Globus Pallidus (External)

The external globus pallidus, also called the globus pallidus externus (GPe) or external pallidal segment, is the lateral division of the globus pallidus and an important component of the basal ganglia. It lies deep within each cerebral hemisphere and forms part of the lentiform nucleus together with the internal globus pallidus and putamen.

The external globus pallidus consists predominantly of inhibitory GABAergic neurons. It is extensively interconnected with the striatum, subthalamic nucleus, internal globus pallidus, substantia nigra, and other components of the basal ganglia. In the classical model of basal ganglia circuitry, it occupies a central position in the indirect pathway.

Unlike the internal globus pallidus, which serves as one of the principal output nuclei of the basal ganglia, the external segment functions mainly as an intrinsic processing nucleus. Its neurons are tonically active and exert continuous inhibitory influences on several basal ganglia targets, particularly the subthalamic nucleus.

Location

The external globus pallidus lies deep within the cerebral hemisphere as the lateral segment of the globus pallidus.

It is positioned medial to the putamen and lateral to the internal globus pallidus. Together, the putamen and globus pallidus form the lentiform nucleus.

The internal capsule lies medial to the lentiform nucleus and separates it from structures including the caudate nucleus and thalamus.

General Features

Feature	Description
Full name	External globus pallidus
Alternative term	Globus pallidus externus (GPe)
Location	Deep cerebral hemisphere
Position	Between putamen and internal globus pallidus
Major neurotransmitter	GABA
Major classical pathway	Indirect basal ganglia pathway
Important target	Subthalamic nucleus
General role	Intrinsic regulation and coordination of basal ganglia activity

Globus Pallidus

The globus pallidus is a pale-appearing mass of gray matter located medial to the putamen.

It is divided by a thin medullary lamina into an external segment and an internal segment.

Although the two segments are adjacent anatomically, their connections and functional roles within basal ganglia circuitry differ substantially.

External and Internal Segments

The external globus pallidus is the more lateral pallidal division, while the internal globus pallidus (GPi) occupies the medial portion.

The GPe functions primarily as an intrinsic basal ganglia relay and regulatory structure. The GPi, in contrast, is one of the principal output nuclei of the basal ganglia.

Both contain predominantly GABAergic neurons and exhibit substantial spontaneous neuronal activity.

External versus Internal Globus Pallidus

Feature	External Globus Pallidus	Internal Globus Pallidus
Abbreviation	GPe	GPi
Position	Lateral pallidal segment	Medial pallidal segment
Principal neurotransmitter	GABA	GABA
Classical role	Intrinsic component of indirect pathway	Major basal ganglia output nucleus
Important target	Subthalamic nucleus	Thalamus
Direct thalamic output	Not a principal output pathway	Prominent

Relationship to the Putamen

The putamen lies immediately lateral to the external globus pallidus.

A thin lamina of white matter, the lateral medullary lamina, separates the putamen from the globus pallidus.

Functionally, the putamen is part of the striatum and provides major inhibitory input to pallidal structures.

Relationship to the Internal Globus Pallidus

The internal globus pallidus lies immediately medial to the external segment.

The two pallidal segments are separated by the medial medullary lamina.

Connections between the GPe, GPi, subthalamic nucleus, and striatum contribute to the integrated processing performed by basal ganglia networks.

Relationship to the Lentiform Nucleus

The lentiform nucleus is formed by the putamen and globus pallidus.

In a lateral-to-medial direction, its major components are the putamen, external globus pallidus, and internal globus pallidus.

This organization is particularly apparent in coronal and horizontal sections through the basal ganglia.

Relationship to the Internal Capsule

The internal capsule lies medial to the lentiform nucleus and therefore medial to the globus pallidus.

It contains densely packed projection fibers connecting the cerebral cortex with the thalamus, brainstem, and spinal cord.

The close relationship between the pallidum and internal capsule is clinically important because lesions affecting the deep basal ganglia may extend into major motor and sensory projection pathways.

Relationship to the Subthalamic Nucleus

The subthalamic nucleus is one of the most important functional partners of the external globus pallidus.

The GPe sends strong inhibitory GABAergic projections to the subthalamic nucleus, while the subthalamic nucleus sends excitatory glutamatergic projections back to the GPe.

These reciprocal connections create a dynamic network involved in controlling activity throughout the basal ganglia.

Microscopic Organization

The external globus pallidus contains neuronal cell bodies interspersed with numerous myelinated fibers passing through or around the nucleus.

The abundance of myelinated fibers contributes to the relatively pale appearance that gave the globus pallidus its name.

Most projection neurons within the GPe use GABA and therefore exert inhibitory effects on their targets.

GABAergic Neurons

Gamma-aminobutyric acid (GABA) is the principal neurotransmitter used by projection neurons of the external globus pallidus.

GPe neurons inhibit several basal ganglia structures, including the subthalamic nucleus and other pallidal or nigral targets.

This inhibitory signaling is essential for controlling the timing and magnitude of activity within basal ganglia circuits.

Tonic Activity

Many neurons of the external globus pallidus are spontaneously active even in the absence of immediate excitatory input.

This tonic activity allows the GPe to maintain ongoing inhibitory control over its targets.

Changes in GPe firing can therefore regulate downstream structures through either increased inhibition or relative disinhibition.

Afferent Connections

The external globus pallidus receives major input from the striatum and subthalamic nucleus.

Striatal projections to the GPe are predominantly inhibitory and GABAergic, whereas projections from the subthalamic nucleus are excitatory and glutamatergic.

Additional connections arise from other basal ganglia and brainstem structures.

Striatopallidal Pathway

The striatopallidal pathway consists of inhibitory projections from the striatum to the globus pallidus.

Within the classical indirect pathway, a population of striatal medium spiny neurons projects prominently to the external globus pallidus.

Activation of these neurons suppresses GPe activity and alters the inhibitory influence exerted by the GPe on the subthalamic nucleus.

Striatal Input

The striatum consists principally of the caudate nucleus and putamen.

Medium spiny projection neurons provide GABAergic input to the GPe and are themselves influenced by excitatory cortical and thalamic inputs and modulatory dopaminergic signals.

This arrangement allows cortical information to influence pallidal activity indirectly through the striatum.

Subthalamic Input

The subthalamic nucleus sends glutamatergic excitatory projections to the external globus pallidus.

The GPe simultaneously sends inhibitory projections back to the subthalamic nucleus.

This reciprocal organization allows both structures to influence the temporal pattern and synchronization of basal ganglia activity.

Efferent Connections

The external globus pallidus sends inhibitory projections to multiple components of the basal ganglia.

The subthalamic nucleus is a major target, but GPe neurons also communicate with the internal globus pallidus, substantia nigra, striatum, and other regions.

These extensive connections indicate that the GPe functions as more than a simple relay within a single linear pathway.

Pallidosubthalamic Pathway

The pallidosubthalamic pathway carries inhibitory GABAergic projections from the GPe to the subthalamic nucleus.

Under resting conditions, tonic GPe activity helps suppress subthalamic neuronal activity.

Reduction of GPe activity can disinhibit the subthalamic nucleus, allowing its excitatory output to increase.

Connections with the Internal Globus Pallidus

The external globus pallidus influences the internal globus pallidus through both direct and indirect network interactions.

Some GPe neurons provide inhibitory projections to the GPi, while additional influence occurs through the subthalamic nucleus.

These connections allow the external segment to regulate one of the principal output structures of the basal ganglia.

Connections with the Substantia Nigra

The external globus pallidus has connections with components of the substantia nigra.

These interactions contribute to the broader network linking the striatum, pallidum, subthalamic nucleus, and substantia nigra.

The substantia nigra pars reticulata, like the GPi, serves as a major output structure of the basal ganglia.

Indirect Pathway

The external globus pallidus occupies a central position in the classical indirect basal ganglia pathway.

A simplified sequence is:

Cerebral cortex → striatum → external globus pallidus → subthalamic nucleus → internal globus pallidus/substantia nigra pars reticulata → thalamus → cerebral cortex.

The interactions along this pathway include both excitatory and inhibitory synapses.

Functional Logic of the Indirect Pathway

In the classical model, cortical excitation activates striatal neurons participating in the indirect pathway.

These neurons inhibit the GPe, reducing its inhibitory effect on the subthalamic nucleus. The resulting disinhibition increases activity of the subthalamic nucleus.

The subthalamic nucleus then excites basal ganglia output nuclei, increasing their inhibitory influence on selected thalamic targets.

Indirect Pathway Neurotransmitters

Connection	Principal Neurotransmitter	Effect
Cortex → Striatum	Glutamate	Excitatory
Striatum → GPe	GABA	Inhibitory
GPe → Subthalamic nucleus	GABA	Inhibitory
Subthalamic nucleus → GPi/SNr	Glutamate	Excitatory
GPi/SNr → Thalamus	GABA	Inhibitory

Dopaminergic Modulation

Dopamine from the substantia nigra pars compacta modulates striatal neurons participating in basal ganglia pathways.

Neurons associated with the classical indirect pathway predominantly express D2-type dopamine receptors.

Dopaminergic signaling therefore indirectly influences external pallidal activity by modifying the activity of striatal neurons projecting to the GPe.

Direct and Indirect Pathways

The classical direct and indirect pathways provide a useful framework for understanding basal ganglia organization, but they operate as parts of a highly interconnected network rather than as completely independent linear circuits.

The direct pathway largely bypasses the GPe and projects from the striatum toward the GPi and substantia nigra pars reticulata.

The indirect pathway prominently incorporates the GPe and subthalamic nucleus before influencing basal ganglia output nuclei.

Hyperdirect Pathway

The hyperdirect pathway provides a more direct route from the cerebral cortex to the subthalamic nucleus.

Subthalamic neurons can then excite the GPi and substantia nigra pars reticulata, rapidly modifying basal ganglia output.

Because the GPe is reciprocally connected with the subthalamic nucleus, activity within the hyperdirect pathway can also influence external pallidal networks.

Modern View of GPe Function

Modern anatomical and physiological studies indicate that the GPe is not simply an intermediate relay in the indirect pathway.

Its neurons form extensive local and long-range connections with the striatum, subthalamic nucleus, other pallidal regions, substantia nigra, and additional neural structures.

The GPe therefore acts as an important regulatory hub capable of coordinating activity across multiple basal ganglia circuits.

Functional Heterogeneity

Neurons within the external globus pallidus are not a single uniform population.

Different neuronal populations have distinct molecular characteristics, firing patterns, afferent inputs, and projection targets.

This heterogeneity supports the view that the GPe participates in several functional networks rather than performing one isolated function.

Motor Function

The external globus pallidus contributes to the regulation of movement through its position within basal ganglia circuits.

It helps regulate the activity of the subthalamic nucleus and basal ganglia output structures, thereby influencing thalamocortical and brainstem motor systems.

Its role is primarily modulatory and regulatory rather than directly responsible for generating muscle contraction.

Action Selection

Basal ganglia networks contribute to action selection by facilitating contextually appropriate actions while suppressing competing actions.

The external globus pallidus participates in this process by regulating activity within indirect and interconnected basal ganglia pathways.

Its widespread inhibitory projections allow it to influence the balance between competing neural activity patterns.

Movement Suppression

The classical indirect pathway is often described as contributing to suppression of competing or unwanted motor programs.

The GPe is central to this process because inhibition of GPe neurons can disinhibit the subthalamic nucleus and thereby increase activity of basal ganglia output nuclei.

Actual motor control depends on the coordinated activity of direct, indirect, hyperdirect, and other basal ganglia circuits.

Cognitive and Behavioral Functions

Basal ganglia circuits are organized into motor, associative, and limbic territories.

The external globus pallidus participates not only in motor networks but also in circuits associated with cognition, motivation, and behavior.

These functions arise through parallel loops connecting different cortical regions with corresponding regions of the striatum, pallidum, thalamus, and related structures.

Blood Supply

The external globus pallidus receives blood from small penetrating arteries supplying the deep structures of the cerebral hemisphere.

Important contributions arise from lenticulostriate branches of the middle cerebral artery and branches associated with the anterior choroidal arterial circulation.

Individual vascular territories overlap and show anatomical variation.

Lenticulostriate Arteries

The lenticulostriate arteries arise predominantly from the middle cerebral artery and penetrate the anterior perforated substance to supply portions of the basal ganglia and internal capsule.

Branches supply regions of the putamen and globus pallidus as well as neighboring deep structures.

Because these are small penetrating vessels, vascular disease can produce focal lesions involving pallidal and capsular tissue.

Anterior Choroidal Artery

The anterior choroidal artery usually arises from the internal carotid artery and supplies several deep cerebral structures.

Its territory includes portions of the globus pallidus and internal capsule, although the precise distribution varies and overlaps with neighboring arterial territories.

Lesions in this vascular territory can therefore affect multiple functionally distinct structures.

Venous Drainage

Venous drainage from the globus pallidus enters the deep cerebral venous system.

Small deep veins drain toward larger veins associated with the basal ganglia, thalamus, and ventricular region.

These vessels ultimately contribute to the internal cerebral veins and related deep venous channels.

Clinical Significance

Parkinson Disease

Parkinson disease is characterized primarily by degeneration of dopaminergic neurons in the substantia nigra pars compacta.

Loss of dopamine alters activity within striatal pathways and produces major downstream changes in the external globus pallidus, subthalamic nucleus, internal globus pallidus, and related structures.

Abnormal firing patterns and synchronization within this network contribute to the motor manifestations of Parkinson disease.

Indirect Pathway in Parkinson Disease

In the classical model, reduced dopaminergic stimulation increases the influence of D2-associated indirect-pathway striatal neurons.

Greater inhibition of the GPe reduces its inhibitory effect on the subthalamic nucleus. Increased subthalamic activity then enhances excitatory drive to the GPi and substantia nigra pars reticulata.

This increases inhibitory basal ganglia output and contributes to reduced facilitation of movement.

Huntington Disease

Early Huntington disease prominently affects populations of striatal neurons associated with the indirect pathway.

Loss of inhibitory striatal input can increase GPe activity, which increases inhibition of the subthalamic nucleus and alters downstream basal ganglia output.

This disruption contributes to the excessive involuntary movements characteristic of the early stages of the disease.

Hemiballismus

Hemiballismus is classically associated with lesions involving the contralateral subthalamic nucleus or its functional connections.

Because the GPe and subthalamic nucleus are strongly and reciprocally connected, disruption of this network alters activity reaching basal ganglia output nuclei.

The resulting reduction in inhibitory control of motor systems can contribute to large-amplitude involuntary movements.

Pallidal Lesions

Lesions involving the external globus pallidus can disturb basal ganglia network activity.

Clinical effects depend on whether the lesion is focal or bilateral, its precise location, and whether adjacent structures such as the putamen, GPi, or internal capsule are also involved.

Possible manifestations include abnormalities of movement, muscle tone, behavior, or cognition.

Vascular Lesions

Small-vessel ischemia or hemorrhage can affect the globus pallidus and neighboring basal ganglia structures.

Because several deep nuclei and the internal capsule are closely packed, vascular lesions often involve more than one anatomical structure.

Clinical findings therefore depend heavily on lesion extent and associated capsular involvement.

Hypoxic and Metabolic Injury

The globus pallidus can be affected in certain forms of hypoxic, toxic, and metabolic brain injury.

Some disorders produce characteristic bilateral abnormalities within pallidal structures on neuroimaging.

The distribution of injury varies according to the underlying mechanism and should be interpreted together with other affected brain regions.

Neuroimaging

The external globus pallidus can be identified on MRI by its position between the putamen and internal pallidal segment.

Coronal and axial images are particularly useful for demonstrating the organization of the lentiform nucleus and its relationship to the internal capsule.

High-resolution imaging can distinguish pallidal segments and reveal structural or signal abnormalities associated with neurological disease.

Deep Brain Stimulation

The globus pallidus is an important region in functional neurosurgery.

The internal globus pallidus, rather than the external segment, is a major established target for deep brain stimulation in selected movement disorders.

However, understanding the anatomy of the GPe is essential for accurate localization because it lies immediately lateral to the GPi and forms part of the same pallidal complex.

Sectional Anatomy

In coronal sections, the external globus pallidus appears as a wedge-shaped region of gray matter medial to the putamen and lateral to the internal pallidal segment.

The medullary laminae help distinguish the individual components of the lentiform nucleus.

Recognition of this lateral-to-medial sequence is useful when interpreting neuroanatomical sections and MRI.

Developmental Anatomy

The globus pallidus develops as part of the basal telencephalic and related forebrain systems that give rise to the deep nuclei of the cerebral hemisphere.

Its developmental relationships differ in some respects from those of the striatum, despite the close anatomical association of the pallidum and putamen in the adult brain.

Maturation of pallidal connections contributes to the development of integrated basal ganglia circuits.

Anatomical Variation

The size, shape, and precise boundaries of the external globus pallidus vary among individuals.

Its general position between the putamen and internal globus pallidus remains consistent.

The vascular territories supplying the GPe also vary because penetrating arterial distributions overlap considerably within the basal ganglia.

Functional Importance

The external globus pallidus is a central regulatory component of the basal ganglia. Through its tonic inhibitory activity and extensive connections, it regulates the subthalamic nucleus and interacts with striatal, pallidal, and nigral structures.

Although traditionally emphasized as an intermediate component of the indirect pathway, the GPe is now understood as a highly interconnected intrinsic basal ganglia nucleus with heterogeneous neuronal populations and multiple functional roles.

The external globus pallidus therefore contributes to movement regulation, action selection, suppression of competing actions, coordination of basal ganglia activity, and the integration of motor, cognitive, and behavioral information.