Longitudinal divisions of cerebellum Figure 24-1A: The gross longitudinal divisions of the cerebellum are diagrammed on a cartoon of a flattened human cerebellum. The vermis is an anatomically distinct region separated from the hemispheres by sulci (red lines). In contrast, the lateral edge of the paravermis is indistinct (color gradient). Lateral to the paravermis is the lateral hemisphere. Modified from Apps, R., and Hawkes, R. Cerebellar cortical organization: A one-map hypothesis. Nature Rev Neurosci 10: 670–81, 2009, with permission of the publisher, Macmillan publishers, Ltd.

Transverse divisions of cerebellum Figure 24-1B: The gross longitudinal and transverse divisions of the cerebellum are diagrammed on a cartoon of a flattened human cerebellum. The most anterior transverse division of the cerebellum is the anterior zone, which is separated from the rest of the cerebellum by the primary fissure (red line). The most caudal transverse division of the cerebellum is the flocculonodular zone. The hemispheric portion of the flocculonodular zone is separated from the rest of the cerebellum by the posterolateral fissures (blue lines). The vermal portion of the flocculonodular zone includes the nodulus and the uvula (unlabeled). The other two transverse divisions are the central and posterior zones. Modified from Apps, R., and Hawkes, R. Cerebellar cortical organization: A one-map hypothesis. Nature Rev Neurosci 10: 670–81, 2009, with permission of the publisher, Macmillan publishers, Ltd.

Cerebellar cortex layers Figure 24-2A: The cerebellar cortex is intricately organized, as originally described and drawn by Ramón y Cajal. This modified drawing from Cajal shows the basic laminated structure of the cerebellar cortex and illustrates the cell types discussed in the text. Cerebellar cortex has a cell-poor molecular layer, a Purkinje cell layer, and a granule cell layer. The Purkinje cell layer contains the somata of Purkinje cells. One such soma is colored in blue and labeled. An additional Purkinje cell soma is drawn in black. The blue asterisks show the location of more Purkinje cells present at the center of a concentration of climbing fibers. The climbing fibers innervate Purkinje cells so densely that the somata are outlined by the afferent fibers. The Purkinje cell sends an axon into the white matter below, and this axon eventually terminates in the appropriate deep cerebellar nucleus. The apical dendrite of the Purkinje cell branches extensively to form an elaborate dendritic arbor. Drawings are adapted from Sotelo, C. Viewing the brain through the master hand of Ramón y Cajal. Nature Rev Neurosci 4: 71–7, 2003, with permission of the publisher, Macmillan publishers, Ltd.

Climbing and parallel fibers Figure 24-2B: The cerebellar cortex is intricately organized, as originally described and drawn by Ramón y Cajal. This modified drawing from Cajal shows the basic laminated structure of the cerebellar cortex and illustrates the afferent fiber types discussed in the text. A drawing of a transverse section through a folium shows a Purkinje cell (top), climbing fibers, the underlying white matter, and a number of granule cells. One granule cell (gc) is colored red, and its axon, which gives rise to a parallel fiber (pf), is colored in blue. The granule cell axon travels into the molecular cell layer, bifurcates, and then extends for up to millimeters in the medial-lateral direction, in and out of the plane of the paper. Drawings are adapted from Sotelo, C. Viewing the brain through the master hand of Ramón y Cajal. Nature Rev Neurosci 4: 71–7, 2003, with permission of the publisher, Macmillan publishers, Ltd.

Olives, deep nuclei, and lateral lobes Figure 24-3. An unstained section through the cerebellum (top) and a myelin-stained section through the medulla (bottom) illustrate the relationship between the outlines of the lateral cerebellar hemisphere, dentate nucleus (gray matter labeled DN), and inferior olive. The resemblance between the outside contours of these three structures stem from their anatomical relationships. Cells in the main inferior olivary nucleus project topographically to Purkinje cells in the lateral hemisphere, and Purkinje cells in the lateral hemisphere in turn project topographically to the dentate nucleus. Top photograph reprinted with permission from deArmond S., et al. Structure of the human brain: A photographic atlas. New York: Oxford University Press, 1989. Bottom photograph reprinted with permission from Bruni, J.E., and Montemurro, D. Human neuroanatomy: A text, brain atlas, and laboratory dissection guide. New York: Oxford University Press, 2009.

40x more into cerebellum than out Figure 24-4A: The basic inputs and outputs of the cerebellum are diagrammed. There are 40-times more afferent axons into the cerebellum (blue dashed line) than there are efferent axons from the cerebellum.

Simplest circuit through cerebellum Figure 24-4B: The simplest circuit through the cerebellum involves input to deep cerebellar nuclear neurons, which send axons out of the cerebellum to target structures.

Most powerful cerebellar circuit Figure 24-4C: More processing power is contained in the circuit through the cerebellar cortex than the one diagrammed in the previous slide. Afferents to the cerebellum project to the cerebellar cortex. After processing in the cerebellar cortex, involving multiple neurons, Purkinje cells send an axon to the deep cerebellar nuclei. Deep cerebellar nuclear neurons send an axon out of the cerebellum to a target structure in the brainstem or thalamus.

Cerebellar output initiates movement Figure 24-5. Purkinje cells are GABAergic cells that inhibit deep cerebellar nuclear neurons. The firing patterns of three connected cells are diagrammed. Each vertical line represents an action potential. At rest, Purkinje cells fire more rapidly than do either deep cerebellar nuclear neurons or cells in motor control centers. When the discharge rate of the Purkinje cell increases, the deep cerebellar nuclear neuron fires less rapidly,, and when the discharge rate of the Purkinje cell decreases, the deep cerebellar nuclear neuron is disinhibited. Disinhibition results in an increase in the firing rate of the postsynaptic cell, and in turn, in a burst of activity in the motor control center cell. This burst of activity may initiate a movement

Efference copy and reafference Figure 24-6. The sources of efference copy and reafference are shown on a diagram of the basic motor hierarchy. A motor control cell in the cerebral cortex contacts motoneurons and motor interneurons and sends efference copy information to the pontine nuclei. Additional efference copy input derived from the discharge of motoneurons and motor interneurons arises from the ventral horn. Reafference information comes primarily from muscle afferents, Ia and Ib afferents, and cutaneous mechanoreceptors.

Cerebellar cortex circuitry Figure 24-7. Cerebellar circuitry is diagrammed in the coronal plane. In this plane, the dendritic arbor of the Purkinje cells (Pc) is narrow and is represented here as simply a line. A: Purkinje cells receive indirect input from mossy fibers (mf). Many mossy fibers end on each granule cell. Each granule cell sends an axon up into the molecular layer. The granule cell axon bifurcates into a parallel fiber, which extends for long distances in the longitudinal plane of the folia. Along the way, a parallel fiber can contact thousands of Purkinje cells, and each Purkinje cell receives hundreds of thousands of synapses from parallel fibers. The second source of afferent input to the Purkinje cell is the climbing fiber, which arises from the inferior olive. A climbing fiber innervates a few to several Purkinje cells, but each Purkinje cell receives input from only one climbing fiber. B: Recall that Purkinje cells form functional units or microdomains that are oriented as short stripes in the rostral to caudal direction. Here, Purkinje cells belonging to distinct microdomains are denoted by different colors. The parallel fibers arising from granule cells extend across many microdomains and can even cross between different longitudinal zones of the cerebellum.

Spinocerebellar ataxia Figure 24-8. Control subjects and patients with inherited spinocerebellar ataxia were asked to move a joystick on a trajectory that passed through but did not stop in the red square (A) or to move the joystick into the square and stop there (B). The lines indicate the trajectories on four attempts by each subject at this task. Control and patient trajectories were very similar on the “shoot through” task. However, on the pointing task, control subjects’ trajectories all ended within the target square, whereas the patients’ trajectories all overshot (= hypermetria) and then had to come back to the target. Adapted from Tseng, Y., Diedrichsen, J., Krakauer, J.W., Shadmehr, R., and Bastian, A.J. Sensory prediction errors drive cerebellum-dependent adaptation of reaching. J Neurophysiol 98: 54-62, 2007, with permission of the publisher, American Physiological Society.