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Major anatomical divisions of cerebellum

Anterior lobe

Posterior lobe

Flocculonodular lobe

Vermis: central strip that runs through anterior and posterior lobes


What kinds of information does the cerebellum receive?







In general, what does the cerebellum do?

Rapid, corrective feedback loop, smoothing and coordinating movements


What can lesions of the cerebellum cause?





Intention tremor

Deficits in motor learning



Causes atrophy of the cerebellum


Functional regions of the cerebellum

Cerebrocerebellum (hemispheres): coordination of voluntary movements of limbs, hypothalamic control, cognitive functions?; inputs from cortex via pons; lateral cerebellum influences ipsilateral limbs

Spinocerebellum (intermediate zone, includes vermis): voluntary movements of limbs, postural control and balance; receives fast feedback from spinal cord

Vestibulocerebellum (includes nodulus and flocculus): balance and posture, eye movements; receives vestibular input and input from other brainstem centers via pons


Inputs to the cerebellum

Mossy fibers from pons through middle cerebellar peduncle

Mossy fibers from spinal cord through inferior cerebellar peduncle

Mossy fibers from vestibular nuclei through inferior cerebellar peduncle

Climbing fibers from inferior olive through inferior cerebellar peduncle


Outputs from cerebellar cortex

Carried solely by Purkinje cell axons!

First go straight to deep cerebellar nuclei (dentate nucleus (most lateral), interposed nucleus, fastigial nucleus (most medial))

Deep nuclei project to: thalamus (then to cortex), red nucleus (then to spinal cord via rubrospinal tract), inferior olive (to influence climbing fiber input), vestibular nuclei and reticular formation (influence posture and balance)

Vestibular nuclei


Two inputs to cerebellar cortex

Mossy fibers: carry info about motor context; contact granule cells whose axons are called parallel fibers and contact Purkinje cells; each Purkinje cell receives >80,000 excitatory parallel fiber inputs; input from everywhere except olive

Climbing fibers: carry info indicating errors in movement; directly contact Purkinje cells; each Purkinje cell receives 1 climbing fiber input (but is a really strong input); input info from inferior olive only


Complex spike

Climbing fibers stimulate Purkinje fibers to generate this "special" response

The whole Purkinje neuron "hears" this response/burst of APs

This input from climbing fibers onto Purkinje neurons is a "teacher" that teaches circuit new information


Do Purkinje cells fire spontaneously?

Yes, Purkinje cells fire spontaneously, with no synaptic input

So deep cerebellar nuclei always receiving constant inhibition

Intrinsic activity causes them to fire at ~50 spikes/second

Generated by "pacemaking" types of ion channels


How does Purkinje neuron firing affect movement?

Purkinje neurons are inhibitory, thus when they slow or stop firing their targets are excited (muscles contract!)

Purkinje cells --> deep nuclei (pre-motor neurons) --> thalamus (to motor cortex), vestibular nuclei, inferior olive, red nucleus --> motor neurons --> voluntary movement or reflex

If can get Purkinje fiber to STOP firing, can get/enhance a movement


Conditioned eyeblink reflex

Classic paradigm for studying associative motor learning

Auditory tone at fixed time interval with a puff of air in eye at the end --> then when air puff taken away you still blink your eye

This is because you have reflex memory and anticipate air puff

This learning requires the cerebellum


Associative motor learning

Cerebellar cortex is critically important for forms of associative motor learning

Learning uses experience to keep movements (particularly rapidly alternating sequences of movement) coordinated and well-calibrated for their intended purpose

Mossy fiber to granule cell's parallel fiber inputs to Purkinje cells carry all moment-to-moment sensorimotor info into cerebellar cortex (sensorimotor context)


What do complex spikes indicate?


Rate of complex spikes increases with errors in a novel task

Rate of complex spikes decreases after learning corrects errors in performance

Climbing fibers function as "teachers" providing "error signals"


What do climbing fiber inputs do?

Climbing fiber inputs signal errors in movement and have crucial role in instructing changes during learning

When CF input fires, parallel fiber inputs to Purkinje cells that were active in the time immediately before (100ms) are "punished" by having their synaptic strength reduced

Also, parallel fiber inputs to inhibitory interneurons are increased in strength

Also mossy fibers hypothesized to undergo CF-driven long term increases in strength

These experience-driven changes lead to less excitation of Purkinje cells and increase deep nuclear cell output that will occur in response to particular pattern of mossy fiber activity --> increased muscle contraction in muscles that need to act!


What happens when errors no longer occur?


Climbing fiber firing drops to baseline levels and no plasticity occurs

System maintains well-calibrated reflexes to visual stimuli, vestibular stimuli, reflexive, sequenced movements, learning how to play a sport


Long-term depression

Complex spikes trigger reductions in strengths of coactive parallel fiber inputs to Purkinje cells


How does LTD work at a molecular level?

Coincident climbing fiber and parallel fiber activity causes removal of AMPA receptors on Purkinje cell postsynaptic membrane at only those parallel fiber synapses which were active (LTD)

This mechanism explains the 100ms time window where climbing fibers inhibit parallel fibers that have fired 100ms beforehand, because this process of removing AMPA receptors takes time


1) Climbing fiber inputs (error signals) cause complex spikes in Purkinje cell, which increases Ca2+ throughout the entire Purkinje cell via voltage-gated Ca2+ channels

2) In dendritic spines where parallel fiber inputs come in, DAG/PKC from glutamate binding mGluR (G coupled protein receptor) plus Ca2+ phosphorylate the AMPA receptor to remove it from the synapse

Note: this is how climbing fibers reduce, or "punish" parallel fibers that fired when they weren't supposed to 100ms ago!


Which NT do Purkinje neurons use and how?

Purkinje neurons use GABA and inhibit their targets in the deep nuclei

This "sculpting inhibition" of descending motor commands allows cerebellum to smooth and coordinate movement

Lesions cause ataxia, intention tremor and decomposition of movement


Associative forms of motor learning in the cerebellum

Climbing fiber inputs drive learning:

1) Instruct coactive parallel fiber inputs to Purkinje neurons to undergo long term decreases in strength

2) Instruct coactive parallel fiber inputs to inhibitory interneurons to increase in strength

3) Instruct coactive mossy fiber inputs to deep cerebellar nucleus neurons to increase in strength


How are parallel fiber synapses weakened?

Removal of AMPA glutamate receptors weakens parallel fiber synapses onto Purkinje cells


Regions important for eye movements

Flocculus and nodulus


Regions important for balance, vestibular input, body position



Where do Purkinje neurons synapse before exiting the cerebellum?

Deep cerebellar nuclei


What do mossy fibers and climbing fibers do?

Mossy fibers can bring in excitatory inputs to Purkinje fibers OR inhibitory (mossy --> granule (excitatory) --> inhibitory to Purkinje cell)

Climbing fibers only excitatory inputs to Purkinje fibers

Remember that Purkinje fibers are always inhibitory though, so excitatory TO Purkinje = inhibitory overall


Granule cells

Always excitatory

Axons are called parallel fibers

Mossy fibers --> granule cells --> Purkinje cells

Mossy fibers --> granule cells --> inhibitory interneurons --I Purkinje cells

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