The globus pallidus (GP) is one of the components of basal ganglia. It divides into globus pallidus internus (GPi) and globus pallidus externus (GPe). The globus pallidus and putamen collectively form the lentiform (lenticular) nucleus, which lies beneath the insula. The globus pallidus, caudate, and putamen form corpus striatum. The corpus striatum is also an important part of basal ganglia. The thalamus, subthalamus, and substantia nigra (SN) are not a part of basal ganglia but serve essential functions for the network.

The motor system controlled by basal ganglia is made of corticobulbar and subcortical structures, the gray matter of the spinal cord, cerebellum, and efferent nerves. The basal ganglia coordinate with other structures in the brain to plan and implement goal-oriented behaviors. This co-ordination requires multiple striatal (motor), cognitive, and limbic (reward) circuits and pathways. The globus pallidus can modulate these pathways because of its connections. The major output of striatum is through the GPe. The GPi acts as the final output for both direct and indirect pathways of the basal ganglia network. The thalamus, however, is slightly different. It acts as a relay because of its reciprocal interconnections with cortical and subcortical structures. Therefore, the thalamus can perform multiple motor and sensory functions. These unique characteristics enable each component to work effectively.

The dysfunction of the GP has been noted in ischemia, alcohol, and opiate abuse. This dysfunction gives rise to various cognitive and motor problems.

The GP is a subcortical structure of the brain. It is a triangular mass of cells located medial to the putamen. The pale appearance of the GP is due to the myelinated axons that make up the structure; this is in contrast with the unmyelinated structures (putamen and striatum), which appear darker. The medial medullary lamina of the white matter divides the GP to globus pallidus internus (GPi) and globus pallidus externus (GPe).[1] The GPi is the medial subdivision, whereas GPe is the lateral subdivision. The GPe is relatively larger than GPi. It is also located caudomedially to the corpus striatum.[2]

The main function of the globus pallidus is to control conscious and proprioceptive movements. The GPe is the intrinsic nucleus, whereas the GPi is the output nucleus. The intrinsic nucleus acts as a relay for information. The output nucleus, primarily, sends information to the thalamus.[3] To perform its function effectively, the GP receives input from multiple structures. The GP receives the majority of the inhibitory input (GABAergic) from the striatum. It is important to note that substantia nigra pars compacta (SNPc) has projections to the striatum. These projections secrete dopamine to target either D1 or D2 receptors present on the striatum. D1 receptors are excitatory (glutamatergic) in nature, whereas D2 receptors are inhibitory in nature.[4] Some inhibitory input (GABAergic) also comes from the caudate and putamen. The output is computed through the direct and indirect pathways.

The ‘direct pathway’ promotes movement. The SNPc excites the striatum by secreting dopamine (nigrostriatal projections) to activate the D1 striatal receptors. The excited D1 receptors activate the striatum, and more inhibitory signals are sent to the GPi. A few inhibitory signals transmit simultaneously to the substantia nigra pars reticularis (SNPr). As a result, the GPi and SNPr experience inhibition. The GPi and SNPr lose their inhibitory influence on the thalamic nuclei (ventral anterior thalamic nucleus and ventral lateral thalamic nucleus). This loss of influence means that the thalamic nuclei are no longer inhibited and can send excitatory signals to the motor cortex via corticospinal projections. Ultimately, the excitation of the motor cortex allows the required movement to occur. It is important to note that GPi secretes an opiate known as substance-P, which may regulate the nigrostriatal pathway.[5]

The ‘indirect pathway’ limits motor function so that excessive and erratic movements do not occur. The SNPc inhibits the striatum by secreting dopamine (nigrostriatal projections) to activate D2 striatal receptors, which means that the inhibited D2 receptors send less inhibitory signals to GPe. The GPe is in a relatively excited state. Therefore, it sends more inhibitory signals to the subthalamic nucleus. The inhibited subthalamic nucleus can no longer inhibit the GPi and the SNPr. The GPi and the SNPr are, therefore, able to inhibit the thalamic nuclei. Ultimately, the thalamic nuclei inhibit movement. In recent experiments, the GPe secrete an opiate called enkephalin.[6] This opiate can modulate the nigrostriatal pathway.[7]

These pathways, therefore, explain how the GPe and the GPi differ in their functions.

Human brain development begins during the third week of gestation from the ectoderm. The notochord induces neurulation, a process by which ectoderm above the notochord forms neuroectoderm to give rise to other structures. As a result, the neural tube begins to form. The brain continues to develop from the neural tube. Following the closure of this neural tube by week 6, the primary brain vesicles form. These primary brain vesicles include the prosencephalon (forebrain), mesencephalon (midbrain), and rhombencephalon (hindbrain).[8] These primitive brain vesicles continue to differentiate into different structures. In the fifth week of gestation, the prosencephalon develops into the telencephalon and the diencephalon. The telencephalon has dorsal and ventral parts. The dorsal telencephalon gives rise to the cerebral cortex, whereas the ventral telencephalon gives rise to the basal ganglia.[9] Thus, it is from the ventral telencephalon that the GP develops.

The GP receives its blood supply from the anterior choroidal artery (AChA), middle cerebral artery (MCA), and anterior cerebral artery (ACA). The MCA provides the majority of the blood supply. The perforating branches of the ACA supply the anterior and inferior portion of the GP. The perforating arteries from the MCA perfuse the majority of the superior and posterior portion of the lateral section of the GP. Heubner’s artery and ACA also supply [10][11] A small portion of the lateral segment of the GP. The AChA perfuses the medial portion of the GP.[10]

The venous drainage of the GP derives from veins that drain the adjacent basal ganglia, particularly caudate and putamen. The system forms from a deep and ventricular group of veins. The deep group subdivides into a group of inferior striate veins that drain the putamen and caudate nuclei. The deep group of veins joins the deep middle cerebral and basal veins. The ventricular group of veins drains the caudate nucleus. The ventricular group joins the internal cerebral and basal veins.[11] The basal and internal cerebral veins join to form the great vein of Galen, which then drains into the straight sinus.

The GP, as a part of basal ganglia, has a similar lymphatic drainage system as the cerebral cortex. The lymphatic system of the cerebral cortex forms from perivascular, cerebrospinal fluid (CSF), and olfactory drainage pathways as well as meningeal lymphatic vessels.[12][13]However, a study mentions that the perivascular spaces in the basal ganglia and cerebral cortex are structurally different. This difference is partly responsible for the difference in fluid composition between the two.[14]

The globus pallidus, being a part of basal ganglia, plays an additional role in higher cognitive functions such as reinforcement and memory building. The nuclei (including GP) and cortical areas interconnect via independent parallel loop circuits. The association and limbic cortices project to specific striatal domains, which, in turn, project back to the corresponding cortical areas via the globus pallidus and the thalamus. There have also been suggestions that the location of both the GP and substantia nigra helps in the transmission of information from the limbic to the associative system.[15]