Lecture 16 - Motor Modulation by Cerebellum

I. Cerebellar System - Overview

A. Parts

1. Cerebellar cortex (19.1)

a. Cerebrocerebellum – receives inputs from cerebral cortex; regulates movements requiring skill, including speech

b. Vestibulocerebellum –receives inputs from vestibular nuclei; regulates movements underlying posture and equilibrium

c. Spinocerebellum – receives inputs directly from the spinal cord; lateral part is concerned with gross movements of limbs; proximal part is concerned with movements of proximal muscles and eye movements

2. Deep Cerebellar Nuclei

3. Cerebellar Peduncles

a. Superior peduncle – almost entirely efferent bringing axons from the deep cerebellar nuclei to the red nucleus, deep layers of the superior colliculus and primary motor and premotor areas of the cortex

b. Middle peduncle –afferent, bringing axons from the pontine nuclei

c. Inferior cerebellar peduncle – contains both afferent (from vestibular nuclei, spinal cord and brainstem tegmentum) and efferent fibers (to vestibular nuclei and reticular formation).

B. Features in common with Basal Ganglia

1. Massive cortical inputs

2. Single, main processing station (cerebellar cortex vs. caudate and putamen)

3. Intermediate relay (deep cerebellar nuclei vs. globus pallidus, subthalamic nuclei and substantia nigra)

4. Projections to the thalamus VA/VL complex of thalamus

5. Projections to the premotor or motor cortex

C. Functions of the Cerebellar System

1. Involved in smooth execution and appropriate completion of ongoing movements

2. See Fig. 17.2 from first edition

II. Projections

A. To the cerebellum

1. cerebrocerebellum - receives indirect input from the cerebrum via pontine nuclei (fig 19.3). Pontine nuclei send axons to cerebellar cortex through middle cerebellar peduncle

2. Vestibulocerebellum receives input from vestibular nucleus of medulla

3. Spinocerebellum receives input from the spinal cord. These inputs go into ipsilateral cerebellum via inferior cerebellar peduncle. Somatotopic map of cerebellum (Fig 19.5)

4. Inferior olive puts in modulatory inputs. Involved in learning and memory?

B. From the Cerebellum (fig 19.6)

1. Exit via superior cerebellar peduncle, cross midline to influence appropriate motor cortex (remember that inputs are ipsilateral; therefore outputs must be to contralateral cortex to get back to ipsilateral musculature).

2. Closed loops (19.7) – function?

C. Circuits within the Cerebellum

IV. Mechanism of Motor Modulation by the Cerebellum

A. Central Processing Region (Cerebellar Cortical) Neurons

1. Type - Purkinje cells

2. Morphology - Highly branched dendritic trees, big cell bodies with single axon (look like leafless post oak trees)

3. Inputs from two excitatory fiber systems

a. Mossy fiber inputs - recall that cerbral neurons project to the pontine nuclei which then project to the cerebellar cortex synapses

- axons from pontine nuclei, vestibular system and spinal cord = mossy fibers

- mossy fibers synapse on granule cell neurons which have bifurcating axons referred to as parallel fibers which form excitatory synapses with distal part of Purkinje neuron dendritic spines

b. Olivary inputs - climbing fibers - excitatory in the extreme because of number of synapses made with given Purkinje cell

c. Both fiber systems send excitatory collateral to the deep cerebellar nuclei (see fig 19.8 and 19.9)

4. Significance - integration through summation of information from a variety of inputs.

B. Output - inhibitory signals to deep cerebellar nuclei

1. Overview

a. Purkinje cells form an inhibitory synapse on the DCNs

b. Mossy fibers and climbing fibers form excitatory synapses on the DCNs.

c. Purkinje cells and DCNs are both tonically active (Fig 19.10).

2. Error correction

a. PCs and DCNs recognize errors by comparing patterns of convergent activity concurrently available to both cell types. DCNs generate corrective signals. (Fig 19.6)

b. Recall that both cell types receive excitatory inputs from mossy and climbing fibers, which modulate tonic activity

c. Purkinje cells sample from more mossy fibers than do the corresponding DCNs (but both get the same climbing fiber)

IV. Motor Learning and Memory in the Basal Ganglia and Cerebellum

A. Cerebellar Learning and Memory

1. Blink Reflex Model

a. conditioning of blink reflex

b. Evidence

- lesion of ipsilateral cerebellar cortex and deep cerebellar nuclei abolishes the ability of fully conditioned animals to respond to the conditioned stimulus (from which I infer rabbits blink one eye at a time and only one eye responds to the conditioned stimulus; I guess when your eyes are on opposite sides of your head there’s no reason to blink them in unison)

- Eye cannot be newly conditioned using the eye ipsilateral to the lesion (but contralateral eye still can be conditioned)

- lesions of cerebellar cortex alone prevents conditioning, but doesn’t ablate already conditioned responses (they remember, but they can’t learn; they store info, but can’t encode it)

2. VOR (see fig 18.9 1^st ed)

a. Evidence of learning and memory

b. Evidence of cerebellar involvement - physiological recordings from cerebellar cortex and DCNs

III. Cerebellar lesions Affect Coordinating and terminating Movements

A. Cerebellar Ataxia

1. Symptoms - tremor during movement, instability as limb approaches target, poor estimation of force required to initiate or stop movement, inability to perform smooth, directed movements

2. Deficits reflect ipsilateral representation of information in the cerebellum; also, somatic sensation and vision are represented topographically within the cerebellum.

3. Cerebellum integrates moment-to-moment actions of muscles and joints throughout the body

B. Genetic Analysis of Cerebellar Function

1. Mutant mice with ataxia showed cerebellar pathology

a. Reeler Purkinje cells, granule cells and interneurons are displaced from their usual laminar positions. Paucity of granule cells.

b. Weaver – Most granule cells are lost prior to migrantion from external granule layer during development

2. Cloning of reeler gene revealed that it encoded an ECM protein

3. Cloning of weaver gene revealed that it encoded a Ca²⁺-activated K⁺ channel