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Progress in Brain Research 2022This chapter summarizes early electrophysiological and lesion studies to elucidate cortical, subcortical and cerebellar mechanisms for extracting visual target motion...
This chapter summarizes early electrophysiological and lesion studies to elucidate cortical, subcortical and cerebellar mechanisms for extracting visual target motion and programming a smooth-pursuit response. The importance of a descending pursuit pathway from the middle temporal (MT) cortical visual area, which extracts the speed and direction of a moving target, the projections to dorsolateral pontine nuclei, and onto the cerebellum are outlined. Contributions of the cerebellum to pursuit are discussed and models are presented to account for the ways in which floccular gaze Purkinje cells behave during smooth pursuit, combined eye-head tracking, and during head rotation while viewing a stationary target.
Topics: Cerebellum; Humans; Neurophysiology; Purkinje Cells; Pursuit, Smooth; Reflex, Vestibulo-Ocular
PubMed: 35074066
DOI: 10.1016/bs.pbr.2021.10.021 -
Nature Reviews. Neurology Nov 2023Parkinson disease (PD) is characterized by heterogeneous motor and non-motor symptoms, resulting from neurodegeneration involving various parts of the central nervous... (Review)
Review
Parkinson disease (PD) is characterized by heterogeneous motor and non-motor symptoms, resulting from neurodegeneration involving various parts of the central nervous system. Although PD pathology predominantly involves the nigral-striatal system, growing evidence suggests that pathological changes extend beyond the basal ganglia into other parts of the brain, including the cerebellum. In addition to a primary involvement in motor control, the cerebellum is now known to also have an important role in cognitive, sleep and affective processes. Over the past decade, an accumulating body of research has provided clinical, pathological, neurophysiological, structural and functional neuroimaging findings that clearly establish a link between the cerebellum and PD. This Review presents an overview and update on the involvement of the cerebellum in the clinical features and pathogenesis of PD, which could provide a novel framework for a better understanding the heterogeneity of the disease.
Topics: Humans; Parkinson Disease; Cerebellum; Basal Ganglia; Brain; Corpus Striatum
PubMed: 37752351
DOI: 10.1038/s41582-023-00874-3 -
International Journal of Molecular... Feb 2024Although more than 30 different types of neuropeptides have been identified in various cell types and circuits of the cerebellum, their unique functions in the... (Review)
Review
Although more than 30 different types of neuropeptides have been identified in various cell types and circuits of the cerebellum, their unique functions in the cerebellum remain poorly understood. Given the nature of their diffuse distribution, peptidergic systems are generally assumed to exert a modulatory effect on the cerebellum via adaptively tuning neuronal excitability, synaptic transmission, and synaptic plasticity within cerebellar circuits. Moreover, cerebellar neuropeptides have also been revealed to be involved in the neurogenetic and developmental regulation of the developing cerebellum, including survival, migration, differentiation, and maturation of the Purkinje cells and granule cells in the cerebellar cortex. On the other hand, cerebellar neuropeptides hold a critical position in the pathophysiology and pathogenesis of many cerebellar-related motor and psychiatric disorders, such as cerebellar ataxias and autism. Over the past two decades, a growing body of evidence has indicated neuropeptides as potential therapeutic targets to ameliorate these diseases effectively. Therefore, this review focuses on eight cerebellar neuropeptides that have attracted more attention in recent years and have significant potential for clinical application associated with neurodegenerative and/or neuropsychiatric disorders, including brain-derived neurotrophic factor, corticotropin-releasing factor, angiotensin II, neuropeptide Y, orexin, thyrotropin-releasing hormone, oxytocin, and secretin, which may provide novel insights and a framework for our understanding of cerebellar-related disorders and have implications for novel treatments targeting neuropeptide systems.
Topics: Humans; Cerebellum; Purkinje Cells; Neurons; Cerebellar Cortex; Neuropeptides; Cerebellar Diseases
PubMed: 38397008
DOI: 10.3390/ijms25042332 -
Nature Neuroscience Jun 2023The cerebellum is hypothesized to refine movement through online adjustments. We examined how such predictive control may be generated using a mouse reach paradigm,...
The cerebellum is hypothesized to refine movement through online adjustments. We examined how such predictive control may be generated using a mouse reach paradigm, testing whether the cerebellum uses within-reach information as a predictor to adjust reach kinematics. We first identified a population-level response in Purkinje cells that scales inversely with reach velocity, pointing to the cerebellar cortex as a potential site linking kinematic predictors and anticipatory control. Next, we showed that mice can learn to compensate for a predictable reach perturbation caused by repeated, closed-loop optogenetic stimulation of pontocerebellar mossy fiber inputs. Both neural and behavioral readouts showed adaptation to position-locked mossy fiber perturbations and exhibited aftereffects when stimulation was removed. Surprisingly, position-randomized stimulation schedules drove partial adaptation but no opposing aftereffects. A model that recapitulated these findings suggests that the cerebellum may decipher cause-and-effect relationships through time-dependent generalization mechanisms.
Topics: Cerebellum; Purkinje Cells; Movement; Learning; Conditioning, Classical
PubMed: 37248339
DOI: 10.1038/s41593-023-01347-y -
Cerebellum (London, England) Aug 2022The first attempts at using electric stimulation to study human brain functions followed the experiments of Luigi Galvani and Giovanni Aldini on animal electricity... (Review)
Review
The first attempts at using electric stimulation to study human brain functions followed the experiments of Luigi Galvani and Giovanni Aldini on animal electricity during the eighteenth century. Since then, the cerebellum has been among the areas that have been studied by invasive and non-invasive forms of electrical and magnetic stimulation. During the nineteenth century, animal experiments were conducted to map the motor-related regions of cerebellar cortex by means of direct electric stimulation. As electric stimulation research on the cerebellum moved into the twentieth century, systematic research of electric cerebellar stimulation led to a better understanding of its effects and mechanism of action. In addition, the clinical potential of cerebellar stimulation in the treatment of motor diseases started to be explored. With the introduction of transcranial electric and magnetic stimulation, cerebellar research moved to non-invasive techniques. During the twenty-first century, following on groundbreaking research that linked the cerebellum to non-motor functions, non-invasive techniques have facilitated research into different aspects of cerebellar functioning. The present review provides a brief historical account of cerebellar neurostimulation and discusses current challenges and future direction in this field of research.
Topics: Animals; Cerebellar Cortex; Cerebellum; Electric Stimulation; Humans; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation
PubMed: 34403075
DOI: 10.1007/s12311-021-01310-2 -
Cerebellum (London, England) Oct 2022Electromagnetic brain stimulation is a promising treatment in neurology and psychiatry. However, clinical outcomes are variable and underlying mechanisms remain... (Review)
Review
Electromagnetic brain stimulation is a promising treatment in neurology and psychiatry. However, clinical outcomes are variable and underlying mechanisms remain ill-defined, impeding the development of new effective stimulation protocols. There is increasing application of repetitive transcranial magnetic stimulation (rTMS) to the cerebellum to induce forebrain plasticity through its long-distance cerebello-cerebral circuits. To better understand what magnetic stimulation does within the cerebellum, we have developed tools to generate defined low-intensity (LI) magnetic fields and deliver them in vivo, in 3D organotypic culture and in primary cultures, over a range of stimulation parameters. Here we show that low-intensity rTMS (LI-rTMS) to the cerebellum induces axon growth and synapse formation providing olivocerebellar reinnervation. This repair depends on stimulation pattern, with complex biomimetic patterns being most effective, and this requires the presence of a cellular magnetoreceptor, cryptochrome. To explain these reparative changes, we found that repair-promoting LI-rTMS patterns, but not ineffective ones, increased c-fos expression in Purkinje neurons, consistent with the production of reactive oxygen species by activated cryptochrome. Rather than activating neurons via induced electric currents, we propose that weak magnetic fields act through cryptochrome, activating intracellular signals that induce climbing fibre-Purkinje cell reinnervation. This information opens new routes to optimize cerebellar magnetic stimulation and its potential role as an effective treatment for neurological diseases.
Topics: Axons; Cerebellum; Cryptochromes; Purkinje Cells; Transcranial Magnetic Stimulation
PubMed: 35023064
DOI: 10.1007/s12311-021-01354-4 -
Dysphagia Apr 2023Swallowing is a complex activity requiring a sophisticated system of neurological control from neurones within the brainstem, cerebral cortices and cerebellum. The... (Review)
Review
Swallowing is a complex activity requiring a sophisticated system of neurological control from neurones within the brainstem, cerebral cortices and cerebellum. The cerebellum is a critical part of the brain responsible for the modulation of movements. It receives input from motor cortical and sensory areas and fine tunes these inputs to produce coordinated motor outputs. With respect to swallowing, numerous functional imaging studies have demonstrated increased activity in the cerebellum during the task of swallowing and damage to the cerebellum following differing pathological processes is associated with dysphagia. Single pulses of transcranial magnetic stimulation (TMS) have been applied to the cerebellum and have been shown to evoke motor responses in the pharynx. Moreover, repetitive TMS (rTMS) over the cerebellum can modulate cerebral motor (pharyngeal) cortical activity. Neurostimulation has allowed a better understanding of the connections that exist between the cerebellum and cerebral swallowing motor areas in health and provides a potential treatment for neurogenic dysphagia in illness. In this review we will examine what is currently known about the role of the cerebellum in the control of swallowing, explore new findings from neurostimulatory and imaging studies and provide an overview of the future clinical applications of cerebellar stimulation for treating dysphagia.
Topics: Humans; Deglutition; Deglutition Disorders; Evoked Potentials, Motor; Transcranial Magnetic Stimulation; Cerebellum
PubMed: 33675425
DOI: 10.1007/s00455-021-10271-x -
Cell Reports Apr 2024Pain that persists beyond the time required for tissue healing and pain that arises in the absence of tissue injury, collectively referred to as nociplastic pain, are...
Pain that persists beyond the time required for tissue healing and pain that arises in the absence of tissue injury, collectively referred to as nociplastic pain, are poorly understood phenomena mediated by plasticity within the central nervous system. The parabrachial nucleus (PBN) is a hub that relays aversive sensory information and appears to play a role in nociplasticity. Here, by preventing PBN Calca neurons from releasing neurotransmitters, we demonstrate that activation of Calca neurons is necessary for the manifestation and maintenance of chronic pain. Additionally, by directly stimulating Calca neurons, we demonstrate that Calca neuron activity is sufficient to drive nociplasticity. Aversive stimuli of multiple sensory modalities, such as exposure to nitroglycerin, cisplatin, or lithium chloride, can drive nociplasticity in a Calca-neuron-dependent manner. Aversive events drive nociplasticity in Calca neurons in the form of increased activity and excitability; however, neuroplasticity also appears to occur in downstream circuitry.
Topics: Animals; Parabrachial Nucleus; Neurons; Mice; Neuronal Plasticity; Male; Mice, Inbred C57BL
PubMed: 38583149
DOI: 10.1016/j.celrep.2024.114057 -
Journal of Neurophysiology Dec 2022A hedge fund billionaire's children are suffering from cerebellar disease. He invited a group of neuroscientists to plan a search for therapies. What resulted is the... (Review)
Review
A hedge fund billionaire's children are suffering from cerebellar disease. He invited a group of neuroscientists to plan a search for therapies. What resulted is the outline of an implantable neural emulator that might electronically replace the damaged part of the brain.
Topics: Male; Child; Humans; Purkinje Cells; Cerebellum; Cerebellar Diseases
PubMed: 36350062
DOI: 10.1152/jn.00437.2022 -
Journal of Integrative Neuroscience Jan 2022Apoptosis, autophagy and necrosis are the three main types of programmed cell death. One or more of these types of programmed cell death may take place in neurons... (Review)
Review
Apoptosis, autophagy and necrosis are the three main types of programmed cell death. One or more of these types of programmed cell death may take place in neurons leading to their death in various neurodegenerative disorders in humans. Purkinje neurons (PNs) are among the most highly vulnerable population of neurons to cell death in response to intrinsic hereditary diseases or extrinsic toxic, hypoxic, ischemic, and traumatic injury. In this review, we will describe the three main types of programmed cell death, including the molecular mechanisms and the sequence of events in each of them, and thus illustrating the intracellular proteins that mediate and regulate each of these types. Then, we will discuss the role of Ca2+ in PN function and increased vulnerability to cell death. Additionally, PN death will be described in animal models, namely lurcher mutant mouse and shaker mutant rat, in order to illustrate the potential therapeutic implications of programmed cell death in PNs by reviewing the previous studies that were carried out to interfere with the programmed cell death in an attempt to rescue PNs from death.
Topics: Animals; Apoptosis; Autophagy; Cerebellum; Humans; Mice; Necrosis; Neurodegenerative Diseases; Purkinje Cells; Rats
PubMed: 35164466
DOI: 10.31083/j.jin2101030