9. Sites of Plasticity: Experimental evidence Flashcards
evidence on sites of plasticity
two issues:
- cerebellum vs brainstem
- cerebellar cortex vs deep nuclei
cerebellum vs brainstem
- has to be one or the other as conditioning occurs in decerebrate portion (no hippocampus or cortex)
- extremely debated topic
brainstem argument
- Llinas and Welsh (1993)
- both sides agree that lesions of the anterior interpositus nucleus stops the CR
- disgaree on the mechanism of this effect
- one side thinks this is evidence for plasticity in the cerebellum whilst others claim that the lesions work because they affect the brainste, (causing a performance deficit)
- lesions of interpositus remove tonic excitation from red nucleus leading to much smaller CR’s (spikes dont meet motoneuron threshold)
anti brainstem argument
- evidence for this view is weak
= removal of tonic excitation should affect UR (eye shut), but effects here are weak and unreliable: UR’s present even when CR’s NOT
= no location proposed for sites of plasticity in brain stem - evidence against this view is strong
= cortical lesions
= reversible inactivation studies
cortical lesions (Gruart et al., 1995) for anti-brainstem argument
- cerebellar cortex tonically inhibits brain stem pathway so interpositus fires more
- red nucleus and accessory abducens nucleus tonically excited by lesions in cerebellar cortex so it should increase the conditioned response (CR)
- unilateral cortical lesions decrease CR amplitude and slightly increase UR amplitude
- cannot be explained by simple tonic effect on motor neurons, must be specific on CR’s
- should increase CR’s but abolishes them
reversible inactivation studies (Krupa et al., 1993)
- no lesions - inject Muskimol into Red nucleus mimicking inhibitory neurotransmitter GABA (lasts 2-5h)
- no CR during this time, all you get is UR
- BUT, when muskimol wears off CR’s are normal
- this pathway necessary for performance of CR’s but its not where learning takes place
- muskimol into anterior interpositus nucleus
- no CR’s during training
- when muskimol wear off no learning has taken place
- no learning takes place from red nucleus or below but could in cerebellar cortex or interpositus
= major site for plasticity in NMR conditioning in rabbits is the cerebellum
cerebellum: nuclei or cortex?
deep cerebellar nuclei prediction comes from anatomy not computational models 3 lines of research: - cortical lesions - cortical inactivation - cortical electrophysiology
cortical lesions (Yeo, 1987) - cerebellar cortex for
- unilateral cortical lesions in the right place impair conditioned responses
- bilateral abolish CR
- cortical lesions can block conditioning, evidence but needs more
cortical inactivation
Attwell et alk., (2001)
- reversibly block transmission at parallel fibre Purkinje cell synapse (uses glutamate as a transmitter)
- post synaptic receptor = AMPA receptors
- you can reversibly block AMPA receotirs with CNQX combined with radioactive labelling
- when you treat cerebellar slices you find that die is confined to cerebellar cortex
- no CR’s when drug is active
- no learning of CR’s when drug active or CR’s next day after drug worn off
CAUTION = CNQX may not be acting just on the specific synapse (PF>PC)
- synapse between mossy fibres and granule cells may also be affects
- both are in the cerebellar cortex though
Cortical electrophysiology
Jirenhead et al (2007)
reduction in firing of PC (in lobule HVI eye blink area) shown by electrophysiology recording
- CS shuts down Purkinje cell firing
CAUTION 2 & 3.
cautions
- CNQX may not be acting just on the specific synapse (PF>PC)
- synapse between mossy fibres and granule cells may also be affects
- both are in the cerebellar cortex though - these data were obtained from decerebrate preparation
- preliminary data finds this is true in rabbits and mice with intact cerebellar cortex - current evidence supports key role for cerebellar cortex in initial learning but it is possible that changes in Purkinje cell firing subsequently produce learning in deep nucleus
- evidence currently confusing (Boele et al., 2013)
Why does deep nuclei inactivation also block learning?
- interpositus nucleus projects to inferior olive completing a loop thats inhibitory
- loop is between cerebellar cortex, cerebellar deep nuclei to drive, back to cortex
- inactivating interpositus disinhibits inferior olive, increasing complex spikes in cortex, decreasing simple spikes (cortical inactivation)
Zucca et al (2016) - can abolish simple spikes in cerebellar cortex which also suppresses conditioned eye blink response
- whether this is the same in the interpositus nucleus is yet to be discovered
