Cerebellar mossy fiber

About: Cerebellar mossy fiber is a research topic. Over the lifetime, 96 publications have been published within this topic receiving 13379 citations.

A Theory of Cerebellar Cortex

Abstract: 1. A detailed theory of cerebellar cortex is proposed whose consequence is that the cerebellum learns to perform motor skills. Two forms of input-output relation are described, both consistent with the cortical theory. One is suitable for learning movements (actions), and the other for learning to maintain posture and balance (maintenance reflexes). 2. It is known that the cells of the inferior olive and the cerebellar Purkinje cells have a special one-to-one relationship induced by the climbing fibre input. For learning actions, it is assumed that: (a) each olivary cell responds to a cerebral instruction for an elemental movement. Any action has a defining representation in terms of elemental movements, and this representation has a neural expression as a sequence of firing patterns in the inferior olive; and (b) in the correct state of the nervous system, a Purkinje cell can initiate the elemental movement to which its corresponding olivary cell responds. 3. Whenever an olivary cell fires, it sends an impulse (via the climbing fibre input) to its corresponding Purkinje cell. This Purkinje cell is also exposed (via the mossy fibre input) to information about the context in which its olivary cell fired; and it is shown how, during rehearsal of an action, each Purkinje cell can learn to recognize such contexts. Later, when the action has been learnt, occurrence of the context alone is enough to fire the Purkinje cell, which then causes the next elemental movement. The action thus progresses as it did during rehearsal. 4. It is shown that an interpretation of cerebellar cortex as a structure which allows each Purkinje cell to learn a number of contexts is consistent both with the distributions of the various types of cell, and with their known excitatory or inhibitory natures. It is demonstrated that the mossy fibre-granule cell arrangement provides the required pattern discrimination capability. 5. The following predictions are made. (a) The synapses from parallel fibres to Purkinje cells are facilitated by the conjunction of presynaptic and climbing fibre (or post-synaptic) activity. Reprinted with permission of The Physiological Society, Oxford, England. (b) No other cerebellar synapses are modifiable. (c) Golgi cells are driven by the greater of the inputs from their upper and lower dendritic fields. 6. For learning maintenance reflexes, 2(a) and 2 (b) are replaced by 2’. Each olivary cell is stimulated by one or more receptors, all of whose activities are usually reduced by the results of stimulating the corresponding Purkinje cell. 7. It is shown that if (2’) is satisfied, the circuit receptor → olivary cell → Purkinje cell → effector may be regarded as a stabilizing reflex circuit which is activated by learned mossy fibre inputs. This type of reflex has been called a learned conditional reflex, and it is shown how such reflexes can solve problems of maintaining posture and balance. 8. 5(a), and either (2) or (2’) are essential to the theory: 5(b) and 5(c) are not absolutely essential, and parts of the theory could survive the disproof of either.

A Theory of Cerebellar Function

Abstract: A comprehensive theory of cerebellar function is presented, which ties together the known anatomy and physiology of the cerebellum into a pattern-recognition data processing system. The cerebellum is postulated to be functionally and structurally equivalent to a modification of the classical Perceptron pattern-classification device. It is suggested that the mossy fiber → granule cell → Golgi cell input network performs an expansion recoding that enhances the pattern-discrimination capacity and learning speed of the cerebellar Purkinje response cells. Parallel fiber synapses of the dendritic spines of Purkinje cells, basket cells, and stellate cells are all postulated to be specifically variable in response to climbing fiber activity. It is argued that this variability is the mechanism of pattern storage. It is demonstrated that, in order for the learning process to be stable, pattern storage must be accomplished principally by weakening synaptic weights rather than by strengthening them.

Cerebellar Cortex: Cytology and Organization

Abstract: I. Introduction.- 1. A New Morphology.- 2. The Fiber Connections of the Cerebellar Cortex.- 3. The Design of the Cerebellar Cortex.- II. The Purkinje Cell.- 1. A Little History.- 2. The Soma of the Purkinje Cell.- 3. The Nucleus.- a) The Chromatin.- b) The Nucleolus.- 4. The Perikaryon of the Purkinje Cell.- a) The Nissl Substance.- b) The Agranular Reticulum.- c) The Hypolemmal Cisterna.- d) The Golgi Apparatus.- e) Lysosomes.- f) Mitochondria.- g) Microtubules and Neurofilaments.- 5. The Dendrites of the Purkinje Cell.- a) The Form of the Dendritic Arborization.- b) Dendritic Thorns.- High Voltage Electron Microscopy of Dendritic Thorns.- c) The Fine Structure of Dendrites and Thorns.- 6. The Purkinje Cell Axon.- a) The Initial Segment.- b) The Recurrent Collaterals.- c) The Terminal Formations of the Collaterals.- Synaptic Relations of the Recurrent Collaterals.- Purkinje Cell Axon Terminals in the Central Nuclei.- 7. The Neuroglial Sheath.- 8. Some Physiological Considerations.- 9. Summary of Intracortical Synaptic Connections of Purkinje Cells.- III. Granule Cells.- 1. The Granule Cell in the Optical Microscope.- a) Some Numerical Considerations.- 2. The Granule Cell in the Electron Microscope.- a) The Nucleus.- b) The Perikaryon.- c) The Dendrites of Granule Cells.- d) The Ascending Axons of Granule Cells.- e) Ectopic Granule Cells.- f) Parallel Fibers.- 3. Summary of Synaptic Connections of Granule Cells.- IV. The Golgi Cells.- 1. A Little History.- 2. The Large Golgi Cell.- a) The Form of the Large Golgi Cell.- b) The Fine Structure of Large Golgi Cells.- The Perikaryon of Large Golgi Cells.- The Dendrites of Large Golgi Cells.- The Axonal Plexus of the Goigi Cell.- 3. The Small Goigi Cell.- a) The Fine Structure of Small Goigi Cells.- b) The Synapse en marron.- c) The Dendrites and Axons.- 4. Summary of Synaptic Connections of Golgi Cells.- V. The Lugaro Cell.- 1. A Little History.- 2. The Lugaro Cell in the Light Microscope.- 3. Fine Structure of the Lugaro Cel.- 4. Summary of Synaptic Connections of Lugaro Cells.- VI. The Mossy Fibers.- 1. A Little History.- 2. The Mossy Fiber in the Light Microscope.- 3. The Glomerulus.- a) The History of a Concept.- b) The Fine Structure of the Glomerulus.- The Form of the Mossy Fiber Terminal.- The Core of the Mossy Fiber.- The Synaptic Vesicles.- The Granule Cell Dendrites.- The Golgi Cell Axonal Plexus.- The Protoplasmic Islet.- 4. The Identification of Different Kinds of Mossy Fibers.- 5. Summary of Intracortical Synaptic Connections of Mossy Fibers.- VII. The Basket Cell.- 1. A Little History.- 2. The Form of the Basket Cell and Its Processes.- a) The Dendrites.- b) The Axon and Its Collaterals.- 3. The Fine Structure of the Basket Cell.- a) The Perikaryon.- b) The Dendrites.- c) The Axon.- The Pericellular Basket.- The Pinceau.- The Neuroglial Sheath.- 213.- 4. Summary of Synaptic Connections of Basket Cells.- VIII. The Stellate Cell.- 1. A Little History.- 2. The Stellate Cell in the Light Microscope.- a) The Superficial Short Axon Cell.- b) The Deeper Long Axon Stellate Cell.- c) The Difference between Stellate and Basket Cells.- 3. The Fine Structure of the Stellate Cell.- a) The Cell Body.- The Cytoplasm.- b) The Dendrites.- c) The Axon.- 4. Some Physiological Considerations.- 5. Summary of Synaptic Connections of Stellate Cells.- IX. Functional Architectonics without Numbers.- 1. The Uses of Inhibition.- a) Basket Cells.- b) Stellate Cells.- c) Golgi Cells.- d) Purkinje Cells.- 2. The Shapes of Synaptic Vesicles.- 3. A Hitherto Unrecognized Fiber System.- 4. The Inhibitory Transmitter.- X. The Climbing Fiber.- 1. A Little History.- 2. The Climbing Fiber in the Optical Microscope.- a) The Immature Climbing Fiber Plexus.- 3. The Climbing Fiber in the Electron Microscope.- a) The Terminal Arborization in the Molecular Layer.- The Functional Significance of the Climbing Fiber Arborization.- The Advantages of Thorn Synapses.- Relationships with Basket and Stellate Cells.- b) The Climbing Fiber and Its Collaterals in the Granular Layer.- The Climbing Fiber Glomerulus.- The Climbing Fiber Synapse en marron.- The Tendril Collaterals in the Granular Layer.- c) The Fine Structure of Climbing Fiber Terminals and Their Synaptic Junction.- 4. The Connections of the Climbing Fiber.- 5. Some Functional Correlations.- 6. Summary of Intracortical Synaptic Connections of Climbing Fibers.- XI. The Neuroglial Cells of the Cerebellar Cortex.- 1. The Golgi Epithelial Cells.- a) A Little History.- b) The Golgi Epithelial Cell in the Optical Microscope.- c) The Golgi Epithelial Cell in the Electron Microscope.- The Perikaryal Processes.- The Bergmann Fibers.- The Subpial Terminals.- 2. The Velate Protoplasmic Astrocyte.- 3. The Smooth Protoplasmic Astrocyte.- 4. The Oligodendrogliocyte.- 5. The Microglia.- 6. Functional Correlations.- XII. Methods.- 1. Electron Microscopy.- a) Equipment for Perfusion of Adult Rats.- b) The Perfusion Procedure.- c) Equipment for the Dissection of Rat Brains for Electron Microscopy.- d) The Dissection Procedure.- e) The Postfixation of Tissue Slabs.- f) In-Block Staining, Dehydration, and Embedding.- g) Solutions and Other Formulas.- h) The Cutting of 1 urn Semithin Sections of Epon-Embedded Cerebellum.- i) Thin Sectioning.- j) The Staining of Thin Sections on Grids.- k) Electron Microscopy.- 2. The Golgi Methods.- a) Introduction.- b) Perfusion Solutions - Freshly Prepared.- c) Procedures for the Golgi Methods.- d) Dehydration and Infiltration of Slabs of Golgi-Impregnated Tissue for Embedding in Nitrocellulose.- 3. High Voltage Electron Microscopy.- a) Embedding and Sectioning of Golgi Material.- b) Counterstaining.- 4. Electron Microscopy of Freeze-Fractured Material.- References.

Integration of quanta in cerebellar granule cells during sensory processing.

Abstract: To understand the computations performed by the input layers of cortical structures, it is essential to determine the relationship between sensory-evoked synaptic input and the resulting pattern of output spikes. In the cerebellum, granule cells constitute the input layer, translating mossy fibre signals into parallel fibre input to Purkinje cells. Until now, their small size and dense packing have precluded recordings from individual granule cells in vivo. Here we use whole-cell patch-clamp recordings to show the relationship between mossy fibre synaptic currents evoked by somatosensory stimulation and the resulting granule cell output patterns. Granule cells exhibited a low ongoing firing rate, due in part to dampening of excitability by a tonic inhibitory conductance mediated by GABA(A) (gamma-aminobutyric acid type A) receptors. Sensory stimulation produced bursts of mossy fibre excitatory postsynaptic currents (EPSCs) that summate to trigger bursts of spikes. Notably, these spike bursts were evoked by only a few quantal EPSCs, and yet spontaneous mossy fibre inputs triggered spikes only when inhibition was reduced. Our results reveal that the input layer of the cerebellum balances exquisite sensitivity with a high signal-to-noise ratio. Granule cell bursts are optimally suited to trigger glutamate receptor activation and plasticity at parallel fibre synapses, providing a link between input representation and memory storage in the cerebellum.

Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses

Abstract: Among the many issues surrounding the involvement of the cerebellum in motor learning, the relative roles of the cerebellar cortex and cerebellar nuclei in Pavlovian conditioning have been particularly difficult to assess. While previous studies have investigated the effects of cerebellar cortex lesions on the acquisition and retention of conditioned movements, we have examined the effects of these lesions on the timing of Pavlovian eyelid responses. The rationale for this approach arises from previous studies indicating that this timing is a component of Pavlovian eyelid responses that is learned and that involves temporal discrimination. To permit within-animal comparisons, rabbits were trained to produce differently timed responses to high- and low-frequency auditory conditioned stimuli (CSs). Before the lesion the conditioned responses to both CSs were appropriately timed--each peaked near the time at which the unconditioned stimulus was presented for that CS. However, after the lesion both CSs could elicit similarly timed conditioned responses that peaked inappropriately at very short latencies. The changes in responses timing were sensitive to the size of the lesion, particularly its rostral-caudal extent. Similar results were obtained in animals trained with one CS, indicating that the disruption of response timing is not related to impaired auditory discrimination. Because response timing is learned and therefore requires synaptic plasticity, these data suggest that there are at least two sites of plasticity involved in the motor expression of Pavlovian eyelid responses. Plasticity at one site is necessary for the learned timing of conditioned responses, while plasticity at another site is revealed by the inappropriately timed responses observed following removal of the cerebellar cortex. This lesion-induced dissociation of the expression of motor responses and their learned timing supports a synthesis of competing views by suggesting that motor learning involves both the cerebellar cortex and cerebellar nuclei. We hypothesize that motor learning involves a decrease in strength of the granule cell-Purkinje cell synapses (e.g., Ito and Kano, 1982) in the cerebellar cortex and an increase in strength of the mossy fiber-cerebellar nuclei synapses (e.g., Racine et al., 1986). Finally, these data suggest that the cerebellar cortex may mediate the temporal discriminations that are necessary for the learned timing of conditioned responses.