Neuro- Cerebellar Learning/disease

Front 1

Functions of Cerebellum

Back 1

1. motor control/coordination
2. motor learning

integrates all PNS info and allows you to execute

Front 2

in the eye-blink conditioning response, how does the cerebellum learn?

Back 2

via Error-Driven Learning

Front 3

what is impt in the conditioned eye-blink reponse

Back 3

1. timing
2. accurate association w/ predictor
3. pair US and CS closely

Front 4

Conditioned Response Reflex Pathway uses what nuclei

Back 4

Interpositus nucleus
It is the site of memory storage

Front 5

Eyeblink Circuit

Back 5

1. tone(CS) activ Vestibular Nuc
2. fed thru Pontine Nuclei
3. Mossy Fibers to Cerebellum

*also throw collaterals to Interpositus Nucleus along w/ entering cerebellum

Front 6

Eyeblink Circuit

Back 6

Pontine fibers synapse on Granular cells
excite granular cells, then excite purkinje cells
Purkinjge cells inhib Interpositus Nuc via GABA

Front 7

eyepuff(US) stimulates the Trigeminal Nucleus

Back 7

excites Climbing Fibers
climb up Purkinje Cells

Front 8

what is the most powerful excitatory input in CNS?

Back 8

Climbing fibers
dont fire very often

Front 9

Granular Cells

important in what?

Back 9

not very robust. takes a lot of them to make PC fire
error dirven information

Front 10

conditioned stimulus pathway uses

Back 10

1. middle cerebellar peduncle
2. Pontine nuclei

for Robust learning

Front 11

Unconditioned Stimulus


reflex pathways require?

Back 11

airpuff
requires Inf Olivary Nucleus

trigeminal nerve. reqd for induction of memory. NOT part of memory storage

Front 12

Interpositus Nucleus

Parallel Fiber synapse on PC

Back 12

is absolutely rqd for memory storage
absolutely rqd for memory storage

Front 13

Parallel fiber synapse is critical for?

Back 13

timing and execution in memory form/storage

Front 14

3 Cerebellar Mechanisms of Memory Storage

Back 14

1. pairing of climbing fibers and parallel fibers activation
2. parallel fibers contribute to contextual info about CS
3. Climbing fibers encode mvmt error information

Front 15

2 possible sites for memory storage

Back 15

1. cerebellar cortex
2. Interpositus nucleus

Front 16

Memory storage in Cerebellar Cortex uses

Back 16

1. Parallel fibers from granular cells synapse on PC- excit
2. CF on PC- excit
3. other interneurons

Front 17

Memory storage in Interpositus Nucleus

Back 17

1. PC on DCN
2. CF on DCN-direct
3. MF on DCN-direct

Front 18

what is the sole output of the cerebellar cortex?

Back 18

Purkinje Cell

fed out as inhib nuclei to DCN

Front 19

excitatory input to Purkinje Cells

Back 19

1. climbing fibers
2. parallel fibers
only synapse on AMPA rec, not NMDA

Front 20

lesions in parallel fibers in rats result in

Back 20

incorrect timing

Front 21

AMPA rec

Back 21

parallel fibers synapse on PC via AMPA

rec is a GPCR and uses PLPC

Front 22

PC response to Parallel fiber stim
to Climbing fiber stim

Back 22

simple spike

complex spike

Front 23

climbing fiber's complex spike on PC allows for what?

Back 23

initiation of a large Calcium current
plays a role in LTD

Front 24

Cerebellar LTD requires

Back 24

inc in postsynaptic calcium

*concurrent activation of parallel and Climbing FIbers gives down-regulation

Front 25

down regulation results in

Back 25

1. internalization of AMPA rec
2. dec output to PC
3. dec inhibition of DCN

Front 26

what causes cerebellar Ataxia?

Back 26

incorrect output from cerebellar cortex to DCN

incoordination
ipsilateral to side of cerebellar lesion

Front 27

cerebellum allows for what type of muscle movements?

Back 27

smooth

talk, breathe, swallow

Front 28

most common causes of acute ataxia?

Back 28

1. viral infections- peds
2. ischemia
3. hemorrhagic stroke

Front 29

most common causes of chronic ataxia?

Back 29

1. alcoholism, dysfxn of PC
2. inherited degen diseases
-SCA
3. Brain metastases
4. Multiple sclerosis

Front 30

damage flocculonodular lobe
medial/vermal region

the more lateral the damage

Back 30

occulomotor disturbances
occulomotor, talking, gait, stance
the more complex the deficits
-intention tremors, dysmetria

Front 31

what processes PNS info to determine required mvmt?

Back 31

Purkinje cells
start to drop out in SCA
-1st sign of pathology

receive info from granular cells (from mossy fibers), from climbing fibers (from ION)

Front 32

Spinocerebellar Ataxias


core problem

Back 32

gropu of inherited genetic diseases w/ variety of phenotypes, progressive
problems w/ gait

lesion in 1 particular gene

Front 33

common SCA problems

SCA7
SCA 6/10
SCA 1/2
SCA 10

Back 33

gaitspeech

hearing loss, blindness
tremors
spasticity
seizures

Front 34

prevalence of SCA

Back 34

all across world, no bias

certain groups have more of certain types of SCA

Front 35

what explains genetic anticipations?

Back 35

dynamic mutation. its changing
inc CAG repeats

normal-10
sick in 70s- 40repeats
sick in 30s- 50repeats

Front 36

where are repeat expansions found in SCA?

Back 36

BOTH coding and noncoding regions

Front 37

SCA-1 encodes for what?

does what?

Back 37

Ataxin-1 protein
RNA-binding domain, mRNA proc

normal ppl have 30-35repeats
GAIN of Fxn Mutation

Front 38

what do CAGs encode?
what happens when they have too many?

Back 38

encode for Glutamine (NOT Glu)
preferential Purkinje cell loss

Front 39

how does SCA-1 kill the Purkinje cells?

Back 39

deposits Ataxin-1 in the nucleus
sequesters essential factors in the nucleus and doesnt allow them to leave

Front 40

what feeds the Purkinje cell?

Back 40

1. parallel fibers (from granular cells)
2. climbing fibers

Front 41

tone(CS) stimulates the vestibular nucleus, this leads to...

Back 41

pontine fibers. these pontine fibers go to cerebellum and are one source of mossy fibers to the Purkinje cells

Front 42

eyepuff(US) stimulates the ION and leads to...

Back 42

ION. this will give off climbing fibers to the purkinje cells in the cerebellum

Front 43

what gives direct excitory(glu) innervation to the deep cerebellar nuclei?

Back 43

1. climbing fibers-collaterals
2. mossy fibers

Front 44

what 3 situations give deep cerebellar nuclei stimulation?

Back 44

1. mossy-direct
2. climbing-direct
3. use of cerebellar cortex

Front 45

parallel fibers have been associated with?

Back 45

correct timing

Front 46

Cerebellar LTD depends on purkinje cells receiving what?

Back 46

1. climbing fiber excit
2. parallel fiber excit

*both at very close proximity

Front 47

Parallel fibers synapse on PC via what type of receptors?

what class of rec are these?

Back 47

thru NMDA receptors


GPCR, use Phospholipase C

Front 48

concurrent activation of parallel and climbing fibers gives you?

Back 48

downregulations. internalization of AMPA receptors

Front 49

what does a dec in AMPA rec result in?

Back 49

1. dec inhibitory response from the purkinje cells to the DCN
2. there is less inhib of DCN
*underlying mechanism of memory

Front 50

repeat expansions in SCA are found in both...

Back 50

coding and noncoding regions

Front 51

induction of cerebellar LTD requires and increases in what?

Back 51

post-synaptic calcium

Front 52

in SCA1 mice polygluatmine expansions (from CAG rpts) causes?

Back 52

preferential purkinje cell loss

Front 53

Parallel fibers contribute to..

Climbing fibers contribute to..

Back 53

contextual information
-what to associate error w/

error information.
-driving the synap learning
-tells you to close your eye when you get airpuff/shock to eye