The Cerebellum - Neuro3050, Block 4

What is the molecular layer of the cerebellum composed of?

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.

Describe the afferent (input) from mossy fibers in the VERMIS & MEDIAL HEMISPHERE. *Include step-by-step process from mossy fiber input until spinal cord.

The vermis and medial hemispheres receive input from proprioceptors in muscles via nuclei in the spinal cord and brainstem. ---POSITION or TENSION in muscle/tendon. ---also known as "Unconscious proprioception" Mode of Action: 1. Mossy fibers excite cerebellar nuclei and purkinje cells ---(A) excites interposed nuclei ---(B) excites fastigial nuclei ---(C) excites purkinje cells in the vermis ---(D) excites purkinje cells in the vermis (A) MFs excite interposed nuclei. Axons from interposed nuclei travel through the superior cerebellar peduncle to synapse in the red nucleus of VL thalamic nucleus. Axons from the red nucleus or VL thalamic nuclei travel to the spinal cord through the rubrospinal tract OR back to the motor cortex through the thalamocortical axons (B) MFs excite fastigial nuclei. Axons from fastigial nuclei travel through inferior cerebellar peduncle and synapse on the reticular formation. Axons from the reticular formation control motor neurons via the reticulospinal tract. (C) Purkinje cells in the vermis inhibit fastigial nuclei output. (D) Purkinje cells in the medial hemisphere do not have a listed function on the powerpoint slide (?)

What is the function of afferent (input) from mossy fibers to the FLOCCULONODULAR LOBE?

To control balance and equilibrium.

What is the function of afferents (input) from mossy fibers in the VERMIS & MEDIAL HEMISPHERE?

To control muscle tone and muscle synergy. Muscle synergy is the coordination across and between joints.

Explain the outcome of mossy fiber afferents in the VERMIS

VIA THE FASTIGIAL NUCLEI POSTURAL ADJUSTMENTS ACORSS MULTIPLE LIMBS + STABILITY OF TRUNK AND PROXIMAL MUSCLES 1st Order: MFs synapse on & excite cell bodies located in the fastigial nuclei. 2nd order: The axons of cells in the fastigial nuclei course via the ICP and synapse on 3rd order neurons in the reticular formation. 3rd order neurons: Axons in the reticular formation travel to the spinal cord to synapse on interneurons. These interneurons control motor neurons in the reticulospinal tract.

Explain the outcome of mossy fiber afferents in the MEDIAL HEMISPHERE

VIA THE INTERPOSED NUCLEI. ADJUSTING LIMB MOVEMENTS. 1st Order: MFs synapse on & excite cell bodies in the interposed nuclei. 2nd Order: The axons of interposed nuclei cells course via the SCP to the RED N. or VL-THALAMIC N. 3-1 ORDER: The axons from the red nucleus travel through the spinal cord through the rubrospinal tract (motor control pathway). *****This means they inputs effect motor output directly, through the rubrospinal tract. 3-2 ORDER : The axons from the VL-Thalamic N. travel to the motor cortex to modulate motor output.

Neurons in the cerebellar cortex regulate the activity of ___________.

cerebellar nuclear neurons

Describe the appearance of the cerebellar layers (from powerpoint presentation)

(Pial Surface) 1. Molecular cell layer 2. Purkinje cell layer 3. Granule cell layer (very dense population of cells) (White Matter)

NUCLEAR NEURONS - Function - Site of cell bodies - Axon pathway - Site of termination

- Carry output of the cerebellum to brainstem nuclei and motor cortex. Without nuclear neurons, cerebellum has no control over movements. -Within nuclei of the brainstem -From nuclei to MOTOR CORTEX -Terminate in the MOTOR CORTEX

Review: What is the function of the RETICULOSPINAL tract?

- Descend in the ventral medial white matter of spinal cord - Terminate medially and bilaterally to influence trunk + proximal limb muscles - Terminate at multiple levels to coordinate and stabilize movements across different joints. ****The reticulospinal system provides a steady level of motor output to activate postural muscles through the body to hold their position.

GRANULE CELLS - Function - Site of cell bodies - Axon pathway - Site of termination

- Excite Purkinje cells - Cell bodies located in the granule cell layer of the cerebellar cortex -Parallel fibers; intrinsic to the cortex - Within the cerebellar cortex

PURKINJE CELLS - Function - Site of cell bodies - Axon pathway - Site of termination

- Purkinje cells are inhibitory target neurons in the cerebellar nuclei. They are GABAergic. -Their cell bodies are located - Axons leave the cerebellar cortex but do not leave the cerebellum - Terminate in one of the cerebellar nuclei (depending on the sagittal division it is located inside of) *Were the first neuronal cells identified!

Discuss the role that the cerebellum has in autism.

-- Deficits in the brainstem, midbrain, frontal lobe and cerebellum (NOT PSYCHOLOGICAL DISORDER) --Decreased size of vermis (particularly lobes VI & VII) --Cerebellum provides input to motor-attentional areas of brain, such as reticular formation --Cerebellum can be independently activated by attention

Delineate the cerebellar pathway found within the lateral hemisphere

1. Cerebellar Cortex *Cerebro-ponto cerebellum Projects to... 2. Deep cerebellar nuclei *Dentate N. Projects to... 3. Upper motor neurons *to modulate premotor cortex (motor planning) through the VL Thalamus.

Delineate the cerebellar pathway found within the vermis & medial hemisphere

1. Cerebellar Cortex *Spino-cerebellum Projects to... 2. Deep cerebellar nuclei *Interposed and fastigial nuclei Projects to... 3. Upper motor neurons *to modulate motor cortex and brain stem (motor execution)

Delineate the cerebellar pathway found within the flocculonodular lobe

1. Cerebellar Cortex *Vestibulo-cerebellum Projects to... 2. Deep cerebellar nuclei *Fastigial N. Projects to... 3. Vestibular N. *vestibular nuclei give rise to vestibulospinal tract to control lower motor neurons (postural control, balance)

Name the 4 nuclei of the cerebellum

1. Fastigial N. (medial) 2. Globose N. (medial interposed nucleus) 3. Emboliform N. (lateral interposed nucleus) 4. Dentate N. (lateral; largest) FGED

Explain what climbing fibers affect & how they do it.

1. PURKINJE CELLS Course along primary purkinje cell dendrites, giving off varicosities that synapse with primary and secondary dendrites, to STRONGLY EXCITE (using Glutamate) *Sole source: INFERIOR OLIVARY COMPLEX

Explain what mossy fibers affect & how they do it.

1. PURKINJE CELLS Mossy fibers are excitatory and synapse on granule cells (in the granular layer). This excites the granule cell, which has an axon (aka parallel fiber) that extends to purkinje cells in the molecular layer. The excited granule cell will excite the purkinje cell, thereby promoting its activity. 1st order: Mossy fiber 2nd order: Parallel fiber 3rd order: Purkinje cell 2. BRAINSTEM NUCLEI; VL THALAMUS Mossy fibers give off collaterals to the cerebellar nuclei.

What are the rostro-caudal divisions of the cerebellum? What is their function?

ANATOMICAL divisions defined by the primary fissure. Anterior lobe, posterior lobe, flocculonodular lobe

How do afferents (inputs) generally reach the cerebellum?

Afferents travel from the brainstem and spinal cord to the cerebellum through the INFERIOR or MIDDLE cerebellar peduncle.

Discuss the clinical signs & developmental effects of chronic alcohol use.

CLINICAL SIGNS: Chronic Use: > Gait ataxia (stiff legged gait with small shuffling steps) > Increased tone in extensor muscles (change in the input received by reticular formation and vestibular nuclei, which alters input to motor neurons) Developmental Effects: > Delays in motor development > Problems with fine motor tasks > Tremors > Ataxia

Discuss the neural consequences of chronic alcohol use.

CONSEQUENCES Chronic Use: >Death of pukinje cells in the anterior lobe spinocerebellum. --->Without these cells, brain decreases levels of cGMP, changing cellular metabolism and function

**Review Describe the course and function of the RUBROSPINAL TRACT.

Cells of the rubrospinal tract originate in the red nucleus, where it receives input from cerebellum and cortex to modulate activity of motor neurons in the spinal cord. Axons cross midline at form RST in the midbrain. Neurons of RST terminate in cervical spinal cord, but some will traverse the entire length of the spinal cord. The rubrospinal tract is an alternative route for cortex to influence alpha motor neurons.

Differentiate cerebellar cortex, cerebellar nuclei, and cerebellar peduncles. *General anatomic location

Cortex: outer layer Nuclei: located within the white matter core Peduncles: white matter tracts near center of cerebellum

Which cerebellar nuclei align with the lateral hemispheres? What is their function?

Dentate nuclei Function: primarily involved in modulating motor planning (through upper motor neurons that project to the VL Thalamus)

Discuss mechanism of impact of ethanol on the cerebellum.

Ethanol augments Cl- channel behavior (opening/closing) in response to GABA. This causes hyperpolarization of purkinje cells in the ANTERIOR LOBE SPINOCEREBELLUM

What are the sagittal divisions of the cerebellum?

FUNCTIONAL divisions. Vermis, medial hemisphere, lateral hemisphere

Which cerebellar nuclei align with the vermis? What is their function (2)?

Fastigial Nuclei (bilateral) Two functions: 1. Involved in modulating motor execution, innervate motor cortex and brainstem 2. Involved in modulating postural control and balance through the vestibular system (innervate the vestibular nuclei, which gives rise to vestibulospinal tract)

What is the function of afferents (input) from mossy fibers in the LATERAL HEMISPHERE?

Fine coordination of movement; planning and controlling movement, especially distally.

Describe function of ICP

ICP connects the spinal cord and medulla to the cerebellum. Mainly an input pathway; small output pathway from the cerebellum.

Are mossy fiber afferents relaying direct or indirect input from the cerebral cortex?

Indirect; neurons in the cortex synapse on neurons in the basilar pons -- neurons in the basilar pons cross the midline and project to the lateral part of the cerebellum [via mossy fibers]

Which cerebellar nuclei align with the medial hemispheres? What is their function?

Interposed nuclei ---Globose N. (medial interposed nucleus) ---Emboliform N. (lateral interposed nucleus) Function: primarily involved in modulating motor execution, innervate motor cortex and brainstem

Describe function of MCP

MCP connects the pons to the cerebellum. Largest peduncle. Exclusively an input pathway. Pathway crosses in the pons.

How is "music food for the brain?

Male musicians have a cerebellum that is ~5% larger than controls. Theory: Many years of precise finger exercise stimulated extra neural growth in the cerebellum.

What are the 2 major afferent systems to the cerebellum?

Mossy Fibers & Climbing Fibers

How are MOSSY FIBERS and CLIMBING FIBERS morphologically distinct?

Mossy fibers are complex and have large terminals. Climbing fibers outline the primary and secondary dendrites of purkinje cells.

What is the overarching function of neurons in the cerebellar cortex? Where do they project to?

Neurons in the cerebellar cortex regulate the activity of cerebellar nuclear neurons.

Are the cerebellar nuclei sites of INPUT or OUTPUT of the cerebellum? Where do their axons terminate?

Neurons in the cerebellar nuclei are the output neurons of the CEREBELLUM. Their axons leave the cerebellum to terminate in brainstem nuclei that in turn innervate neurons in the spinal cord or cerebral cortex.

What is the most primitive part of the brain?

On the inferior view, a third very small lobe is defined as the FLOCCULONODULAR lobe; most primitive part of the cerebellum.

What is/are the origin(s) of CLIMBING FIBERS?

Origin of CLIMBING FIBERS: - Inferior olive

What is/are the origin(s) of MOSSY FIBER AFFERENTS?

Origin of MOSSY FIBERS: - Vestibular Nuclei - Pontine Nuclei - Spinal Cord - Reticular Formation

What is the function of cerebellar peduncles? Name and describe the three the cerebellar peduncles.

Peduncles are fiber tract that connect the cerebellum to the brainstem. Superior Cerebellar Peduncle: ---SCP connects the cerebellum to the midbrain and diencephalon. Axons leaving the cerebellum cross in the midbrain. Major output pathway from the cerebellum to the brainstem. Middle Cerebellar Peduncle: --MCP connects the pons to the cerebellum. Largest peduncle. Exclusively an input pathway. Pathway crosses in the pons. Inferior Cerebellar Peduncle: --ICP connects the spinal cord and medulla to the cerebellum. Mainly an input pathway; small output pathway from the cerebellum.

Describe the proposed function of the climbing fiber input to the cerebellum.

Play a role in error detection Input to the inferior olivary complex: SPINAL CORD CEREBRAL CORTEX VESTIBULAR NUCLEI RED NUCLEUS RETICULAR FORMATION CEREBELLUM "All around" feedback; explains reason for strong impact on purkinje cells

Explain how mossy fiber input to the vermis/medial hemisphere affects muscle tone and synergy VIA THE LATERAL HEMISPHERE

Pre-1st order: Cortex neurons synapse on basilar pons neurons. Basilar pons neurons **cross the midline** and project to cerebellum [via MFs] 1st order: MFs excite cell bodies located in the dentate nuclei. 2nd order: Cell bodes in the dentate nuclei synapse in on cell bodies in the VA/VL thalamic nuclei. 3rd order: Cell bodies in the VA/VL thalamic nuclei project to the motor cortex to influence the corticospinal tract HOWEVER..... Purkinje cells in the lateral hemisphere synapse on neurons in the dentate nuclei to INHIBIT THEM.

Describe function of SCP

SCP connects the cerebellum to the midbrain and diencephalon. Axons leaving the cerebellum cross in the midbrain. Major output pathway from the cerebellum to the brainstem.

Where does the input to the inferior olivary complex come from?

SPINAL CORD CEREBRAL CORTEX VESTIBULAR NUCLEI RED NUCLEUS RETICULAR FORMATION CEREBELLUM

General layout of spinocerebellar homunculus (motor!)

See photo

What forms the border between the granule and molecular layer?

The Purkinje cell layer forms the border between the granule and molecular layers.

What does the cerebellum "act" as? How is it connected to other structures within the CNS? *name all 5 connections (2 input, 3 output)

The cerebellum acts as a COMPARATOR. Connections (1) TO brainstem nuclei, which relay to the spinal cord (2) TO Thalamus, which relays to the cerebral cortex (3) FROM pons, which relays from the cortex (4) FROM brainstem nuclei (5) FROM muscle [unconscious pathway]

Describe the afferent (input) from mossy fibers in the FLOCCULONODULAR LOBE. *Include step-by-step process from mossy fiber input until spinal cord.

The flocculonodular lobe receives input from the VESTIBULAR SYSTEM through mossy fiber afferents that travel through the INFERIOR CEREBELLAR PEDUNCLE. Mode of Action: 1. Mossy fibers excite purkinje cells in the flocculonodular lobe 2. Purkinje cells in the flocculonodular lobe inhibit neurons in the fastigial nucleus. 3. Fastigial axons leaving the fastigial nucleus, now inhibited, will no longer excite neurons in the vestibular nuclei. 4. Inhibited vestibular nuclei axons that travel through the vestibulospinal tracts will no longer excite interneurons that regulate activity of the alpha & gamma motor neurons in the ventral horn of the spinal cord.

Describe the basic functions of the cerebellum. *note: there are 6 functions

The functions of the cerebellum are... 1. Control posture and balance 2. Coordinate sequential movements 3. Coordinate rapidly alternating movements 4. Regulate Reflexes 5. Involved in motor learning ---Execute complex, smooth pursuit eye movements 6. Higher cognitive function (attention, planning movement)