cerebellum (‘little brain’): an intricately corrugated ball of nervous tissue that lies under the rear end of the cerebral hemispheres and is attached to the brain stem by huge bundles of nerve fibres, the cerebellar peduncles, which carry information to and from other parts of the brain.
The cerebellum makes up more than one-tenth of the volume of the human brain. The basic circuitry of nerves within it is essentially similar in all vertebrates and during evolution it has changed much less in size, relative to the body, than have the cerebral hemispheres. These facts suggest that it has some essential, basic function in all vertebrates. Although its exact mechanisms remain unclear, its fundamental role is in the control of
movement. This was clearly recognized by the seventeenth-century physician Thomas Willis in his book
Cerebri Anatome (1664) and the idea can be traced back to the observations and interpretations of Galen (
c.130–210 ad).
The cerebellum comprises an outer, thin layer of
grey matter — the cerebellar cortex — covering a core of
white matter, within which lie three lumps of grey matter on each side of the midline (the deep cerebellar nuclei). Closest to the midline is the
fastigial nucleus and furthest from it is the
dentate nucleus, with the
interpositus nucleus between.
The surface area of the cortex is greatly augmented by folds that run across from side to side — deep ones that divide the surface into ten
lobules, and numerous shallower ones cutting each lobule into
folia. If the cortex were flattened out, it would be a ribbon much longer than it is wide.
The cortex is divided up functionally into longitudinal (i.e. fore-and-aft) strips or zones, each interconnected with a particular deep nucleus. The
vermis, running down the middle, connects with the right and left fastigial nuclei. This is flanked on each side by a
paravermal cortical zone related to nucleus interpositus; and most lateral is the pair of large
cerebellar hemispheres, linked to the dentate nuclei. Since the 1960s studies in animals have shown that each cortical zone comprises many narrower micro-zones, each relating to a particular ‘private’ portion of the corresponding deep nucleus.
The fine structure of the cortex and the circuits that link it with the deep nuclei vary little from place to place, which suggests that all parts of the cerebellum perform a similar basic ‘computation’ or operation. If different parts of the cerebellum have different functional roles, this must be due to differences in their input and output connections rather than their internal wiring.
Damage to part or even all of the human cerebellum, on its own, does not lead to clear impairment of intellect, emotion, or vegetative functions (such as the control of the heart and breathing). But there is abundant evidence that the control of movements is markedly disordered. Typically, patients with cerebellar damage are unsteady on their feet, and their hands shake as they try to point or lift objects (‘intention tremor’); their eyes swing uncontrollably from side to side (
nystagmus); and even their speech can be jerky (‘scanning speech’). These three typical signs, described by the great nineteenth-century French neurologist Charcot, are known as ‘Charcot's Triad’.
The movements most affected vary somewhat depending on the location of the damage. No type of movement is completely lost, but movements ranging in complexity from simple reflex actions to walking, speech, and highly skilled manipulations may all be defective in rate, range, force, and timing. Extremely rarely, individuals are born with little or no cerebellum, and although some of its functions may be taken over by other parts of the brain, movements are permanently clumsy and poorly co-ordinated, suggesting that the learning of motor skills is impaired.
The 600 000 nerve cells in the deep nuclei send messages out of the cerebellum along their fibres (or
axons), which run through the peduncles to a number of nuclei in the brain stem and thalamus. These in turn are connected to the spinal cord and to regions of the cerebral cortex concerned with the control of movement.
Studies of the activity of nerve cells in animals have been the main source of knowledge of how the cerebellum works. Even when movements are not being made, neurons of the deep nuclei are continuously active, producing impulses at rates of 30–50 per second. This continuous background firing arises because the huge number of excitatory nerve fibres that enter the cerebellum, carrying information to the cortex, send side branches into the deep nuclei. In addition, they receive the axons of the 15 million
Purkinje cells, the largest cells in the cortex. These are all inhibitory, using
gamma-amino-butyric acid (GABA) as their transmitter. So, the variation of firing of cells in the deep nuclei, which constitutes the output of the cerebellum and hence modulates movement, is dependent on the relationship between incoming activity and the resulting firing of Purkinje cells.
The incoming nerve fibres, which ultimately control the firing of Purkinje cells, are of two types. The first are the axons of cells in a nucleus in the medulla of the brain stem that glories in the name
inferior olive, and which receives signals, indirectly, from parts of the cerebral cortex concerned with movement. Each of these axons wraps itself around the huge bush of processes (
dendrites) of just one Purkinje cell (hence their name, ‘climbing fibres’), ending in around 2000 synapses. As a result, even a single impulse in a climbing fibre will make its Purkinje cell fire an impulse.
The other class of incoming axons are called ‘mossy fibres’. They are the fibres of several different kinds of nuclei in the brain stem and spinal cord. Some 40 million of them arise from cells in a region of the pons called the
pontine nuclei. Some mossy fibres carry signals from the eyes, inner ears, skin, muscles, and tendons, providing information about the state and
posture of the body. Because movements inevitably generate sensory stimulation, these messages must include ‘feedback’ information regarding current patterns of movement. Other mossy fibres (the majority) carry signals originating in various areas of the cerebral cortex, probably including copies of the current ‘commands-to-move’ emanating from motor areas of the cortex. They inform the cerebellum about movement intentions even before any motion has begun, enabling it to modify movements before errors have started to occur. This essentially ‘predictive’ revision is thought to reduce the extent to which the control of movement depends on feedback from sensory receptors about actual, achieved movement. This is very useful because feedback obviously cannot begin until movement has started, and the delay in a control system causes oscillations and other errors, as engineers well know.
The mossy fibres do not contact Purkinje cells directly: they end mainly on the 50 billion tiny
granule cells in the cortex, whose long
parallel fibres each form synaptic connections on many Purkinje cells. About 95% of the impulses produced by Purkinje cells result from the stream of signals from granule cells.
But how does it all work? Although we know more about the micro-anatomy of the cerebellum than of any other area of the brain, there is still intense debate about exactly what it does. One of the complicating factors is that the strength of each synapse between any parallel fibre and the large number of Purkinje cells that it contacts can be changed, in ways that are invisible even under the microscope. Technically elegant experiments, involving recording from Purkinje cells in slices of cerebellum, maintained alive
in vitro, show that when the cell is activated by its climbing fibre, the synapses of any parallel fibres that are simultaneously active are
decreased in effectiveness, and that this ‘long-term depression’ lasts a very long time. This implies that the climbing fibre can, in effect, ‘teach’ the Purkinje cell to alter its response to any recurrence of the particular pattern of mossy fibre input it was experiencing (representing a particular sensory and motor state of the body) when the climbing fibre was activated. This line of thinking is not universally accepted but has prompted attempts to identify the circumstances (behavioural contexts) in which the climbing fibres increase their activity. At present, the slim available evidence suggests that this occurs when a mismatch develops between the commands-to-move issued to the muscles by the central nervous system and the movements that actually ensue. Climbing fibres may, therefore, function (at least in part) as error-detectors in movement control.
This hypothesis also implies that the cerebellar cortex is the repository of many learned responses or ‘motor memories’ that help to ensure the prompt and accurate execution of skilled movements. Whenever these memories prove to be inadequate, either because a novel movement command is required or because they are fading, control errors will be made and the teaching effect of the climbing fibres will automatically come into play, gradually reducing the errors and improving the skill.
David M. Armstrong
See
nervous system.See also
brain;
cerebral cortex;
memory;
movement, control of.
