Exam 5: Cerebellum Flashcards
(107 cards)
1
Q
T/F the BG does receives proprioceptive information from muscles?
A
False
- it does not but the cerebellum does
2
Q
what percent of neurons in the brain are in the cerebellum? Types?
A
50%
- Most well known are purkinje cells in the cerebellum
Granule cells are also present
3
Q
how many granule cells are there in the cerebellum?
A
there are 50 billion of them
- even though the cerebellum is small there is a lot of brain density
4
Q
what does the cerebellum do functionally?
A
cerebellum is smoothing out the actual movements happening
- the cerebellum is a machine for feedforward modulation and lets you be on auto pilot for motor plans without the cerebral cortex overthinking
5
Q
why is the cerebellum not wired at birth?
A
because upper and motor neurons are not connected
- The cerebellum is adaptable to whatever body you have and changes as circumstances changes
6
Q
how do we learn movements?
A
The cerebellum is always checking movements for errors and learning new movements with practice
- Generates muscle memory ⇒ to know without knowing
7
Q
how much input vs output does the cerebellum have?
A
There is 40x more input to the cerebellum than its output
- the alpha motor neurons are dumb and they do what they are told to do
8
Q
how many sets of modulator circuits does the cerebellum have?
A
2 sets
- proprioception from muscles and other (like visual)
9
Q
what happens if there are no error signals?
A
the cerebellum does not have much to do in terms of motor control
10
Q
what does rapid excitation facilitate? what role does the cerebellum play in this?
A
movements
- controls the way you want to move compared to how you actually move ⇒ involves a learning circuit
- Takes multiple repetitions engaging the circuit to get movement down
11
Q
how does movement and the cerebellum work and modulate one another? (3)
A
- you choose how you want to move
- the cerebellum modifies things
- you actually move (may not be the identical desired movement)
12
Q
how much brain volume does the cerebellum make up?
A
only 10% but contains 50% of neurons
- Neurons arranged in a regular pattern
- Divided into distinct regions that make connections with different areas of the brain
13
Q
T/F the cerebellum is required for perception or muscle contraction?
A
false
- It indirectly regulates movement by adjusting the output of major descending motor systems of the brain
14
Q
what do lesions in the cerebellum cause? (3)
A
- Disrupt coordination of eye and limb movements
- Impair balance
- Impairs motor learning
15
Q
what type of output do purkinje cells have?
A
inhibitory GABA
- every single purkinje cell is in the same plane and dendrites are in a thin sheet ⇒ unique to cerebellum
16
Q
each purkinje cell receives ____ parallel fiber inputs from ____ cells
A
170,000; granule
- lots and lots of inputs
- many ways into the cerebellum and few ways out
17
Q
parallel fibers
A
axons from granule cells
18
Q
what does chronic abuse of alcohol cause?
A
brain shrinkage overall but cerebellum is especially susceptible
19
Q
cerebellum; what kind of correcting does it do?
A
enables coordination and agility
- We can think of the cerebellum as an autocorrect for learning motor tasks
- coordination, agility, fluency
20
Q
ataxia
A
disorders of voluntary movements ⇒ happens with cerebellar damage
- without the cerebellum, our movement goes all over ⇒ we have to learn how to execute our movements
- poor coordination in movement and thoughts from ataxia
21
Q
what boost is missing in ataxia?
A
Delay in initiating response ⇒ missing the boost from the DCN
22
Q
dysmetria
A
Error in range/coordination of movement
23
Q
Dysdiadochokinesis
A
errors in rate and regulatory of movement
24
Q
how does the cerebellum influence the motor cortex?
A
via the motor thalamus
- not a direct connection to the motor cortex just like the BG
- the entire cerebral cortex is involved with the cerebellum
- descending pathway from brainstem to spinal cord to alpha motor neurons
25
what are the minimum players for coordination of cerebellar function? (4)
- brainstem
- motor thalamus
- primary motor cortex
- medial premotor cortex
26
what is a rudimentary explanation of the cerebellar microcircuit? (3)
1. The premotor cortex proposes a motor plan
2. Your sensory feedback (via muscle spindles, GTOs, and sensory cortex) provides overwhelming options which come in via the 50 billion granule cells available
3. Your cerebellum with repeated trials refines and selects the best pattern of muscle activation to execute the plan smoothly and accurately
27
Effective
not necessarily the strengthening of synapses the cerebellum is doing
- Not LTP
- A small subset of granule cells via their parallel fibers will be effective ⇒ the others don’t die, they will be called upon for other motor learning tasks
28
what are the 3 divisions of the cerebellar cortex?
- cerebrocerebellum
- spinocerebellum
- vestibulocerebellum
29
Cerebrocerebellum
input from the neocortex (lateral regions)
30
Spinocerebellum
receives input form the spinal cord ⇒ has distorted homunculus but not clean like the skin somatosensory
31
2 components of the spinocerebellum?
- intermediate
- vermis
32
intermediate spinocerebellum
inputs from brain system ⇒ spinal cord and trigeminal
33
vermis of spinocerebellum
inputs from auditory and visual systems, some vestibular
34
Vestibulocerebellum
input from the vestibular nuclei
35
what are the other two components of the cerebellum?
axon bundles (peduncles) and deep nuclei sending info out of the cerebellum
36
cerebellar peduncles
large bundles of axons traveling into (afferent) or out of (efferent) the cerebellum ⇒ like cranial nerves in head
- Peduncles don’t have cell bodies just axon tracts
- 3 peduncles on each side of the cerebellum
37
what do the cerebellar peduncles anatomically connect?
Connect the cerebellum to the rest of the brain
38
what are the 3 cerebellar peduncles?
- superior
- middle
- inferior
39
superior cerebellar peduncle
mostly efferent axons from cerebellum to motor thalamus like BG
40
middle cerebellar peduncle
afferent axons from cortex to cerebellum ⇒ huge
- From the entire neocortex
41
inferior cerebellar peduncle
mixture of afferent and efferent to the spinal cord
42
Deep cerebellar nuclei (DCN)
output of the cerebellum (3 of them)
- Dentate nucleus
- Interposed nucleus (2)
- Fastigial nucleus
43
what NT input do the deep cerebellar nuclei receive? from what? (2)
- excitatory glutamate signals directly from mossy fibers and climbing fibers
- receive inhibitory GABA signals from purkinje neurons in the cerebellar cortex ⇒ The neurons are like a clamp holding down the cerebellum from sending outputs
44
where do axons of the DCN project out of the cerebellum?
along the superior or inferior cerebellar peduncle
45
what are the 2 parallel pathways (names) going into the cerebellum to do motor learning?
1. motor planning pathway
2. proprioceptive and vestibular info
46
motor planning pathway
1. frontal/parietal cortex
2. goes to red nucleus (minor) and pontine nucleus (major)
- red nucleus goes to inferior olive which goes to cerebellar cortex/deep cerebellar nuclei through the inferior cerebellar peduncle
- pontine nuclei goes through the middle cerebellar peduncle to the cerebellar cortex/deep nuclei => this and the spinal cord give input from all of the sensory areas
47
what type of fiber does the pontine nuclei pathway use at the middle cerebellar peduncle?
mossy fiber
48
what type of fiber does the red nucleus/inferior olive pathway use at the inferior cerebellar peduncle?
climbing fiber
49
is the motor planning pathway contralateral or ipsilateral?
contralateral
50
proprioceptive and vestibular info pathway
1. input from the spinal cord and vestibular nuclei
2. into inferior cerebellar peduncle
3. goes to cerebellar cortex/deep nuclei
51
what type of fiber does the proprioceptive and vestibular path use?
mossy fiber
52
Is the proprioceptive and vestibular path ipsilateral or contralateral?
ipsilateral
53
Climbing fibers
tells you what you want to do ⇒ the cerebellum figured out what is the most relevant complement of muscles
54
what is the comparison between the two pathways involved in the cerebellum?
Comparison happens between mossy fibers from neocortex (sensory cortex) and climbing fibers from sensory afferent from proprioceptive and vestibular info
- Depending on what the motor task is
55
mossy fibers
- from the spinal cord ⇒ muscle spindle and GTO sensory info
- From the sensory neocortex ⇒ via the pontine
56
what do mossy fibers vs. climbing fibers go to?
mossy to granule; climbing to purkinje
57
how are training error signals done?
via the motor cortex ⇒ red nucleus ⇒ olive ⇒ climbing fiber
58
what are the proprioceptive types? (3) fnxs?
- Muscle spindle (Ia, II) ⇒ stretch
- Golgi tendon organ (Ib) ⇒ contraction
- Joint receptors ⇒ limb position/movement
59
which tracts ascend to the cerebellum via the spinocerebellar tract? (3)
- Cuneocerebellar tract
- posterior/dorsal spinocerebellar tract
- anterior/ventral spinocerebellar tract
60
what are the two output sets (names + structures) from the cerebellum to motor systems?
- Cortical motor system => motor thalamus and superior cerebellar peduncle
- Brainstem => inferior peduncle (Inferior has a separate circuit from the other two)
61
what happens with damage to the cerebrocerebellum or DCN on one side of the cerebellum?
because the motor cortex controls the contralateral side of the body, damage will primarily affect motor planning (movements) on the ipsilateral side to the damage
62
how does cerebellar output through the cortical system work? (Pathway)
1. Cerebellar cortex
2. Deep cerebellar nuclei (dentate and interposed)
3. cross contralateral via the superior cerebellar peduncle
4. Motor thalamus (VL)
5. Primary motor cortex and premotor cortex
- also goes to inferior olive from the deep cerebellar nuclei
63
how does the output pathway from the cerebellum via the brainstem work?
1. cerebellar cortex
2. deep cerebellar nuclei (fastigial)
3. reticular formation
4. through the anterior medial white matter (spinal cord) ipsilaterally
5. LMN in medial ventral horn which are alpha and gamma motor neurons
64
what happens with damage to the cerebellum via brainstem nuclei in the inferior peduncle pathway? Which parts of the cerebellum?
because the reticular formation (also superior colliculus and vestibular nuclei) has many bilateral projections, damage to the spinocerebellum (intermediate and vermis) and the vestibulocerebellum may affect the body bilaterally or may have little effect if the other side of the cerebellum is intact
65
how many layers are in the cerebellum? what are they?
3 layers
1. molecular
2. purkinje
3. granular
66
what does the reticular formation innervate?
alpha motor neurons
- gamma motor neurons are also important
67
what cell is the output of the cerebellar cortex?
purkinje cell
68
what is the output of the cerebellum?
DCN neurons
69
where do mossy fibers come from?
pontine, vestibular, and spinal cord
70
where do climbing fibers come from?
inferior olive
71
what cell types are in the molecular layer?
- purkinje cell dendrites but not the cell body
- climbing fiber axons on the purkinje dendrites
- granule cell axons
- stellate cell (extra)
- basket cell (extra)
- Golgi cell axon
72
what cell types are in the purkinje layer?
- purkinje cell bodies
- climbing fiber and granule cell passing through
- basket cell axon
- golgi cell axon
73
what cell types are in the granule layer?
- purkinje cell axon (and climbing fiber)
- granule cell body and dendrites
- mossy fiber
- Golgi cell body and dendrites
74
how many climbing fibers for each purkinje cell?
1:1 relationship
- for each of the 15 million purkinje cells ⇒ substrate for ultra precise motor learning
75
how many parallel fibers to the purkinje cell?
170,000 from the granule cell
- lots of sensory input
76
what does activating the climbing fiber do?
generates a calcium burst spike where calcium comes into the purkinje cell ⇒ plasticity learning signal
- This is the learning signal and substrate of the cerebellum
- Calcium spike is important in plasticity but is not the same bursting as thalamic relays ⇒ big calcium influx but different ion channels
- Without that there is no motor learning
77
what are interneurons responsible for in the cerebellum?
gain of the system, preventing runaway excitation, preventing epilepsy ⇒ not for motor learning and most important functions of cerebellum
78
what are the relevant cells in the circuit for motor learning? (4)
- Purkinje
- Climbing fibers
- DCN
- Granule cells
79
T/F you can move without the cerebellum?
True
- don't expect to motor learn to drive a car, become a neurosurgeon, or play competitive sports
- Refinement of moving would be the problem
80
what is the deep excitatory loop?
the mossy fiber synapses releasing glutamate on the granule cell and the DCN while the climbing fiber synapses on the DCN releasing glutamate and the purkinje cell dendrites
81
what is the cerebellar cortical loop
1. the mossy fiber synapses on the granule cell releasing glutamate
2. the granule cell and its parallel fibers synapses on the purkinje cell releasing glutamate
3. the purkinje cell releases GABA on the DCN inhibiting it
4. the DCN cannot release glutamate on the thalamus which goes to the primary motor cortex and is not activated
82
what happens to the cerebellar loop with motor learning? (Molecular pathway)
1. the parallel fibers and climbing fiber activate together and there are calcium spike bursts from purkinje cells and the mossy fiber and granule pathway are also weakened
2. the granule cell and its parallel fibers synapses on the purkinje cell but starts releasing less glutamate causing LTD
3. the purkinje cell releases less GABA on the DCN releasing it
4. the DCN releases glutamate on the thalamus which goes to the primary motor cortex
5. this acts on the best muscles
83
what is required for LTD in the purkinje neuron? (2)
Simultaneous activation by parallel fiber (PF) and climbing fiber (CF)
- causes a subsequent decrease in the EPSP from the parallel fiber synapse onto the purkinje cell = LTD
- you can impale the dendrites of the purkinje to record its EPSPs while you stimulate the granule cell and the climbing fiber simultaneously
84
if you don't have plasticity what can't you haven the cerebellum? what enables this?
motor learning; inhibition of purkinje cells allows the DCN neuron to fire more
85
what synapse in the cerebellar cortical loop has the LTD?
LTD happens at the parallel fiber to purkinje cell synapse by pairing electrical stimulation of the climbing fiber and the parallel fiber
86
where can LTD be measured in the cerebellar cortical loop?
measuring the LTD in the purkinje cell
87
what is the main goal of the cerebellar cortical loop?
Trying to weaken a subset of the sensory input ⇒ this unleashes the DCN to do its thing
88
when are climbing fibers heavily recruited?
during motor movement for motor learning
- spike burst in purkinje cell evoked LTD of parallel fibers
- With each iteration, LTD gradually wipes away the long inhibitory loop to the desired muscles ⇒ the indirect part is much more powerful than the short direct part
89
what does the purkinje cell control? what happens with motor learning establishment?
whether the DCN can fire or not --Pre-training its clamped down as much as possible; learning eliminates the whole pathway prior to the DCN
- If you weaken that pathway, the DCN can do its thing on the best muscle
90
which synapses in the cerebellar cortical loop are inhibitory?
the only inhibitory synapse is the purkinje cell releasing GABA on the DCN and all other synapses release glutamate
91
T/F cerebellar disease is mostly genetic? What possible genes?
True
- genetic defect (ataxin 1 gene) needed for the synthesis of the ataxin 1 protein
92
what causes spinocerebellar ataxia (SCA1)? What makes it progressive?
mutation of the ataxia gene
- deterioration of bulbar function
93
what does chronic alcoholism do to the cerebellum?
dramatically shrinks the size of cerebellum/kills neurons
- metabolic fragility in the cerebellum at the purkinje cells which are very susceptible to cell death with metabolic differences from alcohol use at high amounts
94
Dysarthria
impaired movement of muscles used for speech
95
what does deterioration of bulbar function do?
Cognitive impairment
- the brain stem controls breathing
96
are other regions of the cerebellar cortex as susceptible as the spinocerebellum?
No, the other regions of the cerebellar cortex are less susceptible to lesions or genetic mutations than the spinocerebellar part
97
what is the onset and timeline for people with SCA1
age of onset usually in the 40s ⇒ death within 10-15 years
98
what in the genome causes SCA1?
caused by CAG repeats (poly glutamine) in the ataxin 1 protein (ATXN1)
- autosomal dominant
99
what amounts of repeats causes SCA1?
- 6-38 repeats has no disease
- 39-40 has possible disease but increased status
- 41-49 is affected
100
what repeats put offspring at risk for SCA1?
- none for under 39
- 39-40 has <50% risk
- 41-49 has 50%
101
where is ataxia 1 protein expressed? what does increased CAG repeats lead to?
throughout the body
- increased number of CAG repeats leads to protein aggregation
102
how does phosphorylation affect ataxin 1; what are ataxin typical fnxs?
incorrect phosphorylation can cause disease in a mouse with a normal number of repeats
- normal molecular functions may include RNA binding and regulation in spliceosome
103
in the ____ and ____, ataxin1 may be involved in _________
SVZ; hippocampus; adult neurogenesis
104
what may be the cause of cognitive impairment?
Aggregation of protein occurs and immune system tries to come in and rescue but that creates more problems
105
hypotonia
decreased resistance to passive limb movement
106
is degeneration or being born without a cerebellum worse?
having degeneration as an adult is way worse than being born without a cerebellum
- You can never be as good in learning motor tasks if you are born without a cerebellum but the symptoms are less severe compared to those who have developmental neurodegeneration of the cerebellum
- The neocortex will try and compensate to improve motor performance
107
Motor learning
Wiping out the cerebellar cortical loop associated with the best muscles for a given motor task
