1. Jacques Wadiche, PhD Assistant Professor Neurobiology Department wadichej@uab.edu 1/25/08 Cerebellum

2. The cerebellum functions as a rapid, corrective feedback loop, smoothing and coordinating movements. adapted from Purves The motor system is organized as a hierarchy

3. [ somatosensory [ visual [ auditory [ vestibular [ proprioceptive From Control of Body and Mind, (Luther) Gulick Hygiene Series, 1908 What kinds of information does the cerebellum receive?

4. 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

5. Atrophy of cerebellum caused by SCA1 MRI images taken from Harrison’s online (SCA1) and Nolte (normal) SCA1normal

6. adapted from Nolte Anatomical regions of the cerebellum

7. adapted from Purves Cerebrocerebellum – coordination of voluntary movements, cognitive effects? Spinocerebellum & Vestibulocerebellum – posture and balance, eye movements Functional regions of cerebellum

8. adapted from Purves Peduncles and deep nuclei: the inputs and outputs of the cerebellar cortex

9. Cerebral cortex Pons Cerebellum Spinal Cord Inferior Olive Vestibular inputs adapted from Purves Principal inputs to the cerebellum

10. Cerebellar cortex Deep nuclei Red Nucleus Inferior Olive Vestibular Nuclei Thalamus Cerebral Cortex adapted from Purves Principal outputs of the cerebellum

11. adapted from Nolte after Cajal Cellular anatomy

12. Circuits in cerebellum adapted from Nolte

13. How does Purkinje neuron firing affect movement? Purkinje neurons are inhibitory, thus when they slow or stop firing their targets are excited

14. Purkinje cell death is common in genetic forms of ataxia Yang et al. Acta Neuropathologica 100:371 SCA6 = spinocerebellar ataxia type 6 Calbindin-D is a cytoplasmic protein found in Purkinje cells

15. Complex spikes occur in response to climbing fiber excitation Simple spikes are typical action potentials. Purkinje cells show two firing patterns

16. 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 Complex spikes indicate errors

17. Zigmond et al., 1999 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. Classical or Pavlovian conditioning

18. Zigmond et al., 1999 before training during training after training (tone) (air puff) Eyelid movements during a classical conditioning experiment

19. Mauk, 1997 Which pathways carry the information critical for learning?

20. adapted from Purves AMPA receptors are removed at PF synapses LTD of PF synapses

21. 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.