Topography of the basal ganglia and adjacent structures
To understand the pathogenesis of Parkinson's disease, it is necessary to clearly visualize the spatial arrangement of the structures of the extrapyramidal system. They are closely connected with the diencephalon and the ventricular system.
- Caudate nucleus (nucleus caudatus): C-shaped. The massive head is adjacent to the anterior horn of the lateral ventricle, while the attenuated tail curves posteriorly around the thalamus, extending into the temporal lobe (where the amygdala lies at its end).
- Putamen (putamen): A massive nucleus lateral to the thalamus. During embryogenesis, fibers of the internal capsule grow through the basal ganglia, dividing them. However, the putamen maintains a connection with the head of the caudate nucleus via cellular bridges of gray matter, forming the corpus striatum (striatum).
- Globus pallidus (globus pallidus): Located medially to the putamen and separated from it by the medial medullary lamina of white matter. Together, they form the lentiform nucleus. The pallidus is the phylogenetically older nucleus (paleostriatum).
- Substantia nigra (substantia nigra): An associated nucleus of the midbrain. Posteriorly, the globus pallidus directly borders its rostral (red) zone. The specific dark color of the substantia nigra is due to a high concentration of melanin.
Afferent and efferent connections of the striatum
The corpus striatum (corpus striatum) collects the main volume of information from various parts of the brain.
Main afferent pathways to the striatum:
- From the cerebral cortex: Descending pathways from pyramidal cells of layer V of the cortex (especially from the motor fields of the frontal lobe: 4, 6aα, 6aβ). These are glutamatergic, strictly ipsilateral fibers with a clear somatotopic organization. There are no feedback pathways from the striatum to the cortex.
- From the substantia nigra: Dopaminergic fibers (nigrostriatal pathway). It is their destruction that triggers parkinsonism.
- From the centromedian nucleus of the thalamus: Presumably, excitatory pathways relaying signals from the cerebellum and reticular formation.
- From the raphe nuclei (nuclei raphes): Serotoninergic fibers.
Efferent pathways of the striatum are formed primarily by GABAergic spiny neurons. They project to the external and internal segments of the globus pallidus, as well as to the pars compacta and pars reticulata of the substantia nigra.
Motor loop and the development of Parkinson's disease
The functioning of the extrapyramidal system is based on complex feedback loops.
The globus pallidus receives a massive amount of information from the striatum (important: the pallidus does not receive direct afferent fibers from the cortex; the cortex sends fibers only to the substantia nigra, red nucleus, and subthalamic nucleus). Then, the globus pallidus sends its efferent fibers to the thalamus. The thalamus relays these impulses back to the cerebral cortex, closing the motor feedback loop.
In Parkinson's disease, dopaminergic neurons of the substantia nigra degenerate. Because of this, dopamine stimulation of the striatum ceases. The loss of this link disrupts the normal operation of the entire motor loop. Interestingly, it was precisely the specific neurological symptoms and clinical picture of Parkinson's disease that served as a key for scientists in understanding the normal physiological function of the nigrostriatal system in healthy individuals.
Briefly: answers to topical questions
Which neurotransmitters are involved in the regulation of the extrapyramidal system and the pathogenesis of Parkinson's disease?
Several key neurotransmitters are involved in the regulation of the extrapyramidal system and the pathogenesis of the disease.
- Dopamine is a modulating neurotransmitter; degeneration of dopaminergic fibers of the nigrostriatal pathway is the cause of Parkinson's disease.
- Glutamate is an excitatory neurotransmitter of the corticostriatal and other pathways.
- GABA is an inhibitory neurotransmitter of the direct and indirect pathways.
- Acetylcholine is an excitatory neurotransmitter; an imbalance between the dopaminergic and cholinergic systems is characteristic of the pathogenesis.
- Substance P and enkephalin act as cotransmitters.
- Serotonin is the neurotransmitter of afferent fibers from the raphe nuclei.
What clinical symptoms form the basis of the clinical picture of Parkinson's disease?
The clinical picture is based on four main motor disorders.
- Hypokinesia is the leading (obligate) manifestation, expressed as stiffness and slowing of movements (oligokinesia and bradykinesia).
- Rigidity is muscle tension.
- Rest tremor is involuntary shaking (most often of the hands resembling "pill-rolling"), disappearing during purposeful movements and during sleep.
- Postural instability refers to postural disorders and difficulties with maintaining balance during standing and walking.
The diagnosis is established in the presence of hypokinesia and at least one more of the listed symptoms.
Specifically which thalamic nuclei relay impulses from the basal ganglia back to the cortex?
Impulses from the basal ganglia are received by specific nuclei of the ventral group of the thalamus.
- Ventral oral anterior nucleus (V.o.a.) receives information from the globus pallidus.
- Ventral anterior nucleus (VA) also receives afferentation from the globus pallidus (globus pallidus).
Subsequently, the thalamus relays impulses to the cerebral cortex (sending glutamatergic fibers), thereby completing the formation of the motor feedback loop.
Which pharmacotherapeutic drug classes are used to treat Parkinson's disease?
The following main drug classes are used for the pharmacotherapy of the disease:
- Dopamine precursors (replacement therapy) — levodopa (L-DOPA).
- Peripheral DOPA decarboxylase inhibitors — carbidopa, benserazide (block the conversion of levodopa to dopamine in the periphery).
- Dopamine receptor agonists — bromocriptine, pramipexole (directly stimulate receptors).
- Dopamine catabolism inhibitors — MAO-B inhibitors (selegiline) and COMT inhibitors (entacapone).
- Anticholinergic agents (central antimuscarinics) — trihexyphenidyl.
- Amantadine is used as adjunctive therapy.
The striatum combines the "tail" and the "putamen" — the caudate nucleus (nucleus caudatus) and the putamen (putamen). It is to these structures that the dopaminergic "parkinsonian" pathways run from the substantia nigra.
Class and exam questions
Which specific cells die in Parkinson's disease?
Degeneration of dopaminergic neurons located in the substantia nigra occurs.
Does the globus pallidus receive direct pathways from the cerebral cortex?
No, the globus pallidus does not receive direct afferent fibers from the cerebral cortex. The bulk of information reaches it from the striatum.
What causes the pigmentation of the substantia nigra?
The dark, saturated color of the substantia nigra is due to a high melanin content. In addition, it (like the globus pallidus and red nucleus) has a high iron content.
Where does the basal ganglia feedback motor loop close?
Impulses travel from the striatum to the globus pallidus, from where the majority of fibers end in the thalamus, and the thalamus then relays impulses back to the cerebral cortex.
What else to study on this topic
- Syntopy of the basal ganglia and lateral ventricles on frontal sections of the brain.
- The role of the medial medullary lamina (lamina medullaris medialis) in the structure of the lenticular nucleus.
- Embryogenesis of the extrapiramidal system: diencephalic origin of the pallidum.
- Somatotopic organization of glutamatergic pathways from the frontal cortex to the striatum.
- Anatomy of the internal capsule and its anterior limb on axial slices.
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