Study guidelines
- 1.
Identify the basal ganglia nuclei on brain sections.
- 2.
List the four different basal ganglia circuits (or loops) and describe their function.
- 3.
Summarise the major neurotransmitters involved in the basal ganglia circuits and their function (excitatory or inhibitory): cortical input, globus pallidus, striatum, substantia nigra, subthalamic nucleus, and thalamus.
- 4.
Draw the direct and indirect basal ganglia pathways and predict the outcome of dysfunction of each.
- 5.
Explain the origin of the clinical features of Parkinson disease with respect to its known pathogenesis: tremor, rigidity, bradykinesia, and postural instability.
- 6.
Contrast the clinical features of Huntington chorea, hemiballism, and cerebral palsy with potential sites of basal ganglia dysfunction.
The term basal ganglia is used to designate the areas of the basal forebrain and midbrain known to be involved in the control of movement ( Figure 33.1 ). The basal ganglia comprise the following:
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The striatum (caudate nucleus, putamen, and nucleus accumbens).
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The pallidum (globus pallidus—a part of the lentiform nuclei), which is comprised of an external (lateral) segment and an internal ( medial ) segment . The internal segment has a midbrain extension known as the pars reticulata (or reticular part) of the substantia nigra.
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The subthalamic nucleus (STN).
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The pigmented pars compacta (or compact part) of the substantia nigra.
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The putamen and pallidum together are called the lentiform nucleus.
The vast majority of neurons within the striatum are the γ-amino-butyric acid (GABA)ergic projection neurons (medium spiny projection neurons) that form two functional subgroups expressing different receptors. One subgroup projects to the globus pallidus interna (GPi) and the reticular part of the substantia nigra (SNpr); this constitutes what is called the direct pathway and promotes motor activity (‘go’). The other subgroup projects to the globus pallidus externa (GPe) that projects to the STN; this is the indirect pathway that elicits motor inhibition (‘no go’). There are also giant aspiny cholinergic interneurons , comprising only 1% to 3% of striatum neurons (there are also medium-sized GABAergic interneurons). The interneurons have a direct modulating effect on both subgroups of projection neurons through their presynaptic effects on glutamate release from corticostriatal pathways and dopamine release from nigrostriatal terminals. (The striatum can be subdivided into multiple nuclei that receive their input from different cortical areas or thalamic nuclei and also into functional areas called the matrix and striosome . The striatal neurons of the direct and indirect pathways are within the matrix. Those within the striosome receive their input from the limbic cortex, project to the substantia nigra compacta, and represent the pathway through which the basal ganglia influence the limbic system.)
Basic circuits
It is possible to demonstrate at least four circuits, which commence in the cerebral cortex, traverse the basal ganglia, and return to the cortex:
- 1.
A motor loop , concerned with learned movements
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A cognitive loop , concerned with planning and motor intentions
- 3.
A limbic loop , concerned with emotional aspects of movement
- 4.
An oculomotor loop , concerned with voluntary saccades
Motor loop
The motor loop commences in the sensorimotor cortex and returns there via the striatum, thalamus, and the supplementary motor area (SMA).
Figure 33.2 (derived from Figure 33.1A ) is a schematic wiring diagram, including the posterior part of the striatum, depicting the component parts of the motor loop. Two pathways are known. The direct pathway utilises nuclei in the basal ganglia and thalamus and involves five consecutive sets of neurons ( Figure 33.2A ). The indirect pathway adds the STN to the circuitry and involves seven sets of neurons ( Figure 33.2B ). Separate from these pathways are two projections to the thalamus from the GPi ( ansa lenticularis and lenticular fasciculus ), shown in Figure 33.3 .
All projections from the cerebral cortex arise from pyramidal cells and are excitatory (glutaminergic). So too is the projection from the thalamus to the SMA. Those from the striatum and from both segments of the pallidum arise from medium-sized spiny neurons and are inhibitory. They are GABAergic and also contain neuropeptides of uncertain function.
The nigrostrial pathway projects from the compact part of the substantia nigra to the striatum, where it forms two types of synapses upon those projection neurons ( Figure 33.4 ): those synapsing upon direct pathway neurons are facilitatory, by way of dopaminergic type 1 (D 1 ) receptors on their dendritic spines; and those synapsing upon indirect pathway neurons are inhibitory, by way of dopaminergic type 2 (D 2 ) receptors. Cholinergic interneurons within the striatum are excitatory to projection neurons and are inhibited by dopamine.
A healthy substantia nigra is tonically active, favouring activity in the direct pathway . Facilitation of this pathway is necessary for the SMA to become active before and during movement. SMA activity immediately prior to movement can be detected by means of recording electrodes attached to the scalp. This activity is known as the (electrical) readiness potential , and its manner of production is described in the caption to Figure 33.4 . Impulses pass from the SMA to the motor cortex, where a cerebello-thalamocortical projection selectively enhances pyramidal and corticoreticular neurons within milliseconds prior to discharge.
The putamen and globus pallidus are somatotopically organised, permitting selective facilitation of neurons relevant to (say) arm movements via the direct route, with simultaneous inhibition of unwanted (say) leg movements via the indirect route. For suppression of unwanted movements, the STN, acting upon the particular segment of the body map in the GPi, is especially important, because we know that destruction of the STN results in uncontrollable flailing movements of one or more body parts on the opposite side (see later).
Progressive failure of dopamine production by the pars compacta is the precipitating cause of Parkinson disease (PD) ( Clinical Panel 33.1 ).
PD affects about 1% of people over 65 years of age in all countries. The primary underlying pathology is degeneration of nigrostriatal neurons, resulting in diminished dopamine content within the striatum. [ 18 F]fluorodopa is a mildly radioactive compound which, when injected intravenously, binds with dopamine receptors in the striatum. In symptomatic PD a significant reduction of [ 18 F]fluorodopa binding (and therefore of receptors) is revealed by means of PET scanning ( Figure 33.5 ). (The radiopharmaceutical Ioflupane-I-123 is a cocaine analogue that is taken up by the striatum and can be visualised using single photon emission computed tomography [SPECT] brain imaging; it can assist in the evaluation of adult patients with suspected Parkinsonian syndromes.) One consequence is increased striatal activity, with a shift from the direct to the indirect motor pathway ( Figure 33.6 ).
Nigrostriatal degeneration seems to take the form of a ‘ dying back neuronopathy’ , because dopamine is lost from the striatum earlier than from the midbrain. The spiny striatal neurons also deteriorate, with reduction in the length of
