The Cerebellum“The Little Brain”

Neuroscience Lecture

PhD Candidate 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, assignthe functional role of each neuron type and give its synapticaction (excitatory/inhibitory)

3. Describe what is known about the role of the cerebellum inthe regulation of skilled movement and in motor learning

4. Explain servo-control mechanisms as a model for cerebellarregulation of movements

5. Predict the neurological disturbances that can result fromdisease 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 corticalregions as well as the spinal cord - in particularproprioceptive input

• The cerebellum is provided with extensive information - 40times more axons project into the cerebellum than exitfrom it

• The cerebellum is not necessary to basic elements ofperception or movement

• Damage to the cerebellum disrupts the spatial accuracyand temporal coordination of movement→ It impairsbalance and reduces muscle tone and motor learning andcertain 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 - a number of different muscle groups acting together in a temporally coordinated fashion

• Motor learning. The cerebellum - a major role in adapting and fine-tuning motor programs to make accurate movements through a trial-and-error process

• 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 - Anatomy

• 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

General view

Gross features of the cerebellum, including the nuclei, cerebellarpeduncles, lobes, folia, and fissures. (Adapted from Nieuwenhuys etal. 1988)A. Dorsal view. Part of the right hemisphere has been cut out toshow 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

3. Cerebrocerebellum (lateral zones)- dentate nuclei –Planning and timing of movement+ cognitive functions

The Cerebellum - Three Functionally Distinct Regions

The three functional regions of the cerebellum have different inputs and outputs.

Functional organization of cerebellumCerebellar peduncles = Three fiber bundles

carry the input and output of the cerebellum.

1. The inferior cerebellar peduncle primarily contains afferent fibers from the medulla, as well as efferents to the vestibular nuclei

2. The middle cerebellar peduncle primarily contains afferents from the pontine nuclei

3. The superior cerebellar peduncle primarily contains efferentfibers from the cerebellar nuclei, as well as some afferents from the spinocerebellar tract.

Histology and Connectivity of Cerebellar CortexSimple three layer

arrangement:1. Molecular2. Purkinje3. Granule

Five cell types:1. Granule Cells

(excitatory)2. Purkinje Cells

(output cells)3. Golgi Cells4. Basket Cells5. Stellate Cells

(these are all inhibitory)

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 fibers

• 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

Input to the cerebellum

Input to the cerebellum

*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

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.

Cerebellar cortexInput to cerebellum is excitatory

and via:

1. Mossy fibers - named because of the tufted appearance of their synaptic contacts with granule cells

2. Climbing fibers – named because their axons climb and wrap around the dendrites of the Purkinje cell like a climbing vine

Both inputs go first to the

deep nuclei to excite

them and then ascend

upward into the

cerebellum

Cerebellar cortex

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.

Geometrical Plan of Parallel and Climbing fibers

The geometry of the mossy and parallelfiber system contrasts with that of theclimbing fiber system. Mossy fibersexcite granule cells whose parallel fibersbranch transversely to excite hundredsof Purkinje cells several millimeters fromthe branch point, both medially andlaterally.

Internal Circuitry1. Granule cells Layer

(innermost)• 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

2. 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

3. Molecular Cell Layer (outermost)

• Parallel fibers – axons from granule cells which synapse with Purkinje cells

• Interneurons – basket cells and stellate cells

The Purkinje Cells Receive Excitatory Input From Two Afferent Fiber Systems and Are Inhibited by Three Local Interneurons

Synaptic organization of the basiccerebellar circuit module. Mossyand climbing fibers convey outputfrom the cerebellum via a mainexcitatory loop through the deepnuclei. This loop is modulated byan inhibitory side-loop passingthrough the cerebellar cortex. Thisfigure shows the excitatory (+) andinhibitory (-) connections amongthe cell types.

Internal Circuitry

Output from Purkinje

neurons through deep

nuclei, to:

• Cerebral cortex

• Brainstem

• Spinal cordOutput of Purkinje cells is

inhibitory

Output of deep nuclei is excitatory

Descending outputs from the cerebellum

Input and output pathways of the cerebellum

The cerebellar deep nuclei = 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.

Ascending outputs from the cerebellum

Functions of the cerebellumThe 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 severemotor deficits:• Movements become uncoordinated and

erratic

Motor circuit

Mossy and Climbing Fibers Encode Peripheral and

Descending Information Differently

Simple and complex spikesrecorded intracellularly fromcerebellar Purkinje cells.Complex spikes (right bracket)are evoked by climbing fibersynapses, while simple spikes(left bracket) are produced bymossy fiber input. (FromMartinez et al. 1971.)

Prolonged depolarization (due toopening of voltage gated calciumchannels) with an initial largeamplitude spike followed by ahigh-frequency burst of smaller-amplitude action potentials.

Climbing Fibers: Firing Patterns

• It is believed that during movement climbing fibers provide an error signal that depresses parallel fibers that are active concurrentently 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

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

Summary of cerebellar organization

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: wide gait

SpinocerebellumThere 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

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 ventrolateralthalamus

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, premotorcortex via the pontine nuclei

Cerebrocerebellum

Dentate nucleus

1. Red nucleus sends output to the ipsilateralinferior 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

Thank you!