5. Cerebellum
Part 2 of 4

James Knierim, Ph.D.
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Functional Subdivisions of the Cerebellum

The anatomical subdivisions described above correspond to three major functional subdivisions of the cerebellum.

Vestibulocerebellum.  The vestibulocerebellum comprises the flocculonodular lobe and its connections with the lateral vestibular nuclei.  Phylogenetically, the vestibulocerebellum is the oldest part of the cerebellum.  As its name implies, it is involved in vestibular reflexes (such as the vestibuloocular reflex; see below) and in postural maintenance.

Spinocerebellum.  The spinocerebellum comprises the vermis and the intermediate zones of the cerebellar cortex, as well as the fastigial and interposed nuclei.  As its name implies, it receives major inputs from the spinocerebellar tract.  Its output projects to rubrospinal, vestibulospinal, and reticulospinal tracts.  It is involved in the integration of sensory input with motor commands to produce adaptive motor coordination.

Cerebrocerebellum.  The cerebrocerebellum is the largest functional subdivision of the human cerebellum, comprising the lateral hemispheres and the dentate nuclei.  Its name derives from its extensive connections with the cerebral cortex, via the pontine nuclei (afferents) and the VL thalamus (efferents).  It is involved in the planning and timing of movements.  In addition, the cerebrocerebellum is involved in the cognitive functions of the cerebellum.

Histology and Connectivity of Cerebellar Cortex

The cerebellar cortex is divided into three layers (Figure 5.6).  The innermost layer, the granule cell layer, is made of 5 x 10¹⁰ small, tightly packed granule cells.  The middle layer, the Purkinje cell layer, is only 1-cell thick.  The outer layer, the molecular layer, is made of the axons of granule cells and the dendrites of Purkinje cells, as well as a few other cell types.  The Purkinje cell layer forms the border between the granule and molecular layers.

Figure 5.6

Cerebellar circuitry.  This basic pattern is repeated throughout all regions of the cerebellum.

Granule cells.  Granule cells are very small, densely packed neurons that account for the huge majority of neurons in the cerebellum.  Indeed, cerebellar granule cells account for more than half of the neurons in the entire brain.  These cells receive input from mossy fibers and project to the Purkinje cells.

Other cell types.  In addition to the major cell types (granule cells and Purkinje cells), the cerebellar cortex also contains various interneuron types, including the Golgi cell, the basket cell, and the stellate cell.

Connectivity.  The cerebellar cortex has a relatively simple, stereotyped connectivity pattern that is identical throughout the whole structure.  Figure 6 illustrates a simplified diagram of the connectivity of the cerebellum.  Cerebellar input can be divided into two distinct classes. 

1. Mossy fibers originate in the pontine nuclei, the spinal cord, the brainstem reticular formation, and the vestibular nuclei, and they make excitatory projections onto the cerebellar nuclei and onto granule cells in the cerebellar cortex.  They are called mossy fibers because of the tufted appearance of their synaptic contacts with granule cells.  There is a large degree of divergence in the mossy fiber-granule cell connection, as each mossy fiber innervates hundreds of granule cells.  The granule cells send axons up toward the cortical surface.  Each axon bifurcates in the molecular layer, sending a collateral in opposite directions.  These fibers, called parallel fibers, run parallel to the folds of the cerebellar cortex, where they make excitatory synapses with Purkinje cells along the way (Figure 5.7, rotated view after PLAY).  The two-dimensional arbors of the Purkinje cell dendrites are oriented perpendicular to the parallel fibers.  Thus, the arrangement of Purkinje cells and parallel fibers resembles telephone lines running between telephone poles.  Each parallel fiber makes contact with hundreds of Purkinje cells; because of the high degree of divergence of the mossy fiber-granule cell synapses, the firing of each Purkinje cell can be influenced (disynaptically) by thousands of mossy fibers.
2. Climbing fibers originate exclusively in the inferior olive and make excitatory projections onto the cerebellar nuclei and onto the Purkinje cells of the cerebellar cortex.  They are called climbing fibers because their axons climb and wrap around the dendrites of the Purkinje cell like a climbing vine.  Each Purkinje cell receives a single, extremely powerful input from a single climbing fiber.  In contrast to mossy fibers and parallel fibers, each climbing fiber contacts only 10 Purkinje cells on average, making ~300 synapses with each Purkinje cell.  Thus, the climbing fiber is a restricted, but extremely powerful, excitatory input onto Purkinje cells. 

The Purkinje cell is the sole source of output from the cerebellar cortex.   It is important to note that Purkinje cells make inhibitory connections onto the cerebellar nuclei. (Note the distinction between the Purkinje cells, which constitute the sole output of the cerebellar cortex, and the cerebellar nuclei, which constitute the sole output of the entire cerebellum.)  Almost all of the spikes generated by the Purkinje cell are caused by its parallel-fiber inputs.  These inputs cause the Purkinje cell to fire at a high resting rate (~70 spikes/sec), tonically inhibiting its cerebellar nucleus targets.  The powerful inputs from climbing fibers occur less frequently (~1 spike/sec); thus, they have a minor influence on the overall firing rate of the Purkinje cell.  The Purkinje cell spikes that are generated by climbing fibers are calcium-spikes, however, which allow the climbing fibers to initiate a number of calcium-dependent changes in the Purkinje cell.  As described below, one important change appears to be a long-lasting change in the strength of the parallel-fiber inputs to the Purkinje cell.

Damage to Cerebellum Produces Movement Disorders

Much of what is known about cerebellar function comes from studies of patients with cerebellar damage.  In general, such patients display uncoordinated voluntary movements and problems maintaining balance and posture.  The following are some symptoms of cerebellar damage (we will discuss more symptoms in the next chapter):

1. Decomposition of movement.  Most of our movements involve the coordinated activity of many muscle groups and different joints to produce a smooth trajectory of the body part through space.  Patients with cerebellar dysfunction are unable to produce these coordinated, smooth movements.   Instead, they often break the movements down into their component parts in order to execute the desired trajectory.  For example, touching one’s finger to one’s nose requires the coordinated activity of shoulder, elbow, and wrist joints.  Cerebellar patients must first perform the shoulder movement, then the elbow movement, and finally the wrist movement in sequence, rather than as one, uniform motion. 
2. Intention tremor.  When making a movement to a target, cerebellar patients often produce an involuntary tremor that increases as they approach closer to the target.  For example, if reaching for a cup, the hand starts out in a direct line toward the cup; as it gets closer, however, the hand begins to move back and forth as it attempts to make contact with the cup.
3. Dysdiadochokinesia.  Patients have difficulty performing rapidly alternating movements, such as hitting a surface rapidly and repeatedly with the palm and back of the hand.
   
4. Deficits in motor learning.  Experimental studies have demonstrated that cerebellar damage causes deficits in motor learning in both human patients and experimental animals.  One prominent experimental model is the vestibuloocular reflex (VOR).  This reflex allows us to maintain gaze on an object when the head is rotated (Figure 5.8).  Vestibular signals detect the head movement, and send signals through the cerebellum to the eye muscles to precisely counter the head rotation and maintain a stable center of gaze.  The motor commands to the eyes must be calibrated precisely with experience, and this calibration appears to be the job of the cerebellum.  Experiments have been performed in which subjects wore prisms that magnified the visual image.  When the subjects’ heads were moved, the VOR caused the visual image to shift on the retina rather than remaining stable.  Over days, however, the VOR slowly adjusted, such that the proper compensatory eye movements were made to keep the retinal image stable when the head was rotated.  In experimental animals, lesions to the cerebellum prevent this adjustment of the VOR. 

A second example of cerebellum-dependent motor learning involves the execution of accurate, coordinated movements.  Subjects wore prism goggles that shifted the visual image to the right, and they were asked to then throw balls at a target on the wall.   Because of the prisms, the accuracy of the subjects was initially quite low, as the balls consistently hit to the left of the target.  With repeated practice, however, the subjects became more and more accurate at hitting the target.  When the goggles were removed, the subject now began to throw the balls to the right of the target, because their motor programs had been recalibrated to use the shifted visual input.  Over time, once again, they gradually increased their accuracy.  Patients with cerebellar damage never learned to compensate for the prism, as their balls always landed to the left of the target when the goggles were worn. When the goggles were removed, they were immediately accurate at hitting the target, because they never made compensations for the earlier prism trials.

A third example involves the Pavlovian classical conditioning of the eye blink reflex.  In this task, a neutral stimulus (such as a tone) is paired with a noxious stimulus (such as a puff of air to the eye) that causes a reflexive eye blink.  Over time, experimental animals will learn to close their eye when the tone occurs, in anticipation of the air puff.  This learned eyelid closure is remarkably well-timed to peak at the expected time of the puff.  Animals with cerebellar damage do not learn to produce the eyelid closure in response to the tone.

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