Download Cerebellum

1/25/08
Cerebellum
Jacques Wadiche, PhD
Assistant Professor
Neurobiology Department
[email protected]
The motor system is organized as a
hierarchy
The cerebellum
functions as a
rapid, corrective
feedback loop,
smoothing and
coordinating
movements.
adapted from Purves
What kinds of information does the
cerebellum receive?
 somatosensory
 visual
 auditory
 vestibular
 proprioceptive
From Control of Body and Mind,
(Luther) Gulick Hygiene Series, 1908
Cerebellum: a fast feedback loop for
coordinating movement
Cerebellar lesions cause:
nystagmus
ataxia
dysdiadochokinesia
dysmetria
intention tremor
also, deficits in
motor learning
Purves, 18-7
Atrophy of cerebellum caused by SCA1
SCA1
normal
MRI images taken from Harrison’s online (SCA1) and Nolte (normal)
Anatomical regions
of the cerebellum
adapted from Nolte
Functional regions
of cerebellum
Cerebrocerebellum –
coordination of
voluntary movements,
cognitive effects?
Spinocerebellum &
Vestibulocerebellum –
posture and balance,
eye movements
adapted from Purves
Peduncles and deep nuclei: the inputs
and outputs of the cerebellar cortex
adapted from Purves
Principal inputs to
the cerebellum
Cerebral cortex
Pons
Cerebellum
Vestibular Inferior
inputs
Olive
Spinal
Cord
adapted from Purves
Principal outputs of
the cerebellum
Cerebellar cortex
Deep nuclei
Thalamus
Vestibular Inferior
Red
Nuclei
Olive Nucleus
Cerebral
Cortex
adapted from Purves
Cellular anatomy
adapted from Nolte
after Cajal
Circuits in cerebellum
adapted from Nolte
How does Purkinje neuron firing affect
movement?
Purkinje neurons are inhibitory, thus when they slow or stop firing their
targets are excited
Purkinje cell death is common in genetic
forms of ataxia
SCA6 = spinocerebellar ataxia type 6
Calbindin-D is a cytoplasmic protein found in
Purkinje cells
Yang et al. Acta Neuropathologica 100:371
Purkinje cells show two firing patterns
• Complex spikes occur in response to climbing fiber excitation
• Simple spikes are typical action potentials.
Complex spikes indicate errors
Rate of simple spikes
~ 50 / s
Rate of complex spikes
~ 1-2 / s
Rate of complex spikes
increases with errors in a
novel task.
Rate of complex spikes
decreases after learning
corrects errors in
performance.
Zigmond et al., 1999
Climbing fibers thus function as “teachers” and
adaptively shape cerebellar output
Classical or Pavlovian conditioning
Learning causes a
conditioned stimulus
or CS to be linked to
an unconditioned
stimulus or US.
This allows the CS
to elicit the
response (R) when
delivered by itself.
Zigmond et al., 1999
Eyelid movements
during a classical
conditioning
experiment
before
(tone)
(air puff)
training
during
training
after
training
Zigmond et al., 1999
Which pathways carry the
information critical for learning?
Mauk, 1997
LTD of PF synapses
AMPA
receptors are
removed at
PF synapses
adapted from
Purves
Summary
1. Purkinje neurons inhibit their targets in the deep nuclei.
This “sculpting inhibition” of descending motor commands
allows cerebellum to smooth & coordinate movement.
Lesions cause ataxia, intention tremor & decomposition of
movement.
2. Inputs to cerebellum: mossy fibers (pons & spinal cord) &
climbing fibers (inferior olive). Outputs from cerebellum:
Purkinje cell axons (to red nucleus, thalamus, inferior olive,
and vestibular nuclei) through DCN.
3. Associative forms of motor learning occur in the
cerebellum. Climbing fiber inputs instruct co-active parallel
fiber inputs to undergo long term decreases in strength.
4. At a cellular level, parallel fiber synapses are weakened by
removal of AMPA-type glutamate receptors.