Module 18 - Lecture 14 - Cerebellum

Question 1

What are the two primary divisions of the cerebellum and what functional loop is within each.

Answer 1

1. Cerebellar cortex – inhibitory loop
2. Deep Cerebellar nuclei – extitatory loop; origin for most “outputs”

Question 2

In general, what are the types of inputs to the cerebellum?

Answer 2

There are 3 distinct white matter tracts:

1. Superior - efferent - out
2. Middle - afferent - in
3. Inferior - mixed

Question 3

What peduncle are inputs from the cerebral cortex (via pontine nuclei) contained in?

Answer 3

Middle Peduncle

Question 4

What peduncles are input for all inferior brainstem nuclei contained in?

Answer 4

• Inferior Peduncle
  
  • Brainstem:
    
    • Inferior olive
    • CN VIII/vestibular nuclei
    • Spinal cord
      
      • External cuneate N
      • Dorsal N of Clarke
    • Trigeminal complex (mesencephalic N)
    • Visual signals via brainstem pathways (tectopulvinar)

Question 5

What side of the body does the cerebellum (CB) process?

Answer 5

• Ipsilateral side (in contrast to the cerebral cortex which processes information from the contralateral side)
  
  • The superior areas decussate (become ipsilateral) & inferior areas remain ipsilateral.

Question 6

What are the 2 distinct parts of the cerebellum that received inputs?

Answer 6

1. Cerebellar cortex
2. Deep nuclei
   
   1. There is a generic connectivity → these parts are linked via networks to modulate activity of the outputs to UMN targets
   2. There is also specific connectivity → 3 distincts functional CB cortex and DN regions/pairings

Question 7

What are the 3 functional divisions of the cerebellar cortex?

Answer 7

1. Cerebrocerebellum
   
   • Lateral aspect
2. Spinocerebellum
   
   • Medial superior
   • Subdivided into:
     
     • Center = vermis
     • Lateral = paravermis
3. Vestibulocerebellum
   
   • Inferior two regions
     
     • Nodulus
     • Flocculus

Question 8

What are the respective connected “deep nucleus/ nuclei” to the divisions of the cerebral cortex?

Answer 8

• Cerebrocerebellum = dentate nuclei
• Spinocerebellum = 3 medial nuclei:
  
  • Interposed (2)
    
    • Emboliform*don’t need to know
    • Globose*don’t need to know
  • Fastigial

***mnemonic = DON’T EAT GREASY FOOD

• Vestibulocerebellum = vestibular nuclei (in the brainstem NOT the cerebellum)

***The input of the 3 functional divisions of the cerebellar cortex will connect to these regions on the deep nucleus.

Question 9

What movements/ planning is the vestibulocerebellum
part responsible for?

Answer 9

• modifies vestibular reflexes (like VOR) for eye motion (vestibular ocular reflex)
• modifies vestibular reflexes (like VCR VSR) for movements underlying postural control/balance (vestíbulo cervical reflex and vestibular spinal reflex)
• *The primary input of the vestibulocerebellum is the vestibular nuclei, which receives itself a lot of sensory information. Then the vestibulocerebellum, its connectivity will lead to changes/modulation of inhibition of the vestibular nuclei itself, to be able to modify the output of the vestibular nuclei → to contribute its movements

Question 10

What movements/ planning is the spinocerebellum cortex part responsible for?

Answer 10

• Modifies primary motor cortex vis ventral lateral thalamus
• Modifies UMN in the brainstem including the superior colliculus (voluntary eye/neck motion) and the reticular formation (gait & postural control)
• Primary function is to provide postural support to correct for any discrepancies that are occurring during the voluntary movement
  
  • Vermis = proximal/postural muscles
  • Paravermis = distal muscle → modify the primary motor cortex to correct the errors.

Question 11

What movements/ planning is the cerebrocerebellum cortex part responsible for?

Answer 11

• Helps with planning our skilled motion before execution through its connections to the ventral and anterior aspects of the thalamus (lateral goes to primary motor cortex and anterior goes to the secondary motor cortex)
• And also contribute to error correction during the execution of the movement due to its connections to the lateral aspect of the thalamus

Question 12

What is the general the difference of movement processed in the vermis/ paravermis?

Answer 12

Vermis = movement of the proximal muscles 
Paravermis = movement of the distal muscles

Question 13

What is an efference and afferent copy?

Answer 13

• Efference copy – initial feedforward blueprint of intended movement (motor pattern)
  
  • Therefore it can work as an “error check”’, it can be modified via processing in the cerebellum (pre-correction)
• Afferent copy – sensory afferent information received either during or after the movement itself in which acts as feedback to adjust the excitation to the UMN in either real time or after the movement to adjust for errors in the motor program.
  
  • It is essentially a comparison of intended and actual movement
  • Can reduce error via correcting UMN control of movement → real time and offline.

Question 14

What is the importance of the Purkinje Cell? What does it synapse on? Is this synapse excitatory or inhibitory? What are the 2 major inputs to the Purkinje Cell are these excitatory or inhibitory?

Answer 14

• The Purkinje cells synapse on the deep nuclei.
• It is inhibitory (uses GABA)
• The two major inputs to the Purkinje cells are climbing fibres and mossy fibers which are both excitatory.

Question 15

What is the general concepts of the “excitatory loop”?

Answer 15

The axons from the climbing fibers and the mossy fibers both have collaterals that synapse on the deep nuclei - both excitatory (glutaminergic), lead to the excitation of the deep cerebellar nuclei to ultimately excite the UMN.

Question 16

What is the general concepts of the “inhibitory loop”

Answer 16

• Axons from the climbing fibers synapse on the purkinje cells directly.
• Axons from the mossy fibers synapse on the granular cells that also synapse on the purkinje cells. Both of these inputs are EXCITATORY to the purkinje cells however the purkinje cells are INHIBITORY to the deep cerebellar nuclei.
• Therefore, the output of the deep cerebellar nuclei is influenced but how much excitation there is from the “excitatory loop” and also how much inhibition there is from the “inhibitory loop”. The net balance of inhibition and excitation leads to modification of the UMN excitation needed for movement.

Question 17

How does the CB online modify UMN activity? (Influenced by the amount of inhibition from the Purkinje Cells)

Answer 17

• The amount of inhibition from the purkinje cells depends on:
  
  • The synaptic strength varies due to neuroplasticity
  • The amount of convergence/divergence which can modify the summated potential of the Purkinje cell
  • Modifier cells which control the flow of information through the cerebellar cortex

Question 18

What are 3 mechanisms by which the input to the deep nuclei is not the same as the inputs to the Purkinje Cell?

Answer 18

The inputs to the Purkinjie cells depends on the (as mentioned above):

1. Synaptic strength
   
   • Recall the size of an EPSP depends on the # of receptors activated.
   • This can be different on the Deep nuclei or purkinje cell connection → plasticity
2. Spreading thin/integration (convergence and divergence)
   
   • If you follow the journey of the inhibitory loop, the climbing fibers, they will make a 1:1 synapse with the purkinje fibers. Meanwhile, the Mossey fibers are synapsing on the granule cell which becomes highly divergent and spread out a ton of parallel fibers which will then synapse on a variety of purkinje cells
   • *for a single Purkinje –> there is now potentially 200000 input from the previous Mossey fiber that is diverging in the granule cell
   • Potential for modified summation of purkinje cell for gain/error correction
3. Modifiers
   
   • The stellate & Basket cells are going to be inhibitory to the purkinje fibers itself
   • The golgi cells can be inhibitory to the granule cells and the control “gain” of input to purkinje cells by parallel fibers
   • These smaller inhibitory “players” can temporarily influence the ability to summate the purkinje fibers → this group of interneurons control the flow/gain (strength) of information through the cerebellar cortex.

Input to the deep nuclei is the result of the summated potential from all of these inputs and modifications to the purkinje cells leading to a change in inhibition to the deep nuclei. As the cerebellum detects errors in movement there are alterations in the amount of inhibition to the deep nuclei leading to alterations in the movement pattern.

• For simplicity sake
• Initial plan or motor pattern = too much movement is detected → increase inhibition = decrease movement
• Initial plan or motor pattern = too little movement → decrease inhibition = increase movement

Question 19

What are two main impairments associated with olivary neuron damage?

Answer 19

• Impairment of motor adaptation (changes in the gain of excitation or inhibition of UMN in pathways that we are engaged in for a short period of time)
• Impairment of motor learning (harder time changing the way we excite UMN long term)
  
  • Specific mechanism is still unknown → the reason why is because of the convergence and divergence and potential of synapse that could change the relative gain or weight of input sensory or efferent information that comes into the cerebellum itself.
  • Ultimate change in synaptic strength via plasticity modifies relative gain or emphasis of a variety of converging inputs manipulating the summated strength of the purkinje cell summation → inhibitory strength

Question 20

What are the general dysfunctions hallmark by cerebellum damage?

Answer 20

• Discoordination of movement
• Less ability to correct movement errors
• Diminished ability to learn highly skilled sequences
  
  • The dysfunction is ipsilateral to CB damage
  • The damage is not purely motor or sensory
  • In some cases no sensory loss
  • Movement is possible, just not typical

Question 21

What are the typical dysfunctions with cerebellum damage that are dependent on CB cortex area damaged?

Answer 21

• Damage to vestibulocerebellum = dysfunction in eye movements (spontaneous nystagmus)
  
  • Eyes drift from target and then “jump” back with corrective saccade
• Damage to spinocerebellum = difficulty controlling walking movements (wide-based gait)
  
  • Degeneration of anterior portion of cerebellar cortex (ETOH abuse)
• Damage to cerebrocerebellum = difficulty performing “learned” movements (impairment in highly skilled activity) à i.e. can’t learn a musical instrument
  
  • Damage to lateral aspect of the spinocerebellum → paravermis = difficulty performing rapid alternating movements. → may observe it in hand movements that are rapidly moving

Question 22

Explain the 2 different types of dysmetria.

Answer 22

• Hypometria (not quite getting to the target which suggest that there is too much inhibition of the UMN)
• Hypermetria (not quite getting to the target which suggest that there is too little inhibition of the UMN, not being able to excite the purkinje fibers enough)

Question 23

What is the concept of an action tremor?

Answer 23

Often accompany the over and undershoot of targeting
If you are trying to correct your error you are going through the cerebellum but it is damaged and will cause action tremor

Question 24

What is ataxia?

Answer 24

• Jerky, imprecise movements
• Think of all the UMN over/under inhibited
  
  • Simultaneously during complex movement
• ***you can think of ataxia as a huge expansion of dysmetria
• ***If we think about a coordinated movement and think about it as being something that needs many UMN outputs in order to coordinate the timing and execution of the variety of muscle pools and muscle fields… any singular UMN can be hypometric or hypermetric; because of that you can have this imbalance that is happening all the time and it is going to result in these outer planes with tiny action tremors occurring every time you try to correct being off task.

Question 25

What are the output structures of the CB? Which targets travel via the superior peduncle? Which travel in the inferior peduncle? Which peduncles “decussate (cross)”?

Answer 25

1. Superior peduncle targets:

• ventral lateral (VL) nucleus of thalamus to the primary motor and premotor cortexes
• superior colliculus

2. Inferior peduncle (mixed) target :
   * vestibular nuclei

The superior peduncle crosses the midline to synapse on the primary motor cortex via the VL complex which controls the motion on the contralateral side (so same side the cerebellar cortex is on which is why the cerebellum is concerned with ipsilateral motion).