The cerebellum: the little brain and its amazing connections
8 June 2005
Dr Richard Apps leads the Sensorimotor Control Group in the Department of Physiology. His group uses a range of neuroscience techniques to study brain circuits involved in the control of movement.
We often take for granted every day movements such as reaching with our hand to pick up an object, but without one of the most impressive parts of the brain functioning properly – the cerebellum – we would not be able to do such a task smoothly and accurately.
A remarkable feature of this brain structure is that it contains as many brain cells (neurones) as the rest of the central nervous system put together, yet in humans it is folded into a small space at the back of the head, roughly the size of a clenched fist, where it accounts for just ten per cent of the volume occupied by the brain as a whole. It would seem entirely appropriate then that the word ‘cerebellum’ is derived from the Latin for ‘little brain’.
The astronomical numbers of neurones within the cerebellum (estimated to be 1010) reflects its phenomenal processing power. This is used to integrate a vast array of sensory and other information related to controlling on-going movements and planning future action.
It turns out that most of these brain cells are packed into just one of three distinct layers in the outer shell, or cortex, of the cerebellum – the granular layer, so named because it contains countless tiny granule cells. Immediately above the granular layer is an orderly array of much larger neurones called Purkinje cells. These are the sole output neurones of the cortex and are therefore central to cerebellar contributions to movement control. They send their beautiful fan-shaped processes into the outermost molecular layer, which contains several other cell types and also the processes of granule cells. This highly organized arrangement is quite unlike the apparent chaos seen in some other parts of the nervous system, and is repeated throughout the entire expanse of the cerebellar cortex.
The Group's latest work has shed new light on the way different regions of the cerebellum are connected to the rest of the brain
Different parts of the cerebellum are known to be responsible for controlling different aspects of movement. For example, the middle (vermal) region is concerned mainly with posture and balance, while more lateral (paravermal) parts are involved in the regulation of voluntary limb movements. Given the uniform structure of the cerebellar cortex it follows that differences in function are likely to arise primarily because of differences between cerebellar regions in their interconnections with the rest of the nervous system.
Some of the latest work in the Sensorimotor Control Group has explored this possibility, and shed new light on the way different regions of the cerebellum are connected to the rest of the brain. In particular, a recent collaboration with a research group in Oslo (partly funded by a Benjamin Meaker visiting fellowship award) has studied how the neural projections of two major structures in the brainstem are connected to the cerebellum. These are the inferior olive, which is the sole source of an important and intriguing type of input to the cerebellum called climbing fibres, while the other is the pons, which is the principal source of the other major type of cerebellar input, called mossy fibres.
The pons, in turn, is the principal relay station linking centres of higher brain function in the cerebral cortex with the cerebellum. To appreciate the importance of this pathway a comparison is helpful. In humans, the link between cerebral cortex and pons involves about 40 million fibre connections. By comparison, the optic tract, which relays all visual information from eye to brain, contains just one million fibres. In other words, the cerebro-cerebellar system has a much larger capacity to convey information.
Climbing fibres generate the most powerful electrical impulse known to exist in the mammalian brain
The signals relayed in mossy fibres and climbing fibres can profoundly alter the impulse activity of cerebellar cortical Purkinje cells. Indeed, another remarkable feature of the cerebellar system is the fact that climbing fibres generate the most powerful electrical impulse known to exist in the mammalian brain: a special impulse called a complex spike. The functional significance of these complex spikes remains an enigma but it is clear that they are crucial for normal operation of the cerebellum. If the source of climbing fibres, the inferior olive, is damaged, then movement disorders occur that are similar in many respects to those that arise when the cerebellum itself is affected.
Climbing fibres (so named because they wrap around the processes of individual Purkinje cells like ivy on a tree) also impose a very precise order on cerebellar cortical organization. They preferentially target Purkinje cells oriented in the longitudinal axis, forming a series of discrete bands or zones of cerebellar cortex. Many regard these zones as fundamental to cerebellar information processing, and the way mossy fibres interact with these zones is thought to be key to cerebellar contributions to movement control (for further details see Anatomical and Physiological Foundations of Cerebellar Information Processing by Richard Apps and Martin Garwicz).
In the Bristol-led collaboration, a combination of electrophysiological mapping, neural pathway tracing and computer-assisted 3D reconstruction techniques were used to reveal a new principle of organization for the pathway linking the cerebral cortex with the cerebellum.
The body map in the pons holds true for the projection from corresponding sensory receiving areas of the cerebral cortex
Evidence was obtained that a ‘body map’ exists within the pons whereby brain cells located in small parts of the pons provide mossy fibres to different cerebellar cortical zones. These zones are defined by their receipt of sensory information from specific body parts conveyed by the other source of input to the cerebellum; the climbing fibres.
The study also showed that the body map in the pons holds true for the projection from corresponding sensory receiving areas of the cerebral cortex. For example, a face-receiving area in the primary somatosensory cerebral cortex has connections with brain cells located in the central region of the pons. In turn, brain cells in the same region of the pons connect with a face-receiving area of the cerebellum. This suggests that the cerebellum is ‘wired up’ so that sensory information conveyed directly from the body surface via the climbing fibre system can be compared with similar signals that have undergone higher order processing in the cerebral cortex and then conveyed to the cerebellum by the mossy fibre system.
Overall, the findings provide a new way of looking at how some of the largest pathways in the mammalian brain are functionally linked. This should assist future studies of how the cerebral cortex and the cerebellum work together to control movements (for further details see The NeSys Database on Brain Map Transformations in Cerebellar Systems).