Know Your Brain: Subthalamic Nucleus
September 16, 2020
Where is the subthalamic nucleus?
What is the subthalamic nucleus and what does it do?
The subthalamic nucleus is considered part of the basal ganglia. The basal ganglia are a group of subcortical nuclei that are involved in a variety of cognitive and emotional functions, but are best known for their role in movement. The precise contributions of the basal ganglia to movement still aren’t fully understood, but one popular hypothesis suggests that the basal ganglia play a critical role in facilitating desired movements, while at the same time inhibiting unwanted and/or competing movements. To read more about the basal ganglia and this purported function, see this article.
The subthalamic nucleus is considered a critical component of basal ganglia circuits that are devoted to the suppression of unwanted movements. These inhibitory circuits are known as the indirect pathway and the hyperdirect pathway. In both pathways, the inhibition of movement is thought to be traceable back to excitatory glutamate neurons that extend from the subthalamic nucleus to stimulate GABA neurons in the globus pallidus and substantia nigra; these GABA neurons in turn exert an inhibitory influence over neurons in the thalamus that typically prompt movement when they’re excited.
The subthalamic nucleus’ role in suppressing unwanted movements may be critical even for the simplest movements. If, for example, you are reaching out to pick up a cup of coffee, your brain must not only activate the muscles necessary for the movement, but inhibit those that would counteract the desired movement. Indeed, even when you are sitting still, unwanted movements (like your hand jerking involuntarily up in the air) must continuously be subdued by your brain. It has been hypothesized that the subthalamic nucleus plays an important role in these types of movement inhibition.
It’s important to note, however, that the functions of the subthalamic nucleus (and basal ganglia as a whole) are not limited to movement. Recent research suggests the subthalamic nucleus may also contribute to cognitive functions like decision-making, attention, and working memory (among others). And the subthalamic nucleus may be part of circuits that have important influences on emotion as well.
Some of our understanding of these more extensive roles for the subthalamic nucleus come from studies involving deep brain stimulation, or DBS. DBS is a surgical procedure that involves implanting an electrode in the brain. Once the electrode is in place, it can be prompted to emit electrical impulses that are hypothesized to interfere with neural activity.
DBS has been found to be especially useful in the treatment of Parkinson’s disease. Parkinson’s disease is characterized by movement problems like slow, effortful movement, and difficulty initiating movements. It is believed that some of these movement-related symptoms stem from overactivity in the subthalamic nucleus. This increased subthalamic nucleus activity may lead to excessive inhibition of movement via the basal ganglia circuits mentioned above.
Thus, when the electrode in DBS is positioned in or near the subthalamic nucleus, turning the device on can disrupt the inhibitory actions of the subthalamic nucleus and facilitate movement. To learn more about DBS, see this article.
As mentioned above, the use of DBS has also helped us to appreciate the complexity of the roles of the subthalamic nucleus. Many patients who receive DBS experience not only an improvement of their Parkinsonian symptoms, but also develop side effects that include cognitive and emotional changes like memory disturbances and apathy. It has been proposed that disruption of the function of the subthalamic nucleus might be responsible for these side effects of DBS. It should be said, however, that variability in the side effects of DBS—as well as a poor understanding of exactly how DBS affects brain activity—makes it difficult to say this with certainty.
Regardless, the evidence collected to date suggests that the subthalamic nucleus is an important area of the brain for motor control and a variety of other actions. Future research will be needed, however, to fully understand the functions of this small—but important—collection of neurons.
References (in addition to linked text above):
Bonnevie T, Zaghloul KA. The Subthalamic Nucleus: Unravelling New Roles and Mechanisms in the Control of Action. Neuroscientist. 2019;25(1):48-64. doi:10.1177/1073858418763594
Heida T, Marani E, Usunoff KG. The subthalamic nucleus part II: modelling and simulation of activity. Adv Anat Embryol Cell Biol. 2008;199:1-vii.
Temel Y, Blokland A, Steinbusch HW, Visser-Vandewalle V. The functional role of the subthalamic nucleus in cognitive and limbic circuits. Prog Neurobiol. 2005;76(6):393-413. doi:10.1016/j.pneurobio.2005.09.005