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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.