Richard Apps

Richard Apps
University of Bristol | UB · School of Physiology, Pharmacology and Neuroscience

Professor of Neuroscience

About

132
Publications
28,833
Reads
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5,436
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Introduction
The overall aim of my research is to understand the contributions the mammalian cerebellum makes to the control of goal directed movements and defence behaviours. My lab uses a combination of systems level anatomical, physiological and behavioural techniques to examine cerebellar structure-function relationships with a focus on the climbing fibre system which plays a vital but enigmatic role in cerebellar function.
Additional affiliations
August 2011 - October 2013
University of Bristol
Position
  • Director of Bristol Neuroscience

Publications

Publications (132)
Article
Full-text available
Unlabelled: The periaqueductal gray (PAG) coordinates behaviors essential to survival, including striking changes in movement and posture (e.g., escape behaviors in response to noxious stimuli vs freezing in response to fear-evoking stimuli). However, the neural circuits underlying the expression of these behaviors remain poorly understood. We dem...
Article
Full-text available
Unlabelled: Pathways arising from the periphery that target the inferior olive [spino-olivocerebellar pathways (SOCPs)] are a vital source of information to the cerebellum and are modulated (gated) during active movements. This limits their ability to forward signals to climbing fibers in the cerebellar cortex. We tested the hypothesis that the te...
Article
Full-text available
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...
Article
Full-text available
Objectives: 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. Methods: Mice received monthly subcutaneous infusions of cytokines wh...
Article
Full-text available
The loss of descending inhibitory control is thought critical to the development of chronic pain but what causes this loss in function is not well understood. We have investigated the dynamic contribution of prelimbic cortical neuronal projections to the periaqueductal grey (PrL-P) to the development of neuropathic pain in rats using combined opto-...
Article
Full-text available
Cerebellum is a key-structure for the modulation of motor, cognitive, social and affective functions, contributing to automatic behaviours through interactions with the cerebral cortex, basal ganglia and spinal cord. The predictive mechanisms used by the cerebellum cover not only sensorimotor functions but also reward-related tasks. Cerebellar circ...
Article
The role of neuromodulators in the cerebellum is not well understood. In particular, the behavioural significance of the cholinergic system in the cerebellum is unknown. To investigate the importance of cerebellar cholinergic signalling in behaviour, we infused acetylcholine receptor antagonists, scopolamine and mecamylamine, bilaterally into the r...
Chapter
The cerebellum is typically associated with motor control although there is now extensive evidence that its involvement extends into other domains including cognitive processing. The cerebellum contains a highly regular neural organization, but exactly how this circuitry contributes to its diverse functions remains unclear. Patterns of inputs to an...
Article
Full-text available
Introduction: The extinction of fear memories is an important component in regulating defensive behaviors, contributing toward adaptive processes essential for survival. The cerebellar medial nucleus (MCN) has bidirectional connections with the ventrolateral periaqueductal gray (vlPAG) and is implicated in the regulation of multiple aspects of fea...
Article
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The role of the cerebellum in emotional control has gained increasing interest, with studies showing it is involved in fear learning and memory in both humans and rodents. This review will focus on the contributions of the cerebellum to the extinction of learned fear responses. Extinction of fearful memories is critical for adaptive behaviour, and...
Article
Full-text available
Behavioural feedback is critical for learning in the cerebral cortex. However, such feedback is often not readily available. How the cerebral cortex learns efficiently despite the sparse nature of feedback remains unclear. Inspired by recent deep learning algorithms, we introduce a systems-level computational model of cerebro-cerebellar interaction...
Article
Full-text available
The cerebellum is the largest sensorimotor structure in the brain. A fundamental organizational feature of its cortex is its division into a series of rostrocaudally elongated zones. These are defined by their inputs from specific parts of the inferior olive and Purkinje cell output to specific cerebellar and vestibular nuclei. However, little is k...
Article
Full-text available
Given the importance of the cerebellum in controlling movements, it might be expected that its main role in eating would be the control of motor elements such as chewing and swallowing. Whilst such functions are clearly important, there is more to eating than these actions, and more to the cerebellum than motor control. This review will present evi...
Article
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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 path...
Article
Full-text available
The pivotal role of the periaqueductal grey (PAG) in fear learning is reinforced by the identification of neurons in male rat ventrolateral PAG (vlPAG) that encode fear memory through signalling the onset and offset of an auditory-conditioned stimulus during presentation of the unreinforced conditioned tone (CS+) during retrieval. Some units only d...
Preprint
Full-text available
Behavioural feedback is critical for learning in the cerebral cortex. However, such feedback is often not readily available. How the cerebral cortex learns efficiently despite the sparse nature of feedback remains unclear. Inspired by recent deep learning algorithms, we introduce a systems-level computational model of cerebro-cerebellar interaction...
Article
Full-text available
Cerebellar damage during posterior fossa surgery in children can lead to ataxia and risk of cerebellar mutism syndrome. Compartmentalisation of sensorimotor and cognitive functions within the cerebellum have been demonstrated in animal electrophysiology and human imaging studies. Electrophysiological monitoring was carried out under general anaesth...
Chapter
A key organizational feature of the cerebellum is its division into a series of cerebellar modules. The cortical component of each module is termed a zone. Each zone is defined by its climbing input originating from a well-defined region of the inferior olive, which targets one or more longitudinal zones of Purkinje cells within the cerebellar cort...
Preprint
The brain solves the credit assignment problem remarkably well. For credit to be assigned across neural networks they must, in principle, wait for specific neural computations to finish. How the brain deals with this inherent locking problem has remained unclear. Deep learning methods suffer from similar locking constraints both on the forward and...
Preprint
Full-text available
Cerebellar damage during posterior fossa surgery in children can lead to ataxia and risk of cerebellar mutism syndrome. Compartmentalisation of sensorimotor and cognitive functions within the cerebellum have been demonstrated in animal electrophysiology and human imaging studies. Electrophysiological monitoring was carried out to assess the limb se...
Preprint
Full-text available
The pivotal role of the periaqueductal grey (PAG) in fear learning is reinforced by the identification of neurons in rat ventral (vPAG) that encode fear memory through signalling the onset and offset of an auditory conditioned stimulus during retrieval. Within this framework, understanding of cerebellar contributions to survival circuits is advance...
Preprint
Full-text available
The loss of descending inhibitory control is thought critical to the development of chronic pain but what causes this loss in function is not well understood. We have investigated the dynamic contribution of prelimbic cortical neuronal projections to the periaqueductal grey (PrL-P) to the development of neuropathic pain in rats using combined opto-...
Article
Full-text available
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...
Poster
The cerebellum is recognised as a major structure for coordinating skilled movements and facilitating motor adaptation. Motor adaptation is an essential form of sensorimotor learning, whereby our motor actions are continually updated to adapt to sensory perturbations, enabling us to maintain accurate goal directed movements. Studies in patients wit...
Preprint
Full-text available
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...
Preprint
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 sens...
Preprint
Full-text available
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....
Preprint
Full-text available
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...
Article
Full-text available
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...
Chapter
The cerebro-cerebellar system is one of the largest pathways in the central nervous system, yet knowledge of its structure and function remains far from complete. This is an important gap in understanding because anatomical connectivity is a key determinant of cerebellar function. This updated chapter focuses on recent advances in understanding the...
Article
Full-text available
Time perception is an essential element of conscious and subconscious experience, coordinating our perception and interaction with the surrounding environment. In recent years, major technological advances in the field of neuroscience have helped foster new insights into the processing of temporal information, including extending our knowledge of t...
Article
Full-text available
How the cerebellum carries out its functions is not clear, even for its established roles in motor control. In particular, little is known about how the cerebellar nuclei (CN) integrate their synaptic and neuromodulatory inputs to generate cerebellar output. CN neurons receive inhibitory inputs from Purkinje cells, excitatory inputs from mossy fibr...
Article
Full-text available
The compartmentalization of the cerebellum into modules is often used to discuss its function. What, exactly, can be considered a module, how do they operate, can they be subdivided and do they act individually or in concert are only some of the key questions discussed in this consensus paper. Experts studying cerebellar compartmentalization give t...
Article
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In the original version of this paper, the Title should have been written with "A Consensus paper" to read "Cerebellar Modules and Their Role as Operational Cerebellar Processing Units: A Consensus paper".
Article
Full-text available
The cerebellum has a striking homogeneous cytoarchitecture and participates in both motor and non-motor domains. Indeed, a wealth of evidence from neuroanatomical, electrophysiological, neuroimaging and clinical studies has substantially modified our traditional view on the cerebellum as a sole calibrator of sensorimotor functions. Despite the majo...
Chapter
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 pa...
Article
Full-text available
Objectives Various regions of the midbrain and cerebrum are known to play an important role in fear behaviour. This talk will present evidence that the cerebellum should also be added to this network. Methods Electrophysiological, lesioning and behavioural techniques in rats were used to study interactions between the cerebellum and the midbrain p...
Article
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The principal source of synaptic inputs to the cerebellum arise from mossy fibres and climbing fibres (CFs). This article is protected by copyright. All rights reserved
Article
Full-text available
Key points: 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 si...
Article
Recent studies of trans-cranial Direct Current stimulation (tDCS) have raised the possibility that this is a relatively simple and well tolerated method that can be used as an effective therapeutic tool to treat neurological and neuropsychiatric disorders (Grimaldir et al., 2016). In particular, stimulation of the cerebellum (ctDCS) in humans has b...
Article
Full-text available
The ability to interact with challenging environments requires coordination of sensory and motor systems that underpin appropriate survival behaviours. All animals, including humans, use active and passive coping strategies to react to escapable or inescapable threats respectively. Across species the neural pathways involved in survival behaviours...
Article
Full-text available
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 help...
Article
Full-text available
Key points 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 a...
Chapter
Full-text available
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 helpi...
Book
Full-text available
Accumulating evidence suggests that the cerebellum subserves functions beyond the sensorimotor realm. This possibility has received considerable attention during the past quarter century, with recent findings revealing putative cerebellar roles in cognition, emotion and spatial navigation. These functions are potentially underpinned by the behaviou...
Book
Full-text available
Accumulating evidence suggests that the cerebellum subserves functions beyond the sensorimotor realm. This possibility has received considerable attention during the past quarter century, with recent findings revealing putative cerebellar roles in cognition, emotion and spatial navigation. These functions are potentially underpinned by the behaviou...
Article
Full-text available
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 geneti...
Article
Full-text available
The adult mammalian cerebellar cortex is generally assumed to have a uniform cytoarchitecture. Differences in cerebellar function are thought to arise primarily 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 stu...
Article
Full-text available
The proceedings of the workshop synthesize the experimental, preclinical, and clinical data suggesting that the cerebellum, basal ganglia (BG), and their connections play an important role in pathophysiology of various movement disorders (like Parkinson's disease and atypical parkinsonian syndromes) or neurodevelopmental disorders (like autism). Th...
Article
Full-text available
The UVB and heat rekindling (UVB/HR) model shows potential as a translatable inflammatory pain model. However, the occurrence of central sensitization in this model, a fundamental mechanism underlying chronic pain, has been debated. Face, construct and predictive validity are key requisites of animal models; electromyogram (EMG) recordings were uti...
Article
Full-text available
In contrast to the uniform anatomy of the cerebellar cortex, molecular and physiological studies indicate that significant differences exist between cortical regions, suggesting that the spiking activity of Purkinje cells (PCs) in different regions could also show distinct characteristics. To investigate this possibility we obtained extracellular r...
Article
Full-text available
The gracile nucleus (GN) and dorsal accessory olive (DAO) are important relays for indirect (post synaptic dorsal column) and direct ascending pathways respectively that terminate as climbing fibres in the 'hindlimb-receiving' parts of the C1 and C3 zones in the cerebellar cortex. While the spinal cells of origin of GN and DAO are from largely sepa...
Data
Lesion of the cerbellar pyramis reduces freezing behaviour in response to associatively conditioned fear.
Data
Lesion of the cerebellar pyramis reduces innate freezing behaviour in response to cat odour.
Article
Full-text available
Key points At the heart of the brain circuitry underlying fear behaviour is the periaqueductal grey (PAG). We address an important gap in understanding regarding the neural pathways and mechanisms that link the PAG to distinct patterns of motor response associated with survival behaviours. We identify a highly localised part of the cerebellum (late...
Article
Full-text available
Although recent neuroanatomical evidence has demonstrated closed-loop connectivity between prefrontal cortex and the cerebellum, the physiology of cerebello-cerebral circuits and the extent to which cerebellar output modulates neuronal activity in neocortex during behavior remain relatively unexplored. We show that electrical stimulation of the con...
Article
Full-text available
The topography of the cerebellar cortex is described by at least three different maps, with the basic units of each map termed "microzones," "patches," and "bands." These are defined, respectively, by different patterns of climbing fiber input, mossy fiber input, and Purkinje cell (PC) phenotype. Based on embryological development, the "one-map" hy...
Article
Full-text available
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 ce...
Article
Full-text available
In the present paper, we examine the role of the cerebellar interpositus nucleus (IN) in motor and non-motor domains. Recent findings are considered, and we share the following conclusions: IN as part of the olivo-cortico-nuclear microcircuit is involved in providing powerful timing signals important in coordinating limb movements; IN could partici...
Chapter
Full-text available
The cerebro-cerebellar system is one of the largest pathways in the central nervous system, yet knowledge of its structure and function remains far from complete. This is an important gap in understanding because anatomical connectivity is a key determinant of cerebellar function. This chapter focuses on recent advances in understanding the anatomi...
Article
The present study uses a double retrograde tracer technique in rats to examine the spatial localization and pattern of axonal branching in mossy fibres arising from three major sources in the medulla-the external cuneate nucleus, the sensory trigeminal nucleus and the reticular formation, to two electrophysiologically-identified parts of the cerebe...
Article
Full-text available
A key organisational feature of the cerebellum is its division into a series of cerebellar modules. Each module is defined by its climbing input originating from a well-defined region of the inferior olive, which targets one or more longitudinal zones of Purkinje cells within the cerebellar cortex. In turn, Purkinje cells within each zone project t...
Article
Full-text available
In the present study, a non-pulsatile arterially perfused hindbrain and upper body rat preparation is described which is an extension of the brainstem preparation reported by Potts et al., (Brain Res Bull 53(1):59-67), 1. The modified in situ preparation allows study of cerebellar function whilst preserving the integrity of many of its interconnect...
Article
Complex spike synchrony is thought to be a key feature of how inferior olive climbing fibre afferents make their vital contribution to cerebellar function. However, little is known about whether the other major cerebellar input, the mossy fibres (which generate simple spikes within Purkinje cells, PCs), exhibit a similar synchrony in impulse timing...