Sites of Plasticity in Eyeblink Conditioning Flashcards
What are the two arguments in sites of plasticity of NMR conditioning?
- Cerebellum vs brainstem
- Cerebellar cortex vs deep cerebellar nuclei
Where does the model predict the plastic synapse is?
Parallel fibre and Purkinje cell synapses
Why does the site of plasticity have to be either the cerebellum or brainstem?
Has to be one or the other given conditioning occurs in decerebrate preparation
(Decerebration = separating the forebrain from the brain stem)
What are the arguments for the brainstem being the site of plasticity?
In agreement that lesions of the anterior interpositus nucleus stops conditioned responses
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
What is the role of the interpositus nucleus in the brainstem pathway?
Interpositus nucleus tonically excites the brainstem pathway
Interpositus nucleus –> excites the red nucleus –> accessory abducens nucleus –> retractor bulbi muscle
Explain the brainstem model
CS + US –> brainstem area X –> CR command –> motor neurons
Interpositus nucleus –> red nucleus –> motor neurons
- Learning in area X produces CR command
- Combines with tonic excitation to produce CRs
What arguments are there against the brainstem being the site of plasticity?
- Evidence for this view is weak - removal of tonic excitation should affect URs but effects on unconditioned response (UR) weak and unreliable - URs still present, even when CRs NOT present
- Evidence against this view is strong - effects of cortical lesions
- Reversible inactivation studies
What is the role of the cerebellar cortex in the brainstem pathway?
Cortex tonically inhibits brainstem pathway
How do cortical lesions effect the brainstem pathway?
Unilateral cortical lesions decrease CR amplitude
Unilateral cortical lesions increase UR amplitude (slightly)
Cannot be explained by simple tonic effect on motor neurons - must be specific effect on CRs
What happens with reversible inactivation of the red nucleus?
Performance affected NOT learning
- No CRs during training with muscimol in red nucleus
- CRs when muscimol wears off
What happens with reversible inactivation of the interpositus nucleus?
Performance AND learning affected
- No CRs during training with muscimol in interpositus nucleus
- No CRs when muscimol wears off - NO LEARNING
What is the conclusion from anti-brainstem arguments?
Conclusion - major site of plasticity for rabbit NMR and eyeblink conditioning is within the cerebellum rather than the brainstem
What evidence is there for the argument of cerebellar cortex vs the deep cerebellar nuclei as the second site of plasticity?
Cortical lesions
Cortical inactivation
Cortical electrophysiology
What have cortical lesions revealed surrounding the role of the cerebellar cortex vs the deep cerebellar nuclei?
Unilateral cortical lesions (in the right place) impair conditioned responses, bilateral lesions abolish them
Necessary evidence but not sufficient
What has cortical inactivation revealed surrounding the role of the cerebellar cortex vs the deep cerebellar nuclei?
Parallel fibre and Purkinje cell synapses use glutamate as a transmitter
Simple spikes generated from activation of AMPA receptors
Can reversibly block these (CNQX)
Can show where drug went in the brain with radioactive labelling
This shows up in the cortex NOT the deep nuclei
No CRs when drug active, no learning of CRs when drug active, no CRs when tested following day (drug has worn off)
What is an issue with CNQX drug as evidence?
CNQX may not be acting just on the synapses between parallel fibres and Purkinje cells
The synapses between mossy fibres and granule cells could also have been affected
However, either of these sites indicates the importance of cerebellar cortex
What has cortical electrophysiology revealed surrounding the role of the cerebellar cortex vs the deep cerebellar nuclei?
Jirenhed et al. (2007) - Found a reduction in firing of Purkinje cells in HVI eyeblink area shown by electrophysiological recording in response to the conditioned response in the last trial compared to the first trial
What issues are there regarding cortical electrophysiology as evidence?
These results were obtained in the decerebrate preparation in ferrets
Preliminary data suggests Purkinje cells behave similarly in intact rabbits and mice
But still some problems with identification of relevant region of cortex
Current evidence supports key role for cerebellar cortex in initial learning
It is possible that the changes in Purkinje cell firing subsequently produce learning in the deep nuclei
Evidence currently very confusing
Why is deep nuclear inactivation also effective at blocking learning?
Interpositus nucleus projects to the inferior olive which completes a loop
Inactivating interpositus nucleus disinhibits the inferior olive which increases complex spikes in the cortex
Fewer simple spikes - in effect, a cortical inactivation
Is the loop a plausible explanation?
Electrophysiological evidence from Zucca et al. (2016) that increasing inferior olive firing rates can abolish simple spikes in cerebellar cortex and suppress conditioned eyeblink responses
But whether inactivating the anterior interpositus nucleus has similar effects has yet to be conclusively demonstrated
