Papers by Nadia Cerminara
Journal of Neuroscience, 2010
Editor's Note: These short, critical reviews of recent papers in the Journal, written exclusively... more Editor's Note: These short, critical reviews of recent papers in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to summarize the important findings of the paper and provide additional insight and commentary. For more information on the format and purpose of the Journal Club, please see http://www.jneurosci.org/misc/ifa_features.shtml.
The cerebellum is the largest sensorimotor structure in the brain, but its mode of operation is n... more The cerebellum is the largest sensorimotor structure in the brain, but its mode of operation is not well understood. However, a fundamental organizational feature of the cerebellar cortex is division into elongated zones, defined by their inputs from specific parts of the inferior olive and Purkinje cell output to cerebellar and vestibular nuclei. Little is known about how the pattern of neuronal activity in zones, and their functional microcircuit subdivisions, microzones, is related to behaviour in awake animals. Here, we studied the organization of microzones within the C3 zone and their activity during a skilled forelimb reaching task in cats. Neurons in different parts of the C3 zone, functionally determined by receptive field characteristics, differed in their patterns of activity during movement. Our results suggest that the cerebellar C3 zone is organized and operates within an action-based frame of reference, with different microcircuits within the zone controlling specific...
Frontiers in Systems Neuroscience
Essential Tremor (ET) is a common movement disorder, characterised by a posture or movement-relat... more Essential Tremor (ET) is a common movement disorder, characterised by a posture or movement-related tremor of the upper limbs. Abnormalities within cerebellar circuits are thought to underlie the pathogenesis of ET, resulting in aberrant synchronous oscillatory activity within the thalamo-cortical network leading to tremors. Harmaline produces pathological oscillations within the cerebellum, and a tremor that phenotypically resembles ET. However, the neural network dynamics in cerebellar-thalamo-cortical circuits in harmaline-induced tremor remains unclear, including the way circuit interactions may be influenced by behavioural state. Here, we examined the effect of harmaline on cerebello-thalamo-cortical oscillations during rest and movement. EEG recordings from the sensorimotor cortex and local field potentials (LFP) from thalamic and medial cerebellar nuclei were simultaneously recorded in awake behaving rats, alongside measures of tremor using EMG and accelerometery. Analyses co...
Frontiers in Systems Neuroscience, 2021
The Cerebellum: From Embryology to Diagnostic Investigations, 2018
In this chapter, we compare current understanding of the anatomy and functional compartmentation ... more In this chapter, we compare current understanding of the anatomy and functional compartmentation of the human cerebellum with detailed knowledge in nonhuman species. The anatomy of the cerebellum is highly conserved across mammals and comparison of functional data suggests that similar principles of organization also hold true for somatotopy. In particular, there is a dual representation of the limbs in the cerebellar cortex in rat, ferret, cat, monkey, and human. In animals, a key organizing principle of the cerebellum is its division into a series of longitudinally oriented olivocorticonuclear modules that are narrow in the mediolateral axis but extend across multiple cerebellar lobules in the rostrocaudal plane. This contrasts with existing understanding of the human cerebellum that suggests that functional compartmentation is organized mainly at the level of different lobes and lobules. However, advances in spatial resolution of imaging techniques mean we are now able to start to examine whether a longitudinal modular organization is also present within the human cerebellum. This has implications for the diagnosis and future treatment of clinical disorders that involve the cerebellum, since it is possible that variations in symptomatology may relate to this finer grain localization.
Purkinje cells are the principal neurons of the cerebellar cortex. One of their distinguishing fe... more Purkinje cells are the principal neurons of the cerebellar cortex. One of their distinguishing features is that they fire two distinct types of action potential, called simple and complex spikes, which interact with one another. Simple spikes are stereotypical action potentials that are elicited at high, but variable, rates (0 – 100 Hz) and have a consistent waveform. Complex spikes are composed of an initial action potential followed by a burst of lower amplitude spikelets. Complex spikes occur at comparatively low rates (~ 1 Hz) and have a variable waveform. Although they are critical to cerebellar operation a simple model that describes the complex spike waveform is lacking. Here, a novel single-compartment model of Purkinje cell electrodynamics is presented. The simpler version of this model, with two active conductances and a leak channel, can simulate the features typical of complex spikes recorded in vitro. If calcium dynamics are also included, the model can capture the paus...
Damage to the cerebellum during posterior fossa surgery can lead to ataxia and in paediatric case... more Damage to the cerebellum during posterior fossa surgery can lead to ataxia and in paediatric cases, the risk of cerebellar mutism syndrome. Animal electrophysiological and human imaging studies have shown compartmentalisation of sensorimotor and cognitive functions within the cerebellum. In the present study, electrophysiological monitoring of sensory and motor pathways was carried out to assess the location of limb sensorimotor representation within the human cerebellum, as a potential approach for real time assessment of neurophysiological integrity to reduce the incidence of cerebellar surgical morbidities.Thirteen adult and paediatric patients undergoing posterior fossa surgery were recruited. For sensory mapping (n=8), electrical stimulation was applied to the median nerves, the posterior tibial nerves, or proximal and distal limb muscles and evoked field potential responses were sought on the cerebellar surface. For motor mapping (n=5), electrical stimulation was applied to th...
Physiology News, 2010
These guidelines are intended to assist authors in writing their contributions and to reduce the ... more These guidelines are intended to assist authors in writing their contributions and to reduce the subsequent editing process. The Editorial Board of Physiology News tries to ensure that all articles are written in a journalistic style so that they will have an immediate interest value for a wide readership and will be readable and comprehensible to non-experts. Scientific articles should give a good overview of a field rather than focus entirely on the authors' own research.
Beta frequency oscillations in scalp electroencephalography (EEG) recordings over the primary mot... more Beta frequency oscillations in scalp electroencephalography (EEG) recordings over the primary motor cortex have been associated with the preparation and execution of voluntary movements. Here, we test whether changes in beta frequency are related to the preparation of adapted movements in human, and whether such effects generalise to other species (cat). Eleven healthy adult humans performed a joystick visuomotor adaptation task. Beta (15-25Hz) scalp EEG signals recorded over the motor cortex during a pre-movement preparatory phase were, on average, significantly reduced in amplitude during early adaptation trials compared to baseline or late adaptation trials (p=0.01). The changes in beta were not related to measurements of reaction time or duration of the reach. We also recorded LFP activity within the primary motor cortex of three cats during a prism visuomotor adaptation task. Analysis of these signals revealed similar reductions in motor cortical LFP beta frequencies during ear...
Neuron, 2019
Preparatory activity is found across the motor network. In this issue of Neuron, Chabrol et al., ... more Preparatory activity is found across the motor network. In this issue of Neuron, Chabrol et al., (2019) show that preparatory activity in the anterior lateral motor cortex (ALM) and cerebellum is related to the prediction of reward delivery and that the cerebellum provides a learned timing signal to the ALM.
Human Brain Mapping, 2019
The cerebellum is involved in a wide range of behaviours. A key organisational principle from ani... more The cerebellum is involved in a wide range of behaviours. A key organisational principle from animal studies is that somatotopically corresponding sensory input and motor output reside in the same cerebellar cortical areas. However, compelling evidence for a similar arrangement in humans and whether it extends to cognitive functions is lacking. To address this, we applied cerebellar optimised whole-brain functional MRI in 20 healthy subjects. To assess spatial overlap within the sensorimotor and cognitive domains, we recorded activity to a sensory stimulus (vibrotactile) and a motor task; the Sternberg verbal working memory (VWM) task; and a verb generation paradigm. Consistent with animal data, sensory and motor activity overlapped with a somatotopic arrangement in ipsilateral areas of the anterior and posterior cerebellum. During the maintenance phase of the Sternberg task, a positive linear relationship between VWM load and activity was observed in right Lobule VI, extending into Crus I bilaterally. Articulatory movement gave rise to bilateral activity in medial Lobule VI. A conjunction of two independent language tasks localised activity during verb generation in right Lobule VI-Crus I, which overlapped with activity during VWM. These results demonstrate spatial compartmentalisation of sensorimotor and cognitive function in the human cerebellum, with each area involved in more than one aspect of a given behaviour, consistent with an integrative function. Sensorimotor localisation was uniform across individuals, but the representation of cognitive tasks was more variable, highlighting the importance of individual scans for mapping higher order functions within the cerebellum.
The Journal of physiology, 2017
Cerebellar Purkinje cells (PCs) generate two types of action potentials, simple and complex spike... more Cerebellar Purkinje cells (PCs) generate two types of action potentials, simple and complex spikes. Although they are generated by distinct mechanisms, interactions between the two spike types exist. Zebrin staining produces alternating positive and negative stripes of PCs across most of the cerebellar cortex. Thus, here we compared simple spike-complex spike interactions both within and across zebrin populations. Simple spike activity undergoes a complex modulation preceding and following a complex spike. The amplitudes of the pre- and post-complex spike modulation phases were correlated across PCs. On average, the modulation was larger for PCs in zebrin positive regions. Correlations between aspects of the complex spike waveform and simple spike activity were found, some of which varied between zebrin positive and negative PCs. The implications of the results are discussed with regard to hypotheses that complex spikes are triggered by rises in simple spike activity for either moto...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 14, 2016
The dorsal and ventral periaqueductal gray (dPAG and vPAG, respectively) are embedded in distinct... more The dorsal and ventral periaqueductal gray (dPAG and vPAG, respectively) are embedded in distinct survival networks that coordinate, respectively, innate and conditioned fear-evoked freezing. However, the information encoded by the PAG during these survival behaviors is poorly understood. Recordings in the dPAG and vPAG in rats revealed differences in neuronal activity associated with the two behaviors. During innate fear, neuronal responses were significantly greater in the dPAG compared with the vPAG. After associative fear conditioning and during early extinction (EE), when freezing was maximal, a field potential was evoked in the PAG by the auditory fear conditioned stimulus (CS). With repeated presentations of the unreinforced CS, animals displayed progressively less freezing accompanied by a reduction in event-related field potential amplitude. During EE, the majority of dPAG and vPAG units increased their firing frequency, but spike-triggered averaging showed that only ventra...
Annals of neurology, Jan 23, 2016
Friedreich's ataxia is a devastating neurological disease currently lacking any proven treatm... more Friedreich's ataxia is a devastating neurological disease currently lacking any proven treatment. We studied the neuro-protective effects of the cytokines granulocyte-colony stimulating factor and stem cell factor in a humanised murine model of Friedreich's ataxia. Mice received monthly subcutaneous infusions of cytokines while also being assessed at monthly time points using an extensive range of behavioural motor performance tests. After 6 months of treatment, neurophysiological evaluation of both sensory and motor nerve conduction was performed. Subsequently, mice were sacrificed for mRNA, protein and histological analysis of the dorsal root ganglion, spinal cord and cerebellum. Cytokine administration resulted in significant reversal of biochemical, neuropathological, neurophysiological and behavioural deficits associated with Friedreich's ataxia. Both granulocyte-colony stimulating factor and stem cell factor had pronounced effects on frataxin levels (the primary mo...
The Journal of physiology, Jan 6, 2016
Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action... more Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes. Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets. The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear. We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number. This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes...
Cerebellum (London, England), Feb 19, 2016
For many decades, the predominant view in the cerebellar field has been that the olivocerebellar ... more For many decades, the predominant view in the cerebellar field has been that the olivocerebellar system's primary function is to induce plasticity in the cerebellar cortex, specifically, at the parallel fiber-Purkinje cell synapse. However, it has also long been proposed that the olivocerebellar system participates directly in motor control by helping to shape ongoing motor commands being issued by the cerebellum. Evidence consistent with both hypotheses exists; however, they are often investigated as mutually exclusive alternatives. In contrast, here, we take the perspective that the olivocerebellar system can contribute to both the motor learning and motor control functions of the cerebellum and might also play a role in development. We then consider the potential problems and benefits of it having multiple functions. Moreover, we discuss how its distinctive characteristics (e.g., low firing rates, synchronization, and variable complex spike waveforms) make it more or less sui...
Progress in Brain Research, 2005
The lateral cerebellum receives an abundance of visual input providing the link between visual an... more The lateral cerebellum receives an abundance of visual input providing the link between visual and motor control centers. In this review we discuss experiments designed to increase our understanding of how visual inputs to the cerebellum are arranged in relation to the zonal organization of the cerebellar cortex, and how visual inputs are utilized to assist in the regulation of a visually guided movement. On the basis of anatomical and physiological characteristics our findings indicate that the medial-most folium in crus I of the cat lateral cerebellum can be subdivided into at least three functionally distinct zones; from lateral to medial along the length of the folium these correspond to zones D(1), lateral C(3) and C(2). Each zone displays clear differences in olivo-cortico-nuclear connectivity and in the anesthetized animal zones D(1) and C(2) both receive powerful visual inputs relayed via the climbing fiber system. Complementary experiments in awake behaving cats found that Purkinje cells located in the D(1) and D(2) zones of crus I exhibit changes in simple spike discharge time locked to target motion during a visually guided reaching task. These changes were unaffected by temporary visual denial of the target, raising the possibility that internally generated feedforward visuomotor control mechanisms are operating, in which a predictive model of the target's motion has been constructed by the CNS.
Frontiers in Neural Circuits, 2013
How does the cerebellum, the brain's largest sensorimotor structure, contribute to complex behavi... more How does the cerebellum, the brain's largest sensorimotor structure, contribute to complex behaviors essential to survival? While we know much about the role of limbic and closely associated brainstem structures in relation to a variety of emotional, sensory, or motivational stimuli, we know very little about how these circuits interact with the cerebellum to generate appropriate patterns of behavioral response. Here we focus on evidence suggesting that the olivo-cerebellar system may link to survival networks via interactions with the midbrain periaqueductal gray, a structure with a well known role in expression of survival responses. As a result of this interaction we argue that, in addition to important roles in motor control, the inferior olive, and related olivo-cortico-nuclear circuits, should be considered part of a larger network of brain structures involved in coordinating survival behavior through the selective relaying of "teaching signals" arising from higher centers associated with emotional behaviors.
Nature Reviews Neuroscience, 2015
The adult mammalian cerebellar cortex is generally assumed to have a uniform cytoarchitecture. Di... more The adult mammalian cerebellar cortex is generally assumed to have a uniform cytoarchitecture. Differences in cerebellar function are thought to arise, in the main, through distinct patterns of input and output connectivity, rather than as a result of variations in cortical microcircuitry. However, evidence from anatomical, physiological and genetic studies is increasingly challenging this orthodoxy and there are now various lines of evidence that the cerebellar cortex is non uniform. Here we develop the hypothesis that regional differences in cerebellar cortical microcircuit properties lead to important differences in information processing.
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Papers by Nadia Cerminara