Dean NMR 5

Question 1

What is the first issue with the proposed model?

Answer 1

Cerebellum vs. Brainstem
It has to be one or the other considering conditioning occurs in decerebrate preparation
It is historically a very passionate debate

Question 2

What is the ‘pro-brainstem’ argument?

Answer 2

Both sides agree that lesions of the anterior interpositus nucleus stops conditioned responses but disagree on the mechanism of this effect

• One side claims this is evidence for plasticity in the cerebellum
• The other claims that the lesions work because they affect the brainstem causing a ‘performance deficit’

Deficits not to do with the actual learning but to do with the expression and performance of the learning

Question 3

What do they suggest is the role of the brainstem?

Answer 3

The the IPN tonically excites the brainstem pathways, first of all to the red nucleus which is then relayed to the accessory abducens nucleus
State that learning in brainstem area X produces a CR command and combined with the tonic excitation of motor neurons by the IPN and red nucleus, the CR is produced

Question 4

What is the first of the limitations of the brain stem argument?

Answer 4

1. Evidence in support is weak:
   The removal of tonic excitation should affect UCRs but the effects on UCRs are weak and unreliable. The UCRs are still present even when the CRs are not present

Question 5

What is the second of the limitations of the brainstem argument?

Answer 5

2. Evidence against this view is strong:
   The effects of cortical lesions, the cortex tonically inhibits brainstem pathways so lesions would therefore excite pathways. This should increase CRs but in fact decreases them and in some cases abolishes them.
   Reversible inactivation studies show no CRs during training with muscimol (GABA agonist) in the red nucleus - by doing this there are still UCRs but no CRs. but then the muscimol wears off CRs return to normal

Question 6

What do the findings against the brainstem suggest?

Answer 6

That this pathway is necessary for the performance of the CRs but it is not where the learning takes place

Question 7

What happens when you inject muscimol into the IPN not the red nucleus during training?

Answer 7

There are no CRs during training, but there are also no CRs when the muscimol wears off which indicates that no learning has taken place

Question 8

What conclusions can we make from these findings?

Answer 8

That the major site of plasticity for rabbit NMR conditioning and eye blink conditioning is within the cerebellum

Question 9

What is the second issue with the proposed model?

Answer 9

Cerebellar cortex vs. deep cerebellar nuclei
Arguments about which contains the site of plasticity
Only been settled recently

Question 10

How can we use reversible inactivation of PF-PC transmission instead of cortical lesions?

Answer 10

Want to use this as it is more efficient in investigating effects
Want to reversibly block the transmission at the PF to PC synapse which uses glutamate and binds to AMPA receptors
We can reversibly block AMPA receptors using CNQX and can show where CNQX goes using radioactive labelling
Can only see this in the cerebellar cortex, it does not go into the cerebellar nuclei

Question 11

What did Attwell et al. (2001) find?

Answer 11

That if you give CNQX during sessions of acquisition you don’t see any CRs which you might expect but the day after when the drug wore off there was still no CRs
This is quite strong evidence that basic learning takes place in the cerebellar cortex where the PF-PC synapse is

Question 12

What could be a caution for the findings surrounding CNQX and the cerebellar cortex?

Answer 12

CNQX may not be acting just on the synapses between parallel fibres and purkinje cells
Glutamate is also used at other synapses in the cerebellar cortex such as the synapses between mossy fibres and granule cells so it is possible that these could also have been affected
However, even if this is the case, both of these sites indicate the importance of the cerebellar cortex

Question 13

How is cortical electrophysiology used in the cortex vs. deep nuclei argument?

Answer 13

Jirenhed et al. (2007) recorded from purkinje cells in the HVI eye blink area (cortex)
On the last trial of the CS, the purkinje cells are not firing
Technically difficult to produce hence why it took 25 years

Question 14

What is a caution for Jirenhed et al.’s (2007) study?

Answer 14

The results were obtained in a decerebrate ferret
BUT - Preliminary data suggests Purkinje cells behave similarly in intact rabbits and mice
But there are still some problems with the identification of the relevant region of cortex

Question 15

What is a third caution for the cortex vs. deep nuclei argument?

Answer 15

Current evidence does support a key role for the cerebellar cortex in initial learning and but it is also possible that changes in Purkinje cell firing subsequently produces learning in the deep nuclei
Evidence is currently very confusing

Question 16

What is a question about deep nuclear inactivation?

Answer 16

Why is deep nuclear inactivation effective at blocking learning as well?
The AIPN also projects to the inferior olive and completes a loop (cortex -> DCN -> inferior olive -> cortex)
By inactivating the the AIPN this disinhibits the inferior olive
This increases complex spikes in the cortex, and with fewer simple spikes there is, in effect, cortical inactivation

Question 17

What evidence has been gathered about the IAPN - inferior olive - cortex loop?

Answer 17

Zucca et al. (2016) found that increasing inferior olive firing rates you can:
- abolish simple spikes in the cerebellar cortex
- suppress conditioned eye blink responses
But whether inactivating the AIPN has similar effects has yet to be conclusively demonstrated