Dysfunction of parvalbumin neurons in the cerebellar nuclei produces an action tremor

Abstract Purpose Diaschisis of cerebrocerebellar loops contributes to cognitive and motor deficits in pediatric cerebellar brain tumor survivors. We used a cerebellar white matter atlas and hypothesized that lesion symptom mapping may reveal the critical lesions of cerebellar tracts. Methods We examined 31 long-term survivors of pediatric posterior fossa tumors (13 pilocytic astrocytoma, 18 medulloblastoma). Patients underwent neuronal imaging, examination for ataxia, fine motor and cognitive function, planning abilities, and executive function. Individual consolidated cerebellar lesions were drawn manually onto patients’ individual MRI and normalized into Montreal Neurologic Institute (MNI) space for further analysis with voxel-based lesion symptom mapping. Results Lesion symptom mapping linked deficits of motor function to the superior cerebellar peduncle (SCP), deep cerebellar nuclei (interposed nucleus (IN), fastigial nucleus (FN), ventromedial dentate nucleus (DN)), and inferior vermis (VIIIa, VIIIb, IX, X). Statistical maps of deficits of intelligence and executive function mapped with minor variations to the same cerebellar structures. Conclusion We identified lesions to the SCP next to deep cerebellar nuclei as critical for limiting both motor and cognitive function in pediatric cerebellar tumor survivors. Future strategies safeguarding motor and cognitive function will have to identify patients preoperatively at risk for damage to these critical structures and adapt multimodal therapeutic options accordingly.

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Diurnal changes in perineuronal nets and parvalbumin neurons in the rat medial prefrontal cortex

Brain Structure and Function ◽

10.1007/s00429-021-02229-4 ◽

2021 ◽

Author(s):

John H. Harkness ◽

Angela E. Gonzalez ◽

Priyanka N. Bushana ◽

Emily T. Jorgensen ◽

Deborah M. Hegarty ◽

...

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Perineuronal Nets ◽

Diurnal Changes ◽

Parvalbumin Neurons

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A model of on/off transitions in neurons of the deep cerebellar nuclei: deciphering the underlying ionic mechanisms

The Journal of Mathematical Neuroscience ◽

10.1186/s13408-021-00105-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hugues Berry ◽

Stéphane Genet

Keyword(s):

Cerebellar Nuclei ◽

Biophysical Model ◽

High Threshold ◽

Deep Cerebellar Nuclei ◽

Functional Link ◽

Electrophysiological Properties ◽

Voltage Dependent ◽

Ionic Mechanisms ◽

The Central Nervous System ◽

Overall Functioning

AbstractThe neurons of the deep cerebellar nuclei (DCNn) represent the main functional link between the cerebellar cortex and the rest of the central nervous system. Therefore, understanding the electrophysiological properties of DCNn is of fundamental importance to understand the overall functioning of the cerebellum. Experimental data suggest that DCNn can reversibly switch between two states: the firing of spikes (F state) and a stable depolarized state (SD state). We introduce a new biophysical model of the DCNn membrane electro-responsiveness to investigate how the interplay between the documented conductances identified in DCNn give rise to these states. In the model, the F state emerges as an isola of limit cycles, i.e. a closed loop of periodic solutions disconnected from the branch of SD fixed points. This bifurcation structure endows the model with the ability to reproduce the $\text{F}\to \text{SD}$ F → SD transition triggered by hyperpolarizing current pulses. The model also reproduces the $\text{F}\to \text{SD}$ F → SD transition induced by blocking Ca currents and ascribes this transition to the blocking of the high-threshold Ca current. The model suggests that intracellular current injections can trigger fully reversible $\text{F}\leftrightarrow \text{SD}$ F ↔ SD transitions. Investigation of low-dimension reduced models suggests that the voltage-dependent Na current is prominent for these dynamical features. Finally, simulations of the model suggest that physiological synaptic inputs may trigger $\text{F}\leftrightarrow \text{SD}$ F ↔ SD transitions. These transitions could explain the puzzling observation of positively correlated activities of connected Purkinje cells and DCNn despite the former inhibit the latter.

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Anatomy of Motor Learning. II. Subcortical Structures and Learning by Trial and Error

Journal of Neurophysiology ◽

10.1152/jn.1997.77.3.1325 ◽

1997 ◽

Vol 77 (3) ◽

pp. 1325-1337 ◽

Cited By ~ 294

Author(s):

M. Jueptner ◽

C. D. Frith ◽

D. J. Brooks ◽

R.S.J. Frackowiak ◽

R. E. Passingham

Keyword(s):

Motor Learning ◽

Response Times ◽

Cerebellar Nuclei ◽

Selection Task ◽

Systematic Change ◽

Trial And Error ◽

Subcortical Structures ◽

Learning Condition ◽

Positron Emission ◽

New Learning

Jueptner, M., C. D. Frith, D. J. Brooks, R.S.J. Frackowiak, and R. E. Passingham. Anatomy of motor learning. II. Subcortical structures and learning by trial and error. J. Neurophysiol. 77: 1325–1337, 1997. We used positron emission tomography to study motor learning by trial and error. Subjects learned sequences of eight finger movements. Tones generated by a computer told the subjects whether any particular move was correct or incorrect. A control condition was used in which the subjects generated moves, but there was no feeback to indicate success or failure, and so no learning occured. In this condition (free selection) the subjects were required to make a finger movement on each trial and to vary the movements randomly over trials. The subjects had a free choice of which finger to move on any one trial. On this task there was no systematic change in responses over trials and no change in the response times. Two other conditions were included. In one the subjects repetitively moved the same finger on all trials and in a baseline condition the subjects heard the pacing tones and auditory feedback but made no movements. Comparing new learning with the free selection task, there was a small activation in the right prefrontal cortex. This may reflect the fact that in new learning, but not free selection, the subjects rehearse past moves and adapt their responses accordingly. The caudate nucleus was strongly activated during new learning. It is suggested that this activity may be related either to mental rehearsal or to reinforcement of the movements as a consequence of the outcomes. The putamen was activated anteriorly on the free selection task and more posteriorly when the subjects repetitively made the same movement. It is suggested that the differences in the location of the peak activation in the striatum may represent the operation of different corticostriatal loops. The cerebellar nuclei (bilaterally) and vermis were more active in the new learning condition than during the performance of the free selection task. There was no difference in the activation of the cerebellum when the free selection task was compared with repetitive performance of the same movement. We tentatively suggest that the basal ganglia may be involved in the specification of movement on the basis of memory of either the movements or the outcomes, but that the cerebellum may be more directly involved in changes in the parameters of movement execution.

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Developmental Expression of Calcium-Binding Protein-Containing Neurons in Neocortical Transplants

Cell Transplantation ◽

10.1177/096368979800700207 ◽

1998 ◽

Vol 7 (2) ◽

pp. 121-129 ◽

Cited By ~ 2

Author(s):

Jeffrey M. Rosenstein ◽

Newton S. More ◽

Nina Mani ◽

Janette M. Krum

Keyword(s):

Oxidative Stress ◽

Cortical Neurons ◽

Calcium Binding ◽

Binding Protein ◽

Substantial Reduction ◽

Qualitative Change ◽

Afferent Input ◽

Calcium Binding Protein ◽

Developmental Expression ◽

Parvalbumin Neurons

The present study examined the development of calcium binding protein-containing neurons in a timed series of fetal neocortical transplants. The immunoexpression of parvalbumin and calbindin, which are subpopulations of GABAergic neurons, have been widely studied in normal development and in disease and injury states. Because of their purported resistance to oxidative injury by their ability to buffer Ca++ influx, these neurons have been particularly studied following ischemia. Because it is likely that oxidative stress is associated with the grafting procedure, we sought to determine if these neurons displayed enhanced survival characteristics. Normally, parvalbumin and calbindin represent about 5-10% of cortical neurons. Within 2-4 wk after grafting the expression of both proteins increased markedly in that a relatively larger number of neurons (27% for parvalbumin) were immunopositive. This increase was transitory, however, and by 4 mo and beyond, confocal microscopic data showed a reduction of over 50% of parvalbumin (+) neurons and processes. Calbindin (+) processes showed a qualitative change in that they were smaller with less terminal branching. Electron microscopy confirmed a substantial reduction in parvalbumin synaptic contacts. Interestingly, in older grafts, remaining parvalbumin neurons were those that were strongly NSE (+) suggesting a link between normal metabolism and Ca++ buffering in grafted neurons. It is possible that in early grafts certain neuronal populations transiently upregulated calcium binding proteins as a defensive mechanism against Ca++ influx associated with oxidative stress. Over time, however, following physiological normalization within grafts, the calcium binding protein (+) neurons are diminished, possibly due to lack of appropriate afferent input to the interneuronal pool.

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Role of the Vermal Cerebellum in Visually Guided Eye Movements and Visual Motion Perception

Annual Review of Vision Science ◽

10.1146/annurev-vision-091718-015000 ◽

2019 ◽

Vol 5 (1) ◽

pp. 247-268 ◽

Cited By ~ 1

Author(s):

Peter Thier ◽

Akshay Markanday

Keyword(s):

Eye Movements ◽

Motion Perception ◽

Visual Motion ◽

Cerebellar Nuclei ◽

Visually Guided ◽

Past Performance ◽

Visual Motion Perception ◽

Oculomotor Vermis ◽

Retinal Information

The cerebellar cortex is a crystal-like structure consisting of an almost endless repetition of a canonical microcircuit that applies the same computational principle to different inputs. The output of this transformation is broadcasted to extracerebellar structures by way of the deep cerebellar nuclei. Visually guided eye movements are accommodated by different parts of the cerebellum. This review primarily discusses the role of the oculomotor part of the vermal cerebellum [the oculomotor vermis (OMV)] in the control of visually guided saccades and smooth-pursuit eye movements. Both types of eye movements require the mapping of retinal information onto motor vectors, a transformation that is optimized by the OMV, considering information on past performance. Unlike the role of the OMV in the guidance of eye movements, the contribution of the adjoining vermal cortex to visual motion perception is nonmotor and involves a cerebellar influence on information processing in the cerebral cortex.

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