The cerebellum has about 30 million nearly identical functional units, one of which is shown to the left in Figure 1. This functional unit centers on a single, very large Purkinje cell and on a corresponding deep nuclear cell.
Fig1. Deep nuclear cells receive excitatory and inhibitory inputs. The left side of this figure shows the basic neuronal circuit of the cerebellum, with excitatory neurons shown in red and the Purkinje cell (an inhibitory neuron) shown in black. To the right is shown the physical relationship of the deep cerebellar nuclei to the cerebellar cortex with its three layers.
To the top and right in Figure 1, the three major layers of the cerebellar cortex are shown: the molecular layer, Purkinje cell layer, and granule cell layer. Beneath these cortical layers, in the center of the cerebellar mass, are the deep cerebellar nuclei that send output signals to other parts of the nervous system.
Neuronal Circuit of the Functional Unit. Also shown in the left half of Figure 1 is the neuronal circuit of the functional unit, which is repeated with little variation 30 million times in the cerebellum. The output from the functional unit is from a deep nuclear cell. This cell is continually under both excitatory and inhibitory influences. The excitatory influences arise from direct connections with afferent fibers that enter the cerebellum from the brain or the periphery. The inhibitory influence arises entirely from the Purkinje cell in the cortex of the cerebellum.
The afferent inputs to the cerebellum are mainly of two types, one called the climbing fiber type and the other called the mossy fiber type.
The climbing fibers all originate from the inferior olives of the medulla. There is one climbing fiber for about 5 to 10 Purkinje cells. After sending branches to several deep nuclear cells, the climbing fiber continues all the way to the outer layers of the cerebellar cortex, where it makes about 300 synapses with the soma and dendrites of each Purkinje cell. This climbing fiber is distinguished by the fact that a single impulse in it will always cause a single, prolonged (up to 1 second), peculiar type of action potential in each Purkinje cell with which it connects, beginning with a strong spike and followed by a trail of weakening secondary spikes. This action potential is called the complex spike.
The mossy fibers are all the other fibers that enter the cerebellum from multiple sources—the higher brain, brain stem, and spinal cord. These fibers also send collaterals to excite the deep nuclear cells. They then proceed to the granule cell layer of the cortex, where they also synapse with hundreds to thousands of granule cells. In turn, the granule cells send extremely small axons, less than 1 micrometer in diameter, up to the molecular layer on the outer surface of the cerebellar cortex. Here the axons divide into two branches that extend 1 to 2 millimeters in each direction parallel to the folia. Many millions of these parallel nerve fibers exist because there are some 500 to 1000 granule cells for every 1 Purkinje cell. It is into this molecular layer that the dendrites of the Purkinje cells project and 80,000 to 200,000 of the parallel fibers synapse with each Purkinje cell.
The mossy fiber input to the Purkinje cell is quite different from the climbing fiber input because the synaptic connections are weak, so large numbers of mossy fibers must be stimulated simultaneously to excite the Purkinje cell. Furthermore, activation usually takes the form of a much weaker short-duration Purkinje cell action potential called a simple spike, rather than the prolonged complex action potential caused by climbing fiber input.
Purkinje Cells and Deep Nuclear Cells Fire Continuously Under Normal Resting Conditions. One characteristic of both Purkinje cells and deep nuclear cells is that normally both of them fire continuously; the Purkinje cell fires at about 50 to 100 action potentials per second, and the deep nuclear cells fire at much higher rates. Furthermore, the output activity of both these cells can be modulated upward or downward.
Balance Between Excitation and Inhibition at the Deep Cerebellar Nuclei. Referring again to the circuit of Figure 1, note that direct stimulation of the deep nuclear cells by both the climbing and the mossy fibers excites them. By contrast, signals arriving from the Purkinje cells inhibit them. Normally, the balance between these two effects is slightly in favor of excitation so that under quiet conditions, output from the deep nuclear cell remains relatively constant at a moderate level of continuous stimulation.
In execution of a rapid motor movement, the initiating signal from the cerebral motor cortex or brain stem at first greatly increases deep nuclear cell excitation. Then, another few milliseconds later, feedback inhibitory signals from the Purkinje cell circuit arrive. In this way, there is first a rapid excitatory signal sent by the deep nuclear cells into the motor output pathway to enhance the motor movement, followed within another small fraction of a second by an inhibitory signal. This inhibitory signal resembles a “delay line” negative feedback signal of the type that is effective in providing damping. That is, when the motor system is excited, a negative feedback signal occurs after a short delay to stop the muscle movement from overshooting its mark. Otherwise, oscillation of the movement would occur.
Other Inhibitory Cells in the Cerebellum. In addition to the deep nuclear cells, granule cells, and Purkinje cells, two other types of neurons are located in the cerebellum: basket cells and stellate cells, which are inhibitory cells with short axons. Both the basket cells and the stellate cells are located in the molecular layer of the cerebellar cortex, lying among and stimulated by the small parallel fibers. These cells in turn send their axons at right angles across the parallel fibers and cause lateral inhibition of adjacent Purkinje cells, thus sharpening the signal in the same manner that lateral inhibition sharpens contrast of signals in many other neuronal circuits of the nervous system.
