Cerebellum

From vestibular ganglion (1st neuron) Some terminate directly on *flocculonodular lobe* of the cerebellum Most terminate on the vestibular nuclei

Vestibular nerves

Precise, graded, spatial, and temporal related information about motor activity (firing rate of 70/sec, simple spikes, Na+ channel) Have to be summated (more easily modified)

What kind of information do mossy fibers provide?

Molecular layer (where their dendrites are located) Input from climbing fibers (from inferior olivary nucleus) and parallel fibers (from granule cells of cerebellar cortex)

What layer do Purkinje cells receive input in?

*Red nucleus* (motor for arms) and *thalamus* (projects to cerebral cortex) via the *dentate-rubro-thalamic tract* (or *dentatorubrothalamic tract*) The dentate nucleus is the most lateral nucleus, therefore it makes sense that it is responsible for lateral distal musculature fine motor control

Where does the dentate nucleus project to?

More than the rest of the brain combined

# neurons in cerebellum

Vermis

Midline structure of cerebellum

Dentate nucleus

Output of cerebrocerebellum

Many project to the *flocculonodular lobe* of the cerebellum (Archicerebellum) and the *vermis* via the *inferior cerebellar peduncle* as *mossy fibers* Vestibular nuclei also project to the *fastigial nucleus* (which also receives input from the flocculonodular lobe)

Axons from medial and inferior vestibular nuclei

Decomposes into its parts - *decomposition of movement*

Cerebellar damage - what happens to learned skill?

Regulation and coordination of movement (all aspects of cortex project to cerebellum) Portions of cerebral cortex which control movement project to *pontine nuclei* via the *corticopontine fibers*.

Cerebral cortex communication with cerebellum

From inferior olivary nucleus with branch to deep nuclei (early excitation) and another branch to a Purkinje cell (output from Purkinje cell causes late inhibition of the deep nuclei)

Climbing fibers source and branching

Highly conserved neuronal circuitry across vertebrate species (can survive if born without a cerebellum - it is important but it is a *supporting* structure)

Conservation/importance of cerebellum

Projects to the vestibular and reticular nuclei which project to brainstem motor pathways (UMN axons)

Fastigial nucleus projections

Precise, coordinated movements of the extremities, especially UE

Function of cerebrocerebellum

Axial and lower extremity movements - gait and station

Function of spinocerebellum

Eye movements, neck and trunk movements (Vestibular - where head is in 3D space, cerebellum - where body is in 3D space)

Function of vestibulocerebellum

Receive input from vestibular nuclei Synapse on Purkinje cells which project to the *fastigial nucleus*

Granule cells in flocculonodular lobe

Widespread input to inferior olive from all sensory and motor systems plus from the deep cerebellar nuclei Back up to cerebellum via climbing fibers (climbing fibers wrap around Purkinje cell like "climbing vine")

How does sensory and motor information return to the cerebellum?

Convey unconscious propioceptive information from spinal cord to cerebellum which is used to regulate muscle tone and balance

Information carried by spinocerebellar pathways

Dentate nucleus of the cerebellum Projects to premotor cortex

Input to and projections from ventral lateral nucleus of the thalamus

Pontine nuclei, inferior olive

Input to cerebrocerebellum

Unconscious propioception from DRGs via spinocerebellar tracts, inferior olive

Input to spinocerebellum

Vestibular ganglion, vestibular nuclei, inferior olive

Input to vestibulocerebellum

Three layers: 1. *Molecular layer* (stellate cells, basket cells, Purkinje cell dendrites, parallel fibers from granule cells, climbing fibers from inferior olivary nucleus) 2. *Purkinje cell layer* (cell bodies of Purkinje cells, long axons that project from cerebellar cortex to deep nuclei of cerebellum) 3. *Granule cell layer* (cell bodies of granule cells, axons stay in cerebellar cortex) Above molecular layer = external granule cell layer in newborns (where granule cells are located at birth), in adults = subarachnoid space

Layer of Cerebellar Cortex

From vestibular, spinal cord, and pontine nuclei with one branch to the deep nuclei and the other to granule cells (from granule cells to Purkinje cells by way of parallel fibers)

Mossy fibers source and projections

DRG neurons have peripheral processes that innervate propioceptors in the legs and axons that enter the spinal cord and terminate on spinal border cells

Neuron 1 Anterior spinocerebellar tract system (ASCT)

DRG neurons have peripheral processes that innervate propioceptors in the arms and axons that enter the spinal cord, travel ipsilaterally in the fasciculus cuneatus and terminate in the lateral cuneate nuclei (accessory cuneate nuclei) located in the medulla

Neuron 1 Cuneocerebellar tract system (CCT)

DRG neurons have peripheral processes that innervate propioceptors in the legs and axons that enter the spinal cord, travel ipsilaterally in the fasciculus gracilis and terminate in Clarkes' nucleus

Neuron 1 Posterior Spinocerebellar Tract (PSCT)

Cell bodies in the spinal cord (*T12 to L5*) have axons that cross to the CL side and ascend as the ASCT to the pons where they will cross again and enter the cerebellum via the superior cerebellar peduncle and then terminate on granule cells of the cerebellar cortex Axons of ASCT which terminate on granule cells are one type of mossy fiber

Neuron 2 ASCT

Cell bodies in the lateral cuneate nuclei give rise to axons that travel in the cuneocerebellar tract that travels to the cerebellum via the inferior cerebellar peduncle to terminate on granule cells of the cerebellar cortex. The axons of the CCT that terminate on granule cells are one type of mossy fiber.

Neuron 2 CCT

Cells in Clarkes' nuclei (*T1-L2*)

Neuron 2 PSCT

Granules cells of cerebellar cortex

Neuron 3 ASCT

Granule cells of the cerebellar cortex

Neuron 3 CCT

Granule cells of cerebellar cortex

Neuron 3 PSCT

Fastigial nucleus (vermis), globose and emboliform nuclei (paravermis)

Output from spinocerebellum

Vestibular nuclei

Output from vestibulocerebellum

Granule cells in vermis and paravermis project to Purkinje cells which then project to *globose* and *emboliform* nuclei (collectively, the *interposed nuclei*) These nuclei project to the *red nucleus*

Pathway of information beginning in vermis and paravermis

Pontine nuclei (receiving input from cerebral cortex) project to contralateral granule cells in the lateral portions of the cerebellar hemispheres (neocerebellum) via the *pontocerebellar fibers* and the *middle cerebellar peduncle* Granule cells project to *Purkinje cells* which project to *dentate nucleus* Dentate nucleus projects to contralateral *ventral lateral* (VL) nucleus of the thalamus via the *superior cerebellar peduncle* and the *dentatorubrothalamic tract* (the interposed nuclei project to the red nucleus via this same tract)

Pontine nuclei projections, pathway

Error detection (increase firing when there is an error), complex spike, causes the Purkinje cell to be less responsive to parallel fibers that fired at the same time as the complex spike - Long Term Depression (LTD) Correctional modification

Purpose of climbing fiber signaling in cerebellar "learning"

*Motor learning* (LTD and Ca+) and *error detection* (complex spikes, increased firing from 1-2/sec to 4-6/sec when error is detected) Helps fine tune system if it makes an error (error correction)

Purpose of climbing fibers

Fine tuning Purkinje cells, simple spikes, firing close together, Long Term Potentiation (LTP) The hippocampus uses LTP and LTD

Purpose of parallel fiber signaling in cerebellar "learning"

Important for motor coordination and sensory coordination and processing - it integrates, compares, refigures output May play a role in short-term memory, attention, impulse control, emotion, cognition, task planning, even in such conditions as schizophrenia and autism *Timing*!! Motor memory and learning Receives info from most of the sensory systems and from virtually all other components of the limb and eye movement systems Compares information about the intention of an upcoming movement by receiving info from motor pathways with what actually occurs by retrieving from sensory systems

Roles of cerebellum

Huge - second only to cerebral cortex

Size of cerebellum

Primarily to vermis and adjacent paravermis (paleocerebellum)

Spinocerebellar input

1,128 sq cm (the surface area of the cerebral cortex is 1,900 sq cm)

Surface area of cerebellum

Each granule cell receives synapses from *4 mossy fibers*. Each Purkinje cell receives about *80,000 synapses* from parallel fibers. Therefore each Purkinje cell could receive information from *320,000 mossy fibers*.

Synaptic convergence on Purkinje cells

One mossy fiber branches to *600 granule cells*, each granule cell via parallel fibers synapses with *1,000 Purkinje cells* Therefore, one mossy fiber could contribute to the excitement of *600,000 Purkinje cells*

Synaptic divergence from mossy fibers

1. *Vestibulocerebellum* (Archicerebellum) - Flocculonodular lobe (eye movements, neck and trunk movements) 2. *Spinocerebellum* (Paleocerebellum) - Vermis and Paravermis (axial and lower extremity movements - gait and station) 3. *Cerebrocerebellum* (Neocerebellum) - lateral portion of cerebellar hemispheres (precise, coordinated movements of the extremities, especially UE)

Three main functional subdivisions of the cerebellum

Cortex and deep nuclei

Two main parts of cerebellum

Climbing fibers (from inferior olive) Reticulocerebellar fibers Vestibulocerebellar fibers Cuneocerebellar fibers Posterior spinocerebellar fibers

What are the input fibers to the cerebellum via the Inferior Cerebellar Peduncle (ICP)?

Timing The cerebellum fine tunes the force of muscle movement simultaneously and sequentially across multiple joints to produce smooth flowing, goal directed movement. The elements of *ataxia* are from a fundamental defect in control of force and the exact timing of the starting and stopping movements (result = *dysmetria* - over and under shooting of goal directed movement)

What is the structure and function of the cerebellum designed for? How does cerebellar dysfunction lead to ataxia?

Thoracic spinal cord ASCT

What part of the spinal cord is this?

Circled area: nodulus Cutting in midline - therefore this is a view of the vermis

What portion of the cerebellum is visible?

Purkinje cell axons Mossy fibers and climbing fibers also have collateral projections to deep nuclei

What projects to deep nuclei

Vestibulocerebellum and spinocerebellum --> feedback loops Cerebrocerebellum --> feed-forward loop

What type of loops does the cerebellum form?

Procedural memory (i.e. learning how to ride a bike) When learned, motor acts are no longer consciously thought about but automatic and subconscious

What type of memory is involved with motor learning?

Deep cerebellar nuclei

Where do Purkinje cells project to?

On granule cells

Where do mossy fibers terminate?

*Contralateral* Purkinje cells of the cerebellum via the *Inferior Cerebellar Peduncle* (*ICP*) as *climbing fibers* (wrap around dendrites of Purkinje cells) Another name for ICP = restiform body

Where does the inferior olivary nucleus project to?