Normal movement involves changes in posture, maintenance of balance, and mechanisms that place the limbs and fingers precisely where they are needed. The basal ganglia are responsible for the planning, initiation, sequencing and smooth coordination of muscular activity.
The inputs to the corpus striatum arise from the cerebral cortex. Information is fed by direct or indirect pathways to the globus pallidus interna, where it is relayed to the thalamus and onwards to the cortex.
The indirect pathway involves reciprocal connections between the globus pallidus and the subthalamic nucleus.
The dopaminergic pathway from the substantia nigra to the striatum facilitates the direct pathway, but inhibits the indirect pathway. This nigro-striatal pathway degenerates in Parkinson's disease.
Deep Brain Stimulation is a technique for applying electrical stimuli to small regions of the brain. Deep Brain Stimuation of the Globus Pallidus Interna, Subthalamic Nucleus or Thalamus are used as a treatment of Parkinson's Disease.
The Basal Ganglia: Corpus Striatum, Globus Pallidus, Substantia Nigra, Subthalamic Nucleus; Deep Brain Stimulation
Circuitry of the Basal Ganglia
The Corpus Striatum and Substantia Nigra
The Striatum reeives inputs from the cerebral cortex; these are excitatory and use Glutamate as neurotransmitter.
These inputs keep the striatum informed about the full range of information concerning the current position and movements of the body.
The Corpus Striatum and the Globus Pallidus interna are connected using two parallel routes, one direct, and the other indirect.
The Globus Pallidus Interna is the origin of the output pathway of the basal ganglia and projects to the thalamus and onwards to the cerebral cortex.
The direct projection from the Striatum to the Globus Pallidus Interna is known as the Direct Pathway. The striatum also has reciprocal connections with the substantia nigra, the source of dopaminergic endings in the striatum (the nigro-striatal pathway).
the nigro-striatal neurones originate from the pars compacta of the substantia nigra
The Globus Pallidus has reciprocal links with the Subthalamic nucleus; the pathway from the GPe to the subthalamic nucleus and onwards to the GPi is known as the Indirect Pathway.
The pathways originating in the striatum and globus pallidus are inhibitory and GABA-ergic.
Image source: Gray's Anatomy
The diagram shows a transverse section of the brainstem. Histochemical studies of the cells show different bands of cells within the substantia nigra, one of which, the pars compacta, contains dopamine. These neurones are the orgin of the nigro-stiatal pathway. Note also the midline raphe nucleus, the origin of neurones containing 5-hydroxytryptamine (5-HT).
The Substantia Nigra and its connections with the Striatum
The Striatum has reciprocal connections with the substantia nigra, so called because of the dark colour of some of its neurones. These neurones form the pars compacta of the midbrain and are dopaminergic neurones. They project to the striatum - the nigro-striatal pathway - and release dopamine, which modulates the GABA-ergic networks of the striatum.
Another part of the substantia nigra - the pars reticulata - receives inputs from the striatum.
When the substantia nigra degenerates in Parkinson's disease, the balance is upset, as a result of the degeneration and loss of dopaminergic neurones, which have important and opposing actions on the direct and indirect pathways (see below).
This imbalance results in alternating rhythmic movements of the musculature when at rest, i.e. in the absence of voluntary movement.
Image source: brothersdiamond.wordpress.com
Note the opposing effects of the dopaminergic input form the substantia nigra on the Direct and Indirect pathways. This is the result of the presence of dopamine D1 receptors in the Direct Pathway, and of D2 receptors in the Indirect Pathway.
Actions of Dopamine in the Striatum
The actions of dopamine in the striatum can be excitatory or inhibitory, depending on the type of receptor on the neurones that receive a dopaminergic input.
agonists of Dopamine 1 receptors excite neurones; striatal neurones in the Direct pathway are excited by dopaminergic terminals of the nigro-striatal neurones
agonists of Dopamine 2 receptors inhibit neurones; striatal neurones in the Indirect pathway are inhibited by dopaminergic terminals of the nigro-striatal neurones
As a result, the direct pathway is facilitated and the indirect pathway is inhibited by dopamine release by the substantia nigra, and normal smooth movements occur as a result of the balance between these two effects.
The diagram shows that the output of the basal ganglia relays in the thalamus, and is directed to the supplementary motor area. Putamen=Corpus Striatum; GPe= Globus Pallidus Externa; GPi= Globus Pallidus Interna.
Note that the thalamic nuclei are subject to the opposing effects of the direct and indirect pathways. An imbalance in this system is believed to be responsible for the neurological changes seen in Parkinson's Disease.
Connections between the Globus Pallidus and the Subthalamic Nucleus
The important Subthalamic Nucleus, receives inputs from the association cortex and from the striatum (using a relay in the globus pallidus externa). This is part of the indirect pathway.
The subthalamic nucleus and the globus pallidus externa both project to the globus pallidus interna.
The subthalamic nucleus is important because it has a high level of intrinsic activity, and this dominates motor activity when the substantia nigra degenerates in Parkinson's Disease.
One of the major roles of the basal ganglia is not only to initiate movements but to produce a smooth sequence of movements.
The reciprocal nigro-striatal and pallido-subthalamic connections have opposing effects on movement, and the balance between the two generates smooth movements.
Deep Brain Stimulation (DBS) is a technique that uses electrical stimuli to the globus Pallidus, subthalamic nucleus or thalamus of patients with Parkinson's Disease to help control Parkinsonian symptoms. DBS is preferred to lesions of the globus pallidus (pallidotomy), as it is more versatile, does not do permanent damage to the brain, and can be varied as the disease progresses. See http://emedicine.medscape.com/article/1965354-overview for a recent review.
Opposing Actions of the Direct and Indirect Pathways
The Direct and Indirect pathways converge on GPi neurones that project to the thalamus and release GABA.
Both pathways are excited by the glutamatergic input from pre-motor and supplementary motor areas, but they respond differently to dopamine (released by nigro-striatal neurones).
The direct pathway facilitates the thalamic neurones by removing GABA-ergic inhibition on GPi neurones.
The indirect pathway increases inhibition of thalamic neurones because glutamatergic subthalamic neurones excite GP interna neurones (which release GABA in the thalamus).
In normal individuals there appears to be a balance in this relationship, and an imbalance is thought to result in the motor changes seen in Parkinson's Disease.
The direct pathway involves glutamergic afferents from the cortex exciting medium spiny neurones in the striatum; these inhibit GABAergic neurones in the Globus Pallidus interna, which in turn inhibit the thalamic neurones that return to the cortex. So the effect of the direct pathways is disinhiition - i.e. removal of inhibition from the thalamic nuclei.
The indirect pathway has an additional relay in the subthalamic nucleus as shown opposite, which has excitatory effects on the GABAergic neurones that pass from the Globus Pallidus interna to the thalamus. So its effects on the thalamic nuclei are to increase inhibition.
Lack of dopamine within the striatum in Parkinson's disease has the consequence that the normal disinhibition (i.e. reduction in the inhibitory GABA-ergic influence) in the direct pathway is greatly reduced, or absent, so the balance changes in favour of subthalamic nucleus and the indirect pathway.