The external segment of the globus pallidus (GPe) is a crucial nuclei in the basal ganglia that plays a fundamental role in motor control, action selection, and movement regulation. GPe neurons serve as a central hub in the indirect pathway, receiving inhibitory input from the striatum and providing inhibitory output to the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi).[1] This page provides comprehensive information about GPe neuron morphology, neurophysiology, molecular characteristics, circuit function, and relevance to neurodegenerative diseases including Parkinson's disease and Huntington's disease.
The globus pallidus external segment (GPe) is one of the two segments of the globus pallidus, the other being the internal segment (GPi). Located in the basal ganglia, the GPe acts as a major relay station that modulates motor behavior through its extensive connections with striatal medium spiny neurons (MSNs), the subthalamic nucleus, and the internal pallidal segment.[2] The GPe is primarily composed of GABAergic neurons that utilize gamma-aminobutyric acid as their primary neurotransmitter, providing tonic inhibition to downstream targets.[3]
| Taxonomy | ID | Name / Label |
|---|---|---|
| Allen Brain Cell Atlas | Search | Globus Pallidus External Segment Neurons |
| Cell Ontology (CL) | Search | Check classification |
| Human Cell Atlas | Search | Check expression data |
| CellxGene Census | Search | Check cell census |
GPe neurons exhibit distinctive morphological features that enable their functional roles in basal ganglia circuits:
These morphological characteristics support the high-frequency firing patterns and integration of synaptic inputs that define GPe neuronal activity.[4]
GPe neurons demonstrate unique electrophysiological properties that distinguish them from other basal ganglia neurons:
GPe neurons receive synaptic inputs from multiple sources:
GPe neurons express a characteristic combination of molecular markers that define their identity:
The GPe occupies a pivotal position in basal ganglia circuitry, particularly within the indirect pathway that regulates movement suppression and action selection.
In the classical indirect pathway model:
This indirect pathway functions to suppress unwanted movements by increasing GPe activity, which then inhibits downstream motor structures. The GPe also sends projections back to the striatum (arkypallidal neurons), forming feedback loops that modulate the direct and indirect pathways.[7]
For more details on these pathways, see Direct Pathway Medium Spiny Neurons and Indirect Pathway Medium Spiny Neurons, as well as the Basal Ganglia Direct and Indirect Pathway overview.
Emerging research reveals that GPe contains functionally distinct neuron populations:
This heterogeneity suggests more complex computational roles than previously appreciated.[8]
Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to profound alterations in basal ganglia function including GPe activity:
GPe involvement in Huntington's disease (HD) is particularly interesting given the early degeneration of striatal MSNs:
| Source | Neurotransmitter | Effect |
|---|---|---|
| Striatum (indirect pathway) | GABA | Inhibitory |
| Striatum (direct pathway) | GABA | Inhibitory |
| Subthalamic nucleus | Glutamate | Excitatory |
| Cerebral cortex | Glutamate | Excitatory (indirect) |
| Substantia nigra pars compacta | Dopamine | Modulatory |
| Target | Neurotransmitter | Effect |
|---|---|---|
| Subthalamic nucleus | GABA | Inhibitory |
| Internal globus pallidus (GPi) | GABA | Inhibitory |
| Striatum (arkypallidal) | GABA | Inhibitory |
| Nucleus accumbens | GABA | Inhibitory |
Changes in GPe neuronal activity can serve as biomarkers for certain neurological conditions. Electrophysiological recordings from the GPe during stereotactic neurosurgery for movement disorders provide valuable diagnostic information about underlying pathophysiology.
The GPe has been investigated as a potential target for surgical interventions in movement disorders:
The globus pallidus external segment represents a critical node in the basal ganglia circuitry that governs motor behavior and action selection. Understanding GPe neuron biology is essential for comprehending the pathophysiology of movement disorders including Parkinson's disease and Huntington's disease, and for developing novel therapeutic interventions.
Parent A, Hazrati LN. Functional anatomy of the basal ganglia. 1995. ↩︎
Kita H. Network properties and function of the external pallidal segment: input-output organization of GPe neurons. 2007. ↩︎
Fulton S, Kazdo M, Sadikot AF. GABAergic neurons in the rat globus pallidus. 2010. ↩︎
Cooper AJ, Stanford IM. Electrophysiological and morphological characteristics of three subtypes of rat globus pallidus neurone in vitro. 2000. ↩︎
Ramanathan S, Hanley JJ, Deniau JM, Bolam JP. Synaptic convergence of motor and somatosensory cortical inputs onto GPe neurons. 2002. ↩︎
Bevan MD, Wilson CJ, Bolam JP, Magill PJ. Equilibrium potential of GPe neurons and its contribution to basal ganglia output. 2006. ↩︎
Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. 1989. ↩︎
Mallet N, Micklem BR, Acsády L, et al. Arkypallidal neurons project to striatum in the basal ganglia. 2012. ↩︎
Bergman H, Wichmann T, Karmon B, DeLong MR. The primate subthalamic nucleus. 1994. ↩︎
Vatsavai PK, O'Leary H, Ghods Z, et al. Globus pallidus external segment neurons in Huntington's disease. 2018. ↩︎