Subthalamic Nucleus

The subthalamic nucleus (STN) is a small lens-shaped structure, part of the basal ganglia, located in the diencephalon region of the brain. It's situated inferior to the thalamus, lateral to the hypothalamus, medial to the internal capsule, and ventral to the substantia nigra. If you were to look at a coronal section of the brain, the hypothalamus would be found centrally (or medially), while the subthalamic nucleus would be towards the side (or laterally), below the substantia nigra^[1].

The STN primarily consists of glutamatergic neurons, meaning these neurons release the excitatory neurotransmitter glutamate. It is one of the few excitatory structures within the largely inhibitory basal ganglia system. In addition to glutamatergic neurons, the STN also contains GABAergic interneurons and a smaller percentage of other types of neurons^[3].

The STN receives inputs primarily from the cortex and the globus pallidus internus (GPi). The projections from the cortex are glutamatergic, providing excitatory inputs. Projections from the GPi, on the other hand, are GABAergic and therefore inhibitory. The STN also sends efferent projections to structures such as the GPi and the globus pallidus externus (GPe), both of which are major components of the basal ganglia^[1].

Functionally, the STN plays a critical role in motor control through its integration in the basal ganglia circuitry. It is a key component in both the indirect and hyperdirect pathways of the basal ganglia, contributing to the balance between movement initiation (excitation) and suppression (inhibition)^[4].

Below you will find a simplified explanation.

Indirect Pathway

This pathway serves an inhibitory function, meaning it suppresses or limits movement. In this pathway, the STN is activated by the globus pallidus externus (GPe). When the GPe is inhibited (e.g., when a movement needs to be suppressed), it reduces its inhibitory influence on the STN. As a result, the activity of the STN increases, which in turn excites the output nuclei of the basal ganglia (the internal segment of the globus pallidus and the substantia nigra pars reticulata). These output nuclei then inhibit the thalamus, leading to a reduction in motor activity^[4].

Hyperdirect Pathway

This pathway provides a rapid means of stopping an initiated movement. It involves direct excitatory input from the cortex to the STN. When a movement needs to be stopped quickly, the cortex sends a signal to the STN, which then excites the basal ganglia output nuclei. This increases their inhibitory effect on the thalamus, which in turn quickly reduces motor activity^[5].

Therefore, the STN plays a central role in modulating motor activity, contributing to both the suppression of unnecessary or unwanted movements and the rapid halting of initiated movements.

While the STN's involvement in the basal ganglia and motor control is often the focus of study, it is also involved in many other systems and functions within the brain, including emotion, cognition, sleep, and pain^[7].

1. Limbic System: The STN is thought to be involved in the limbic system, which is involved in emotion, motivation, and reward processing. There are connections between the limbic-associated areas of the cortex and the STN, and changes in the STN have been implicated in psychiatric conditions, including obsessive-compulsive disorder and depression.

2. Cognitive Functions: The STN has also been implicated in certain cognitive functions, including decision making and conflict resolution. The 'hyperdirect' pathway from the frontal areas of the cortex to the STN allows for rapid transmission of signals that can influence cognitive processes.

3. Sleep Regulation: The STN has been found to have connections to the pedunculopontine nucleus and laterodorsal tegmental nucleus, which are key parts of the brain's arousal and sleep regulation systems.

4. Pain Perception: The STN also has connections to the periaqueductal gray and other areas involved in pain perception, suggesting it may play a role in modulating the perception of pain.