BASAL GANGLIA AND CEREBELLUM
A. The basal ganglia:
What are the basal ganglia? The name is confusing, as generally a ganglion is a collection of cell bodies outside the central nervous system. Blame the early anatomists. The basal ganglia are a collection of nuclei deep to the white matter of cerebral cortex. The name includes: caudate, putamen, nucleus accumbens, globus pallidus, substantia nigra, subthalamic nucleus, and historically the claustrum and the amygdala. However, the claustrum and the amygdala do not really deal with movement, nor are they interconnected with the rest of the basal ganglia, so they have been dropped from this section. Other groupings you may hear are the striatum (caudate + putamen + nucleus accumbens), the corpus striatum (striatum + globus pallidus), or the lenticular nucleus (putamen + globus pallidus), but these groupings obviously get confusing very quickly, so we will try to avoid them.
The anatomy of these structures should be a review from the “coronal and horizontal sections” lab. Here once again are the basal ganglia as they appear when stained for myelin:
An alternate stain is the acetylcholinesterase (AChE) stain. This technique stains for the enzyme that degrades acetylcholine (ACh), a major neurotransmitter. Areas which use ACh generally stain darkly. Here is a section through monkey brain, stained for AChE.
You can see that the caudate and putamen are stained, while the globus pallidus remains fairly pale. This emphasizes their different functions and connections. And those are…?
B. Different functions and connections:
The relationships between the nuclei of the basal ganglia are by no means completely understood. When dealing with the brain, you may sometimes be tempted to think that everything is connected to everything else. Take heart, some fairly simple generalizations and schematics can be drawn.
The caudate and putamen receive most of the input from cerebral cortex; in this sense they are the doorway into the basal ganglia. There are some regional differences: for example, medial caudate and nucleus accumbens receive their input from frontal cortex and limbic areas, and are implicated more in thinking and schizophrenia than in moving and motion disorders. The caudate and putamen are reciprocally interconnected with the substantia nigra, but send most of their output to the globus pallidus (see diagram below).
The substantia nigra can be divided into two parts: the substantia nigra pars compacta (SNpc) and the substantia nigra pars reticulata (SNpr). The SNpc receives input from the caudate and putamen, and sends information right back. The SNpr also receives input from the caudate and putamen, but sends it outside the basal ganglia to control head and eye movements. The SNpc is the more famous of the two, as it produces dopamine, which is critical for normal movement. The SNpc degenerates in Parkinson’s disease, but the condition can be treated by giving oral dopamine precursors.
The globus pallidus can also be divided into two parts: the globus pallidus externa (GPe) and the globus pallidus interna (GPi). Both receive input from the caudate and putamen, and both are in communication with the subthalamic nucleus. It is the GPi, however, that sends the major inhibitory output from the basal ganglia back to thalamus. The GPi also sends a few projections to an area of midbrain (the PPPA), presumably to assist in postural control.
This schematic summarizes the connections of the basal ganglia as described above.
Although there are many different neurotransmitters used within the basal ganglia (principally ACh, GABA, and dopamine), the overall effect on thalamus is inhibitory. The function of the basal ganglia is often described in terms of a “brake hypothesis”. To sit still, you must put the brakes on all movements except those reflexes that maintain an upright posture. To move, you must apply a brake to some postural reflexes, and release the brake on voluntary movement. In such a complicated system, it is apparent that small disturbances can throw the whole system out of whack, often in unpredictable ways. The deficits tend to fall into one of two categories: the presence of extraneous unwanted movements or an absence or difficulty with intended movements.
C. Lesions of the basal ganglia:
Lesions in specific nuclei tend to produce characteristic deficits. One well-known disorder is Parkinson’s disease, which is the slow and steady loss of dopaminergic neurons in SNpc. An instant Parkinson-like syndrome will result if these neurons are damaged. This happened several years ago to an unfortunate group of people who took some home-brewed Demerol in search of a high. It was contaminated by a very nasty byproduct, MPTP ,which selectively zapped the SNpc neurons. The three symptoms usually associated with Parkinson’s are tremor, rigidity, and bradykinesia. The tremor is most apparent at rest. Rigidity is a result of simultaneous contraction of flexors and extensors, which tends to lock up the limbs. Bradykinesia, or “slow movement”, is a difficulty initiating voluntary movement, as though the brake cannot be released.
Huntington’s disease, or chorea, is a hereditary disease of unwanted movements. It results from degeneration of the caudate and putamen, and produces continuous dance-like movements of the face and limbs. A related disorder is hemiballismus, flailing movements of one arm and leg, which is caused by damage (i.e., stroke) of the subthalamic nucleus.
D. The cerebellum:
The cerebellum is involved in the coordination of movement. A simple way to look at its purpose is that it compares what you thought you were going to do (according to motor cortex) with what is actually happening down in the limbs (according to proprioceptive feedback), and corrects the movement if there is a problem. The cerebellum is also partly responsible for motor learning, such as riding a bicycle. Unlike the cerebrum, which works entirely on a contralateral basis, the cerebellum works ipsilaterally.
The cerebellum (“little brain”) has convolutions similar to those of cerebral cortex, only the folds are much smaller. Like the cerebrum, the cerebellum has an outer cortex, an inner white matter, and deep nuclei below the white matter.
Cat cerebellum, sagittal section
Single folium, enlarged
If we enlarge a single fold of cerebellum, or a folium, we can begin to see the organization of cell types. The outermost layer of the cortex is called the molecular layer, and is nearly cell-free. Instead it is occupied mostly by axons and dendrites. The layer below that is a monolayer of large cells called Purkinje cells, central players in the circuitry of the cerebellum. Below the Purkinje cells is a dense layer of tiny neurons called granule cells. Finally, in the center of each folium is the white matter, all of the axons traveling into and out of the folia.
These cell types are hooked together in stereotypical ways throughout the cerebellum.
Mossy fibers are one of two main sources of input to the cerebellar cortex. A mossy fiber is an axon terminal that ends in a large, bulbous swelling. These mossy fibers enter the granule cell layer and synapse on the dendrites of granule cells (right); in fact the granule cells reach out with little “claws” to grasp the terminals. The granule cells then send their axons up to the molecular layer, where they end in a T and run parallel to the surface. For this reason these axons are called parallel fibers. The parallel fibers synapse on the huge dendritic arrays of the Purkinje cells.
However, the individual parallel fibers are not a strong drive to the Purkinje cells. The Purkinje cell dendrites fan out within a plane, like the splayed fingers of one hand. If you were to turn a Purkinje cell to the side, it would have almost no width at all. The parallel fibers run perpendicular to the Purkinje cells, so that they only make contact once as they pass through the dendrites.
Although each parallel fiber touches each Purkinje cell only once, the thousands of parallel fibers working together can drive the Purkinje cells to fire like mad.
The second main type of input to the folium is the climbing fiber. The climbing fibers go straight to the Purkinje cell layer and snake up the Purkinje dendrites, like ivy climbing a trellis. Each climbing fiber associates with only one Purkinje cell, but when the climbing fiber fires, it provokes a large response in the Purkinje cell.
The Purkinje cell (left) compares and processes the varying inputs it gets, and finally sends its own axons out through the white matter and down to the deep nuclei. Although the inhibitory Purkinje cells are the main output of the cerebellar cortex, the output from the cerebellum as a whole comes from the deep nuclei. The three deep nuclei are responsible for sending excitatory output back to the thalamus, as well as to postural and vestibular centers.
There are a few other cell types in cerebellar cortex, which can all be lumped into the category of inhibitory interneuron. The Golgi cell is found among the granule cells. The stellate and basket cells live in the molecular layer. The basket cell (right) drops axon branches down into the Purkinje cell layer where the branches wrap around the cell bodies like baskets.
E. Inputs and outputs of the cerebellum:
The cerebellum operates in 3’s: there are 3 highways leading in and out of the cerebellum, there are 3 main inputs, and there are 3 main outputs from 3 deep nuclei. They are:
The 3 highways are the peduncles, or “stalks”. There are 3 pairs: the inferior, middle, and superior peduncles.
The 3 inputs are: Mossy fibers from the spinocerebellar pathways, climbing fibers from the inferior olive, and more mossy fibers from the pons, which are carrying information from cerebral cortex. The mossy fibers from the spinal cord have come up ipsilaterally, so they do not need to cross. The fibers coming down from cerebral cortex, however, DO need to cross (remember the cerebrum is concerned with the opposite side of the body, unlike the cerebellum). These fibers synapse in the pons (hence the huge block of fibers in the cerebral peduncles labeled “corticopontine”), cross, and enter the cerebellum as mossy fibers.
The 3 deep nuclei are the fastigial, interposed, and dentate nuclei. The fastigial nucleus is primarily concerned with balance, and sends information mainly to vestibular and reticular nuclei. The dentate and interposed nuclei are concerned more with voluntary movement, and send axons mainly to thalamus and the red nucleus.