The Cerebellum Little Brain Neuroscience Lecture Dr. Laura Georgescu
Learning Objectives 1. Describe functional anatomy of the cerebellum- its lobes, their input and output connections and their functions. 2. Draw and label the circuitry of the cerebellum cortex, assign the functional role of each neuron type and give its synaptic action (excitatory/inhibitory). 3. Describe what is known about the role of the cerebellum in the regulation of skilled movement and in motor learning. 4. Explain servo-control mechanisms as a model for cerebellar regulation of movements. 5. Predict the neurological disturbances that can result from disease or damage in different regions of the cerebellum.
Introduction The basal ganglia and cerebellum modify movement on a minute to minute basis. The motor cortex sends information to both, and both structures send information back via the thalamus (no direct projections to lower motor neurons of skeletal muscles) The balance between these two systems allows for smooth, coordinated movement, and a disturbance in either system will show up as movement disorders.
The Cerebellum Cerebellum (Latin, little brain)= little brain 10 % total volume of the brain but more than half of all its neurons. Arranged in a highly regular manner as repeating units but with input and outputs from virtually all motor cortical regions as well as the spinal cord (in particular proprioceptive input) the cerebellum is provided with extensive information (40 times more axons project into the cerebellum than exit from it) the cerebellum is not necessary to basic elements of perception or movement. damage to the cerebellum disrupts the spatial accuracy and temporal coordination of movement. It impairs balance and reduces muscle tone and motor learning and certain cognitive functions.
Functions of the Cerebellum Maintenance of balance and posture. Through its input from vestibular receptors and proprioceptors, it modulates commands to motor neurons Coordination of voluntary movements. Most movements are composed of a number of different muscle groups acting together in a temporally coordinated fashion Motor learning. The cerebellum - a major role in adapting and finetuning motor programs to make accurate movements through a trial-and-error process (e.g., learning to hit a baseball). Cognitive functions. Involved in certain cognitive functions - language. Thus, like the basal ganglia, the cerebellum is historically considered as part of the motor system, but its functions extend beyond motor control in ways that are not yet well understood.
The Cerebellum Shape: Oval shaped, with an approximate weight of 150 gm Location: Situated in the posterior cranial fossa, dorsal to the pons and medulla, separated from the overlying cerebral cortex by a tough flap in the dura, the cerebellar tentorium Outer mantle of grey matter Internal layer of white matter that contain deep nuclei
Cerebellum - General view Gross features of the cerebellum, including the nuclei, cerebellar peduncles, lobes, folia, and fissures. (Adapted from Nieuwenhuys et al. 1988) A. Dorsal view. Part of the right hemisphere has been cut out to show the underlying cerebellar peduncles. B. Ventral view of the cerebellum detached from the brain stem. C. Midsagittal section through the brain stem and cerebellum, showing the branching structures of the cerebellum.
Cerebellar Functional Anatomy 1. Vestibulocerebellum (flocculo-nodular lobe)- lateral vestibular nuclei- Control of eye & head movements, postural maintenance 2. Spinocerebellum (vermis and intermediate zone) - fastigial and interposed nuclei - Control of limbs and trunk, adaptative motor coordination 3. Cerebrocerebellum (lateral zones)- dentate nuclei Planning and timing of movement+ cognitive functions
The Cerebellum - Three Functionally Distinct Regions
The Cerebellum - Three Functionally Distinct Regions The three functional regions of the cerebellum have different inputs and outputs.
Input-output Organization. Cerebellar nuclei. Cerebellar cortex Deep Cerebellar Nuclei: Fastigial Interposed Dendate + + Cortex - Nuclei + Output Vestibular nuclei Extrinsic inputs: mossy fiber climbing fiber All outputs from the cerebellum originate from the cerebellar deep nuclei. Thus, a lesion to the cerebellar nuclei has the same effect as a complete lesion of the entire cerebellum.
Input and output pathways of the The cerebellar deep nuclei are the sole outputs of the cerebellum All cerebellar nuclei and all regions of cerebellum get special inputs from the inferior olive of the medulla The anatomical locations of the cerebellar nuclei correspond to the cerebellar cortex regions from which they receive input. The medially located fastigial nucleus receives input from the medially located vermis; the slightly lateral interposed nuclei receive input from the slightly lateral intermediate zone The most lateral dentate nucleus receives input from the lateral hemispheres. cerebellum.
Functional organization of cerebellum Cerebellar peduncles = Three fiber bundles carry the input and output of the cerebellum. 1. The inferior cerebellar peduncle (also called the restiform body) primarily contains afferent fibers from the medulla, as well as efferents to the vestibular nuclei. 2. The middle cerebellar peduncle (also called the brachium pontis) primarily contains afferents from the pontine nuclei. 3. The superior cerebellar peduncle (also called the brachium conjunctivum) primarily contains efferent fibers from the cerebellar nuclei, as well as some afferents from the spinocerebellar tract.
Functional organization of cerebellum All output is via the deep nuclei except flocculonodular lobe which outputs via lateral and medial vestibular nuclei. 40 times more input than output fibres Cerebellar lesions lead to ipsilateral symptoms because of a double crossing of the output fibres The cerebellum projects to the contralateral motor cortex, via the thalamus, and the corticospinal pathway recrosses the midline at the lower medulla
Histology and Connectivity of Cerebellar Cortex The cerebellar cortex is divided into three layers The innermost layer, the granule cell layer, is made of 5 x 10 10 small, tightly packed granule cells. The middle layer, the Purkinje cell layer, is only 1-cell thick. The outer layer, the molecular layer, is made of the axons of granule cells and the dendrites of Purkinje cells, as well as a few other cell types. The Purkinje cell layer forms the border between the granule and molecular layers.
Connectivity The cerebellar cortex has a relatively simple, stereotyped connectivity pattern that is identical throughout the whole structure. Cerebellar input can be divided into two distinct classes: 1. Mossy fibers originate in the pontine nuclei, the spinal cord, the brainstem reticular formation, and the vestibular nuclei, and they make excitatory projections onto the cerebellar nuclei and onto granule cells in the cerebellar cortex. They are called mossy fibers because of the tufted appearance of their synaptic contacts with granule cells. 2. Climbing fibers originate exclusively in the inferior olive and make excitatory projections onto the cerebellar nuclei and onto the Purkinje cells of the cerebellar cortex. They are called climbing fibers because their axons climb and wrap around the dendrites of the Purkinje cell like a climbing vine.
Neurons in the Cerebellar Cortex Are Organized into Three Layers
Geometrical Plan of Parallel and Climbing Fibers The geometry of the mossy and parallel fiber system contrasts with that of the climbing fiber system. Mossy fibers excite granule cells whose parallel fibers branch transversely to excite hundreds of Purkinje cells several millimeters from the branch point, both medially and laterally. By contrast, climbing fibers branch in the sagittal dimension to excite 10 or so Purkinje cells anterior and posterior to the branch point. The transverse connections of the parallel fibers and the sagittal connections of the climbing fibers thus form an orthogonal matrix.
Neurons in the Cerebellar Cortex Are Organized into Three Layers The cerebellar cortex is organized into three layers and contains five types of neurons. A vertical section of a single cerebellar folium, in both longitudinal and transverse planes, illustrates the general organization of the cerebellar cortex. The detail of a cerebellar glomerulus in the granular layer is also shown. A glomerulus is a clear space where the bulbous terminal of a mossy fiber makes synaptic contact with Golgi and granule cells.
Functions of the cerebellum The primary function of the cerebellum is to modulate motor output. It compares what will happen with what is intended to happen and makes adjustments. This is referred to as a feed-forward mechanism
Functions of the cerebellum 1. Smoothening postural and skilled movements resulting from skeletal muscle contraction (including eyeball movements) 2. Comparison of intent and action (ie., errors) and generates corrective signals 3. Motor learning and adaptation plays a role in automating and optimizing behavior
Functions of the cerebellum Feedback systems Reactive Responds to the current state of affairs Depends on sensory signals Feed Forward Systems Anticipatory Depends on sensory information but also through experience Can modify the operation of negative feedback mechanisms Essential for rapid action
Functions of the cerebellum Referred to as a silent area as electrical stimulation produces: No movement No sensation However removal or lesions cause severe motor deficits: Movements become uncoordinated and erratic
Internal circuitry Simple three layer arrangement: 1. Molecular 2. Purkinje 3. Granule Five cell types: 1. Granule Cells (excitatory) 2. Purkinje Cells (output cells) 3. Golgi Cells 4. Basket Cells 5. Stellate Cells (these are all inhibitory)
Internal Circuitry Granule cells Layer (innermost) A very small, densely packed neurons that account for the huge majority of neurons in the cerebellum-10 billion granule cells + interneurons known as Golgi cells These cells receive input from mossy fibers and project to the Purkinje cells Cerebellar glomeruli confluence of mossy fibers on granule cells and golgi cells
Internal Circuitry The Purkinje cell Layer (middle) Consists of Purkinje cell bodies (50-80 micrometers) Purkinje cell is one of the most striking cell types in the mammalian brain. Its apical dendrites form a large fan of finely branched processes that extends into the outer molecular The dendritic tree is almost two-dimensional; looked at from the side, the dendritic tree is flat. All Purkinje cells are oriented in parallel. This arrangement has important functional considerations Axons descend to the deep nuclei Release GABA
Internal Circuitry Molecular Cell Layer (outermost) Parallel fibers axons from granule cells which synapse with Purkinje cells Interneurons basket cells and stellate cells
Internal Circuitry Input to cerebellum is excitatory and via: 1. Mossy fibers 2. Climbing fibers Both inputs go first to the deep nuclei to excite them and then ascend upward into the cerebellum
The Purkinje Cells Receive Excitatory Input From Two Afferent Fiber Systems and Are Inhibited by Three Local Interneurons Synaptic organization of the basic cerebellar circuit module. Mossy and climbing fibers convey output from the cerebellum via a main excitatory loop through the deep nuclei. This loop is modulated by an inhibitory side-loop passing through the cerebellar cortex. This figure shows the excitatory (+) and inhibitory (-) connections among the cell types.
Output from Purkinje neurons through deep nuclei, to: Cerebral cortex Brainstem Spinal cord Output of Purkinje cells is inhibitory. Output of deep nuclei is excitatory Internal Circuitry
Motor circuit
Mossy Fibers Originate from nuclei in the spinal cord and brain stem as well as carrying sensory information from the periphery and cortex Terminate on the dendrites of granule cells and excite Purkinje cells via parallel fibers Each Purkinje cell can receive input from as many as 1 million granule cells
Mossy and Climbing Fibers Encode Peripheral and Descending Information Differently Simple and complex spikes recorded intracellularly from cerebellar Purkinje cells. Complex spikes (right bracket) are evoked by climbing fiber synapses, while simple spikes (left bracket) are produced by mossy fiber input. (From Martinez et al. 1971.) Prolonged depolarization (due to opening of voltage gated calcium channels) with an initial large amplitude spike followed by a high-frequency burst of smalleramplitude action potentialsbelieved to have an important role in motor learning.
Climbing Fibers: Firing Patterns It is believed that, during movement, climbing fibers ( by synapsing with Purkinje cell) provide an error signal that depresses parallel fibers that are active concurrently and generate the simple spikes. This allows the correct movements (without the error) to emerge. It is also supposed to be important for motor learning
Vestibulocerebellum Vestibular organs, Superior colliculus, Striate (visual) cortex, via pons Vestibulocerebellum Vestibular nuclei (lateral & medial) Vestibulospinal / bulbar tracts
Vestibulocerebellum Functions: 1. Coordination of movements of head & eyes 2. Control of axial muscles & limb extensors Maintenance of balance/ posture Lesions: Nystagmus: loss of ability to focus Vertigo: loss of balance Ataxia
Spinocerebellum There are body maps on the cerebellar cortex and deep nuclei. Functions: 1. Control of axial and proximal muscles (ongoing movements) 2. Maintenance of balance 3. Coordination of head & eye movements Lesions: Vermis (spinocerebellum or associated nucleus) lesion: 1. Ataxia - wide gait 2. Titubation (head or truncal tremor)
Spinocerebellum - intermediate Dorsal spinocerebellar tract, ventral spinocerebellar tract- these provide cerebellum with information from the muscle& joint propriocetors Spinocerebellum (intermediate zone) Interposed nucleus (emboliform & globose) 1. Descending Dorsolateral system: Magnocelular red nucleus & rubrospinal tract 2. Motor cortex (distal limb areas) via ventrolateral thalamus
Spinocerebellum Lesions 1. Dysarthria - motor speech disorder 2. Dysmetria - loss of control of movement often characterized by overshooting of undershooting the target - results from loss of the feed-forward anticipatory control of movement
Spinocerebellum Lesions 3. Intention tremor broad coarse tremor that increases as target is aproached 4. Decreased muscle tone in limbs 5. Pendular movement of limbs
Cerebrocerebellum Receives fibers from the motor cortex, premotor cortex via the pontine nuclei Cerebrocerebellum Dentate nucleus 1. Red nucleus sends output to the ipsilateral inferior olivary nucleus which goes back to the cerebellum via the climbing fibers 2. Primary Motor cortex and premotor area via the thalamus
Cerebrocerebellum Functions: 1. Planning, initiation and timing of movements 2. Learning of motor skills 3.? Language Connections to prefrontal cortex (Brocca s area via dentate & thalamus)
Motor learning
Cerebrocerebellum - Lesions Many similar signs as for the spino-cerebellum intermediate zone Dysdiadochokinesia = inability to perform rapid alternating movements especially pronation and supination Decomposition of movement especially involving movement across multiple joints and in the distal limb