Basal ganglia, their connections and function, parkinsonism

The basal ganglia or nuclei are heavily interconnected and play an important role in motor planning and modulation. By choosing the intended movement, the basal ganglia use different pathways to initiate and terminate the motor program, by controlling the muscle tone, muscle length, speed, and strength of the movement by using the pyramidal system as the executor.

Beyond motor control, the basal ganglia also plays crucial roles in various cognitive and emotional processes, including decision-making, procedural learning, and emotional regulation.

Basal ganglia

The major structures that compose the basal ganglia are:

• the striatum (Str), which includes the caudate nucleus and the putamen,
• the globus pallidus (GP) which is divided into two segments, the internal (GPi) and external parts (GPe),
• the subthalamic nucleus (STN)
• the substantia nigra (SN) which is also divided into two parts, the reticular part (SNr) and the compact part (SNc).

Direct pathway

The direct pathway starts from the cortex and projects to the striatum (caudate nucleus and putamen) with excitatory glutamatergic (glu) neurons. The neurons from the striatum, which are inhibitory GABAergic, send their axons to the medial (internal) globus pallidus and substantia nigra, pars reticulata (SNr).

The neurons from the internal globus pallidus and SNr send their axons to the thalamus, and they are also inhibitory. The fibers that travel from the pallidum to the thalamus, form two white matter fascicles called ansa lenticularis and lenticular fasciculus, that fuse into one pathway called thalamic fasciculus just before they enter the thalamus.

From the thalamus, excitatory pathways go to the cortex (prefrontal, premotor and supplementary cortex) where they affect the planning of the movement by synapsing with the neurons of the corticospinal and corticobulbar tracts in the brainstem and spinal cord.

So the final function of the direct pathway of the basal ganglia is to excite the motor cortex or to increase the motor activity.

Indirect pathway

This pathway begins (like the direct pathway) from the cortex, projecting to the striatum. Instead of sending axons directly to the GPi and SNr, they project to the external globus pallidus.

The neurons from the GPe send inhibitory fibers to the subthalamic nucleus instead of sending directly to the thalamus (hence its name “indirect”). From the subthalamic nucleus, neurons send their axons to the GPi/SNr and then continue as the direct pathway with GABAergic inhibitory neurons to the thalamus and glutamate excitatory efferents to the cortex.

The final result of this pathway is a decreased activity of the cortical motor neurons and consequential suppression of the extemporaneous movement.

Hyperdirect pathway

The hyperdirect pathway consists of neurons projecting from the cortex directly to the subthalamic nucleus (STN). Those fibers convey strong excitatory signals to the GPi/SNr with shorter conduction time than the direct and indirect pathway, bypassing the striatum.

When receiving glutamatergic inputs from the cerebral cortex directly to the subthalamic nucleus, it then excites the GPi/SNr thus suppressing thalamic activity on the cerebral cortex and increasing inhibitory influences on the upper motor neurons. As a result, together with the indirect pathway, only the selected motor program is executed and other competing motor programs are canceled.

The neuronal circuits that modulate the function of the basal ganglia are:

• The nigrostriatal pathway
• The thalamostriatal pathway

Nigrostriatal pathway

This pathway projects from the substantia nigra pars compacta to the striatum, and it utilizes the neurotransmitter dopamine. This pathway has a modulatory effect on the basal ganglia, with dopamine facilitating the motor loop in these two ways:

• It excites the direct pathway
• It inhibits the indirect pathway

The different effect on the direct and indirect pathway is explained by the activation of the different dopamine receptors that are located within the neurons of the striatum. There are two types of dopamine receptors, D1 and D2, which respond differently when stimulated with dopamine. Stimulation of D1 results with the excitation of the neuron, while the stimulation D2 results with inhibition.

D1 receptors are found on the striatal neurons that give rise to the direct pathway. On the other hand, D2 receptors are found on the neurons whose axons form the indirect pathway. So the final effect of the nigrostriatal pathway is the promotion of the direct pathway and at the same time the inhibition of the indirect pathway. The activity of the neurons within the pars compacta substantia nigra is related to the reward system and behavioral stimuli, so it is thought that they play a role in some forms of motor learning.

Thalamostriatal pathway

These fibers arise from the intralaminar nuclei of the thalamus and terminate primarily in the striatum. Besides that, some fibers terminate in the globus pallidus and in the subthalamic nucleus.

Parkinson's disease

Parkinsonism

Parkinson’s disease is the most prevalent disorder associated with basal ganglia. It is the result of the degeneration of the dopaminergic neurons of the pars compacta of the substantia nigra. This is actually the place of origin of the nigrostriatal pathway that is essential for the promotion of the direct pathway of the basal ganglia. Because of its damage, the excitation of the supplementary motor area which is of key significance for the movement planning is lost.

Symptoms include:

Akinesia

Hypokinesia

Tremor

Walking Gait etc.

Citations:

https://www.kenhub.com/en/library/anatomy/direct-and-indirect-pathways-of-the-basal-ganglia