Cerebellum Tonic Inhibition

Cross references:    Cerebellum    Deep Cerebellar Nuclei   
Cerebellar Afferent Pathways      Cerebellar Efferent Pathways     
Tonic Inhibition   
 
Searching PubMed for "cerebellum tonic inhibition" revealed 170 references:   
https://www.ncbi.nlm.nih.gov/pubmed/?term=cerebellum+tonic+inhibition  

1976    168<170       
Chronic cerebellar stimulation in epilepsy. Clinical and anatomical studies.   
https://www.ncbi.nlm.nih.gov/pubmed/821458   
    "Ten of 15 patients subjected to chronic cerebellar stimulation have had previously intractable seizures modified or inhibited up to periods of three years. Stimulation of anterior lobe appears to be more efficacious than stimulation of posterior lobe.  
    Cerebellar biopsies, obtained in five patients at the time of stimulator placement, revealed in every instance a reduction in the molecular layer, decreased or absent Purkinje cells, and decreased stellate cells. One unimproved patient died during a seizure 17 months after stimulation was initiated. Histological examination of the brain did not reveal tissue damage attributable to the stimulator. There is no evidence of any adverse effect of chronic cerebellar stimulation in humans who have undergone stimulation for periods up to three years."    

    My comment
    Electrical stimulation only.  No indication of the identity of the neurotransmitters.  


1977    167<170  
[Effects of electric stimulation of the dentate nucleus of the cerebellum on neuronal activity of the centrum medianum of the optic thalamus].   
https://www.ncbi.nlm.nih.gov/pubmed/881057   
    "Electrical stimulation of the cerebellar dentate nucleus elicits in neurons of the center median responses with either constant or altering latencies. The constant latencies ranged from 2-3 to 8-12 msec. Responses with altering latencies were more numerous and had the latencies up to 20 msec. In both responses with early and late components were recorded as well.  
    Dentate stimulations induced "periods of inhibition" in CM neurons with leading duration of 50-100 msec. Synchronization of the SM unit activity during low-frequency stimulation was also revealed, in many cases it was preceded by the "periods of inhibition". Activity of 49% of reactive neurons during 1, 7-12, and 70-100/sec stimulations was facilitated, 31% depressed, and 20% had a mixed type of responses: facilitation on one frequency and depression on another.  
     Immediate cessation of the effects after termination of stimulations was observed in 34% of neurons, while tonic influences were manifest in 66%."  

    My comment
    Electrical stimulation only.  No indication of any of neurotransmitters.  


1978    164<170 
The ventral spino-olivocerebellar system in the cat. V. Supraspinal control of spinal transmission.  
https://www.ncbi.nlm.nih.gov/pubmed/215435  
    "1. The transmission from the flexor reflex afferents (FRA) and from tracts running in the ipsilateral half of the spinal cord to the spino-olivocerebellar paths ascending through the ventral funiculus (VF-SOCPs) was compared with the transmission from these sources to segmental reflex arcs. The climbing fibre responses evoked in Purkinje cells by electrical stimulation of limb nerves and spinal tracts were monitored by recording the mass activity at the cerebellar surface simultaneously from several termination zones, while the activity in flexor motoneurones was recorded from a flexor nerve and the primary afferent depolarization from a dorsal filament. 
     2. Changes in the segmental reflex response were produced by release from the tonic inhibition of transmission from the FRA in decerebrate preparations and by conditioning electrical stimulation of dissected spinal funiculi containing inhibitory descending tracts.  
    3. The changes of the transmission from the FRA to two of the paths, the a- and b2-VF-SOCPs, parallelled the changes of the transmission to the segmental reflex arcs. On the other hand, the monosynaptic transmission from the FRA to the c1- and c3-VF-SOCPs was not significantly influenced by the inhibitory descending control systems.  
    4. The a- and b2-VF-SOCPs but not the c1- and c3-VF-SOCPs received polysynaptic excitation from tracts running in the ipsilateral half of the spinal cord.  
    5. The suggestion that the a- and b2-VF-SOCPs carry information related to interneuronal activity in segmental centres, whereas the c1- and c3-VF-SOCPs forward information mainly related to peripheral events is supported by the present findings."  

    My comment
    Electrical stimulation only.  No indication of identity of any of the neurotransmitters.  


1980    162<170 
Potentiation of GABA inhibitory action in cerebrllum by locus coeruleus stimulation. 
https://www.ncbi.nlm.nih.gov/pubmed/7357389  
    "In cerebellum, excitatory and inhibitory responses of Purkinje cells, produced both synaptically and by microiontophoresis of putative amino acid neurotransmitters, have been shown previously to be enhanced during NE iontophoresis. The influence of locus coeruleus conditioning stimulation on Purkinje cell responses to GABA iontophoresis was examined to determine whether endogenous NE, released from synaptic terminals, could exert similar modulatory effects.  
    Locus coeruleus stimulation at current intensities which alone elicited no direct depression of Purkinje cell spontaneous discharge potentiated the inhibition produced by GABA. Iontophoretic application of sotalol, a specific beta-adrenergic blocker, antagonized this enhancement of GABA inhibition. Repetitive activation of the classic non-adrenergic cerebellar afferents did not enhance the GABA response, despite causing a direct depression in spontaneous rate.  
    A neuromodulatory role is suggested for tonic adrenergic input in the mammalian central nervous system."  
    My comments:   
1.  Is the "tonic adrenergic input" related to Tonic Inhibition ?   If so, in what way?   
2.  Whether it's excitatory or inhibitory, this clearly implies that it's tonic.   
3.  Is the overall effect of  "Purkinje cell spontaneous discharge" excitatory or inhibitory? 


1980    161<170   
Mossy fiber projections to the cerebellar flocculus from the extraocular muscle afferents. 
https://www.ncbi.nlm.nih.gov/pubmed/7378763  
    See:  Cerebellar Afferent Pathways
 

1981    160<170   
Decerebrate rigidity in animals.   
https://www.ncbi.nlm.nih.gov/pubmed/6456428      
    "Decerebrate rigidity (DR) in animals is caused by a release of spinal neurons from supraspinal inhibition, which results in a caricature of reflex standing and includes tonic neck and labyrinthine reflexes. The reticular formation, cerebellum, vestibular complex, spinal cord, and muscle spindle system and their neurophysiological interaction are critical to DR. Its discovery and investigation were essential to Sherrington's concept of the integrative action of the nervous system. There are two types of DR with different anatomical and physiological bases.  
    Intercollicular decerebration yields rigidity in extensor muscles that results from bilateral destruction of the central tegmental tracts, is abolished by posterior root section, and is due to a facilitation of gamma motoneuron discharge (gamma animal).  
    Anemic decerebration is characterized by excessive extensor rigidity, depends upon the release of tonic labryinthine reflexes from cerebellar inhibition, is independent of posterior root section, and is caused by excessive alpha motoneuron discharge (alpha animal). 
     DR has provided an insight into the mechanisms of posture and standing, but the correlation of laboratory observations and results from animals to humans must be made with caution."  
    My comment
Although decerebrate rigidity is an example of tonic inhibition, I don't see a direct relationship between it and "normal" tonic inhibition. 


1982    158<170 
Functional aspects of the inferior olive. 
https://www.ncbi.nlm.nih.gov/pubmed/6753783  
    "A review is presented of a series of recent experiments aimed at studying the effects of irreversible lesion and of reversible inactivation of the inferior olive.  
    Following a permanent lesion of the inferior olive, no alteration has been found:  
        i) in the morphology of the synapse between Purkinje and Deiters neurones, and  
        ii) in the inhibitory properties of the three types of cells of the cerebellar cortex innervated by the olivocerebellar pathway: the Purkinje, the Golgi and the basket cells.  
    Following reversible inactivation of the inferior olive of one side by cooling, a remarkable increase of the simple spike activity has been found in all the Purkinje cells showing a disappearance of the climbing fibre activity. This effect is likely mediated, at a large extent, by climbing fibre collaterals through corticocerebellar interneurones. The same reversible inactivation of the inferior olive induces a drastic reduction of the activity in the cells of intracerebellar and vestibular nuclei.  
    These experiments don't provide support for a trophic function of the inferior olive on its target neurones. They suggest that this nucleus exerts a very powerful tonic inhibitory action on Purkinje cells and consequently a control on the excitability of intracerebellar and subcerebellar centres. Such a control is likely important for the processing of informations through the cerebellum and therefore for the control of motor activities."  
    My comments
1.  This implies that Purkinje, Golgi and basket cells comprise the "olivocerebellar pathway" and are inhibitory. 
2.  These experiments ... suggest that the inferior olive ... exerts a very powerful tonic inhibitory action on Purkinje cells and consequently a control on the excitability of intracerebellar and subcerebellar centres. 
    Important
3.  If Purkinje cells and the inferior olive are both inhibitory, then the overall affect of Purkinjie cells is excitatory. 


1982    157<170   
The inhibitory effect of the olivocerebellar input on the cerebellar Purkinje cells in the rat. 
https://www.ncbi.nlm.nih.gov/pubmed/7153927   
  Abstract
    "1. In rats under Nembutal anaesthesia the inferior olive region has been reversibly inactivated by applying a cooling probe to the ventral surface of the medulla. Simple and complex spike activity has been recorded from Purkinje cells of the cerebellar cortex.   
    2. Following cooling of the inferior olive of one side we have observed a remarkable increase of the simple spike activity in all the twenty-two Purkinje cells, showing a disappearance of the complex spike activity. 
    3. In some rats two Purkinje cells were recorded simultaneously from each side of the cerebellar cortex. Following cooling of the left inferior olive the effect on the Purkinje cell was observed only or predominantly on the contralateral cerebellar cortex 
    4. In a group of animals the inferior olive has been destroyed by 3-acetylpyridine 4-221 days before the recording session. Cooling of the inferior olive region was not accompanied by any significant and consistent increase in the spike activity of presumed Purkinje cells of the contralateral cerebellar cortex. 
    5. These results indicate that the remarkable increase of the simple spike frequency following cooling of the inferior olive region is due specifically to the suppression of the activity of the olivocerebellar neurones. 
    6. Only a small amount of the simple spike frequency increase is attributable to the removal of the post-climbing fibre pause. 
    7. In some lesioned rats recording was made from Purkinje cells, which showed complex spikes due to the few surviving inferior olive cells. In these Purkinje cells cooling of the inferior olive region was accompanied by a disappearance of the complex spike and by a small increase of the simple spike frequency of discharge. Such an increase is mainly attributable to the removal of the post-climbing fibre pause 
    8. These results suggest that a given Purkinje cell is not only under the inhibitory influence of its own climbing fibre, but also of other olivocerebellar neurones, probably through climbing fibre collaterals to the cerebellar cortical interneurones 
    9. It is suggested that one role of the olivocerebellar system is to exert a powerful tonic inhibitory action on the Purkinje cells and consequently to exert a significant control on the excitability of the subcerebellar centres." 
    My comments
    1.  The inferior olive region is reversibly inactivated by applying a cooling probe.  
    2.  Cooling the inferior olive causes the Perkinje cells to increase their simple spike activity and reduce their complex spike activity. 
    3.  The change in spike activity is contralateral to the cooling.   
    4.  This seems to imply that "simple and complex spike activity" oppose one another. 
    5.  ...  the inferior olive has been destroyed ... cooling of the inferior olive region was not accompanied by any significant and consistent increase 
    6.  ... increase of the simple spike frequency following cooling of the inferior olive region is due specifically to the suppression of the activity of the olivocerebellar neurones.
    7.  Purkinje cell is ... under the inhibitory influence
    8.  ... one role of the olivocerebellar system is to exert a powerful tonic inhibitory action on the Purkinje cells and consequently to exert a significant control on the excitability of the subcerebellar centres.   
     Free PMC Article  


1985     152<170 
On the Purkinje cell activity increase induced by suppression of inferior olive activity. 
https://www.ncbi.nlm.nih.gov/pubmed/2984036   
    "Previous experiments performed in rats under barbiturate anaesthesia have shown a remarkable increase of simple spike firing rate in cerebellar Purkinje cells following inferior olive lesion or inactivation. The increase is due, at least in part, to the withdrawal of the tonic background activity of corticocerebellar interneurones, which have GABA as a chemical transmitter. Since barbiturates potentiate GABAergic inhibition, it is possible that the effect is due to the presence of this type of anaesthesia. 
     In absence of general anaesthesia, we have compared the simple spike firing rate of the Purkinje cells in rats with intact inferior olive and 3-5 days after inferior olive lesion by 3-acetylpyridine. In the latter condition, the firing rate is significantly higher. In other rats, under urethane anaesthesia, which is not known to interfere with GABAergic transmission, the inferior olive has been reversibly inactivated by applying a cooling probe to the ventral surface of the medulla. Following cooling of the inferior olive on one side, a remarkable increase of simple spike activity, parallel to the disappearance of complex spike activity, has been observed in the Purkinje cells of the contralateral side.  
    These results show that the presence of the simple spike firing increase, which follows the removal of the climbing fibre activity, does not depend on an anaesthetic which potentiates GABAergic transmission, although its amplitude is affected by the same anaesthetic. They suggest, therefore, that the tonic inhibition exerted by the olivocerebellar pathway on the Purkinje cells operates also in physiological conditions."  
    My comment:   
"...
tonic background activity of corticocerebellar interneurones, which have GABA as a chemical transmitter "
"... the tonic inhibition exerted by the olivocerebellar pathway on the Purkinje cells  ..."  


1996 126<170
Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resulting from persistent activation of GABAA receptors.  
    "1. To investigate the origin and functional significance of a recently described tonic GABAA receptor-mediated conductance in cerebellar granule cells we have made recordings from cells in cerebellar slices from rats of different ages (postnatal days P4 to P28).  
    2. During development there was a dramatic change in the properties of GABA-mediated synaptic transmission. The contribution to GABAA receptor-mediated charge transfer from the tonic conductance (GGABA), relative to that resulting from discrete spontaneous postsynaptic currents (sPSCs), was increased from 5% at P7 to 99% at P21.  GGABA was reduced by bicuculline, tetrodotoxin and by lowering extracellular Ca2+, and was initially present only in those cells which exhibited sPSCs.  
    3. At P7 sPSCs were depolarizing, occasionally triggering a single action potential. By P18 the GABA reversal potential was shifted close to the resting potential and GGABA produced a shunting inhibition. Removal of GGABA by bicuculline increased granule cell excitability in response to current injection.  
    4. This novel tonic inhibition is present despite the low number of Golgi cell synapses on individual granule cells and appears to result from 'overspill' of synaptically released GABA leading to activation of synaptic and extrasynaptic GABAA receptors. "   See: 
Neuromodulators vs Neurotransmitters  
    5.  Does "synaptic inhibition in rat cerebellar granule cells" cause excitation or inhibition of the overall cerebellar output?   
    Free PMC Article   


1998    123<170 
Segregation of different GABAA receptors to synaptic and extrasynaptic membranes of cerebellar granule cells.
https://www.ncbi.nlm.nih.gov/pubmed/9464994
    "Two types of GABAA receptor-mediated inhibition (phasic and tonic) have been described in cerebellar granule cells, although these cells receive GABAergic input only from a single cell type, the Golgi cell.  
    In adult rats, granule cells express six GABAA receptor subunits abundantly (alpha1, alpha6, beta2, beta3, gamma2, and delta), which are coassembled into at least four to six distinct GABAA receptor subtypes. We tested whether a differential distribution of GABAA receptors on the surface of granule cells could play a role in the different forms of inhibition, assuming that phasic inhibition originates from the activation of synaptic receptors, whereas tonic inhibition is provided mainly by extrasynaptic receptors.  
    The alpha1, alpha6, beta2/3, and gamma2 subunits have been found by immunogold localizations to be concentrated in GABAergic Golgi synapses and also are present in the extrasynaptic membrane at a lower concentration. In contrast, immunoparticles for the delta subunit could not be detected in synaptic junctions, although they were abundantly present in the extrasynaptic dendritic and somatic membranes. Gold particles for the alpha6, gamma2, and beta2/3, but not the alpha1 and delta, subunits also were concentrated in some glutamatergic mossy fiber synapses, where their colocalization with AMPA-type glutamate receptors was demonstrated.  
    The exclusive extrasynaptic presence of the delta subunit-containing receptors, together with their kinetic properties, suggests that tonic inhibition could be mediated mainly by extrasynaptic alpha6beta2/3delta receptors, whereas phasic inhibition is attributable to the activation of synaptic alpha1beta2/3gamma2, alpha6beta2/3gamma2, and alpha1alpha6beta2/3gamma2 receptors. 
    My comments
1.  ... assuming that phasic inhibition originates from the activation of synaptic receptors, whereas tonic inhibition is provided mainly by extrasynaptic receptors.  
2.  ... glutamatergic mossy fiber synapses ... AMPA-type glutamate receptors   
3.  ... tonic inhibition could be mediated mainly by extrasynaptic alpha6beta2/3delta receptors, whereas phasic inhibition is attributable to the activation of synaptic alpha1beta2/3gamma2, alpha6beta2/3gamma2, and alpha1alpha6beta2/3gamma2 receptors.  
    Free Article   



2000   
117<170 
GABA spillover from single inhibitory axons suppresses low-frequency excitatory transmission at the cerebellar glomerulus.   
Free Article   


2001   
112<170   
Regulation of the expression of low affinity GABAA receptors in rat cerebellar granule cells.    


2002   
111<170      Free Article   
Pre- and postsynaptic inhibition mediated by GABA(B) receptors in cerebellar inhibitory interneurons.    


2002   
110<170    Free Article   
Tonic and spillover inhibition of granule cells control information flow through cerebellar cortex.  


2002   
106<170     Free Article 
Cerebellar cortex: computation by extrasynaptic inhibition?  


2002   
104<170    Free Article 
Depression of inhibitory synaptic transmission between Purkinje cells and neurons of the cerebellar nuclei.  


2003   
101<170 
Multiple modes of GABAergic inhibition of rat cerebellar granule cells.   


2010   
47<170 
Long-lasting inhibition of cerebellar output.  


2011   
43<170 
Cerebellar brain inhibition is decreased in active and surround muscles at the onset of voluntary movement. 


2012   
31<170    Free Article 
Tonic inhibition enhances fidelity of sensory information transmission in the cerebellar cortex.  


2013   
23<170  
A reinforcing circuit action of extrasynaptic GABAA receptor modulators on cerebellar granule cell inhibition.  


2014   
9<170 
Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition.   


2016   
4<170 
Cerebellar brain inhibition in the target and surround muscles during voluntary tonic activation.





SubC Cerebellar Tonic Inhibition\
161022 - 1318  

Comments