to continue during basal levels of inhibition. Current-clamped isolated neurons fired regularly ( approximately 20 Hz), with shallow interspike hyperpolarizations (approximately -60 mV), much like neurons in more intact preparations. The spontaneous firing frequency lay in the middle of the dynamic range of the neurons and could be modulated up or down with small current injections. During step or action potential waveform voltage-clamp commands, the primary current active at interspike potentials was a tetrodotoxin-insensitive (TTX), cesium-insensitive, voltage-independent, cationic flux carried mainly by sodium ions. Although small, this cation current could depolarize neurons above threshold voltages. Voltage- and current-clamp recordings suggested a high level of inactivation of the TTX-sensitive transient sodium currents that supported action potentials. Blocking calcium currents terminated firing by preventing repolarization to normal interspike potentials, suggesting a significant role for K(Ca) currents. Potassium currents that flowed during action potential waveform voltage commands had high activation thresholds and were sensitive to 1 mm TEA. We propose that, after the decay of high-threshold potassium currents, the tonic cation current contributes strongly to the depolarization of neurons above threshold, thus maintaining the cycle of firing.

Action Potentials↗
PubMed1984

Cerebellar efferents in the lizard Varanus exanthematicus. II. Projections of the cerebellar nuclei.

The projections of the cerebellar nuclei have been studied in the lizard Varanus exanthematicus with various experimental anatomical techniques. In anterograde degeneration experiments (lesions of the cerebellar peduncle) both ascending and decending contralateral projections were found. Ascending fibers which could be traced from the cerebellar commissure ventralward decussated at the level of the trochlear and oculomotor nuclei. These fibers coursed rostralward to the mesodiencephalic junction. With anterograde tracing techniques (3H-leucine and HRP) this tract was found to terminate in the nucleus ruber and the interstitial nucleus of the fasciculus longitudinalis medialis. Moreover, retrograde tracer studies (HRP, "Fast Blue") showed that this tract appeared to arise mainly in the lateral cerebellar nucleus. With both anterograde degeneration and tracing techniques (3H-leucine and HRP) a bundle of fibers could be followed, which decussates in the basal part of the cerebellum and passes dorsally around the contralateral medial cerebellar nucleus to the lateral side of the brainstem. This contralaterally descending projection system was found, lateral to the vestibular nuclear complex, and as far caudally as the descending vestibular nucleus, to terminate on various vestibular nuclei. Horseradish peroxidase studies showed that this contralaterally descending projection system originates mainly in the medial cerebellar nucleus, but ipsilaterally descending projections were also found. With the fluorescent double labeling technique ("Fast Blue" and "Nuclear Yellow") the projections of the cerebellar nuclei described above were confirmed. Furthermore, double labeling revealed neurons in both cerebellar nuclei (especially the medial nucleus) that project to both the mesencephalon and the cervical spinal cord. The present results indicate that the efferent connections of the cerebellar nuclei in the lizard Varanus exanthematicus are organized as two main projections, an ascending projection comparable to the mammalian brachium conjunctivum arising in the lateral cerebellar nucleus, and a descending projection comparable to the mammalian hook bundle (fasciculus uncinatus), originating mainly in the medial cerebellar nucleus. Such projections are common for terrestrial vertebrates.

Animals↗
PubMedDate not supplied

GABA levels and GAD immunoreactivity in the deep cerebellar nuclei of rats with altered olivo-cerebellar function.

Immunocytochemistry was used to examine the distribution, size, and density of glutamic acid decarboxylase immunoreactive (GAD+) puncta in two animal models with movement disorders, the genetically dystonic (dt) rat and rats with 3-acetylpyridine (3AP) lesions of the inferior olive. In both models, GAD activity is increased in the deep cerebellar nuclei (DCN) where the enzyme is localized primarily in the terminals of Purkinje cells. GABA levels were also measured in the DCN. The general distribution of GAD+ puncta in the DCN was similar in all groups. Immediately after the 3AP lesions, however, GABA levels were elevated in 3AP rats in comparison with both normal rats and age-matched dt rats. GAD+ puncta were also larger than normal in the 3AP group at this time, although the magnitude of this effect declined over a 2-week recovery period. Puncta density was decreased in the medial nucleus only in 25-day-old dt rats in comparisons with normal littermates. These findings are discussed in the context of previously reported differences in the firing rate of Purkinje cells in dt and 3AP-treated rats.

Animals↗
PubMed1993

Long-term depression of IPSPs in rat deep cerebellar nuclei.

Stimulation of the white matter between the cerebellar cortex and the deep cerebellar nuclei in rat cerebellar slices, evoked inhibitory postsynaptic potentials (IPSPs) in deep nuclear neurones. These IPSPs had reversal potentials close to -75 mV and were blocked by picrotoxinin. Stable IPSPs were evoked when the white matter was stimulated at 0.033 Hz; however, at frequencies > 0.2 Hz, the synaptic transient was suppressed. Paired-pulse depression of the IPSP occurred at inter-pulse intervals of 100-400 ms. Subsequent to stimulation at 0.2-5 Hz, a short-term depression of the IPSP occurred while a tetanic stimulation at 100 Hz caused a long-term depression. These results indicate that IPSPs in the deep cerebellar nuclei undergo activity-mediated plasticity.

Animals↗
PubMed1996

Presynaptic GABAB receptors modulate IPSPs evoked in neurons of deep cerebellar nuclei in vitro.

1. Recording from deep cerebellar nuclei neurons, we investigated the role of presynaptic gamma-aminobutyric acid-B (GABAB) receptors in the modulation of monosynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of Purkinje cells in rat slice cultures. 2. Bath application of the GABAB receptor agonist, baclofen (10 and 100 microM) induced two effects in cerebellar nuclei neurons: a postsynaptic hyperpolarization of 4.2 +/- 1.7 (SD) mV and a reduction in the amplitude of evoked IPSPs (30 +/- 10%). 3. When the postsynaptic GABAB response was blocked by filling the electrode with cesium methanesulfonate (2 M), or with a solution containing QX 314 (50 mM), bath application of baclofen (10 microM) reversibly depressed the evoked IPSPs by 36.7 +/- 18.7% and 42 +/- 20.3%, respectively. Under these experimental conditions, baclofen (10 microM) also reduced the amplitude of spontaneous IPSPs (10.2 +/- 9.5%) and decreased their frequency by 45.6 +/- 8.8%, suggesting a presynaptic site of action. 4. The presynaptic action of baclofen was not due to activation of receptors on the somata of Purkinje cells: baclofen (100 microM) failed to alter membrane holding current in Purkinje cells, and it had no effect on the rate of spontaneous action-potential discharge in Purkinje cells in the presence of ionotropic glutamate receptor antagonists (6-cyano-7-nitroquinoxaline-2,3-dione, 20 microM; D-2-amino-5-phosphonovalerate, 40 microM). 5. IPSPs could be evoked by extracellular stimulation of the Purkinje cell layer or by direct stimulation of the fiber bundle connecting Purkinje cells to deep cerebellar neurons. In both situations, baclofen (10 microM) reduced the amplitude of evoked IPSPs by 32.7 +/- 8.8% and 31.2 +/- 10.2%, respectively. 6. These results demonstrate that GABAB receptors are present on the terminals of Purkinje cells. Their activation causes a decrease in the amplitude of evoked IPSPs recorded in deep cerebellar nuclei and also reduces the frequency of spontaneous inhibitory events.

Animals↗