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Lateral Globus Pallidus

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Lateral globus pallidus (GPE) seen in 2nd image from the left

The lateral globus pallidus (or external globus pallidus, GPe) combines with the medial globus pallidus to form the globus pallidus, an anatomical subset of the basal ganglia. Globus pallidus means "pale globe" in Latin, indicating its appearance. The lateral globus pallidus is the segment of the globus pallidus that is relatively further (lateral) from the midline of the brain.

The lateral globus pallidus contains GABAergic neurons, which allow for its inhibitory function. The lateral globus pallidus' GABAergic neurons extend axons to the subthalamic nucleus (in the dicencephalon), the striatum, medial globus pallidus and substantia nigra pars reticulata.[1]

GPe is particular in comparison to the other elements of the basal ganglia by the fact that it does not work as an output base of the basal ganglia but as a main regulator of the basal ganglia system.

Function

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Direct and indirect striatopallidal pathways: Glutamatergic pathways are red, dopaminergic are magenta and GABAergic pathways are blue. STN: Subthalamic Nucleus SNr: Substantia Nigra pars reticulata SNc: Substantia Nigra pars compacta GPi: Medial globus pallidus

Indirect Striatopallidal Pathway

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The basal ganglia functions to tonically inhibit movement, mainly in the absence of motor cortex command, via GABAergic inhibition of the ventral lateral nucleus and ventral anterior nucleus of the thalamus, as well as the superior colliculus and mesopontine tegmentum of the brain stem. When movement is required, the cerebral cortex sends commands to the striatum, which directly inhibits the medial globus pallidus and substantia nigra pars reticulata, decreasing thalamus and brainstem inhibition[2]. As the pathway from the striatum to the medial globus pallidus is monosynaptic (containing one synapse), it is called the Direct Striatopallidal Pathway.

The Indirect Striatopallidal Pathway, which contains the lateral globus pallidus and the subthalamic nucleus, functions to modulate the effects of the Direct Striatopallidal Pathway. The lateral globus pallidus acts as a inhibitory "control device", adjusting subthalamic nucleus neuronal activity via GABAergic output. [3].

When movement adjustment is required, striatal inhibitory GABAergic axons are sent to the lateral globus pallidus, decreasing inhibition of the subthalamic nucleus. The subthalamic nucleus' glutamatergic neurons then stimulate the Medial globus pallidus and substantia nigra pars reticulata.

This multisynaptic indirect striatopallidal pathway allows for regulated excitatory input from the subthalamic nucleus to the Medial globus pallidus and substantia nigra pars reticulata. This combines with Direct Striatopallidal Pathway inhibition in the medial globus pallidus, allowing for fine tuned basal ganglia output, and more controlled movement.

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Lateral globus pallidus dysfunction has been observed in the following conditions:

Medial Globus Pallidus

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Medial globus pallidus (GPI) is seen in the 2nd image from the left

The medial globus pallidus (or internal, GPi) combines with the lateral globus pallidus to form the globus pallidus, an anatomical subset of the basal ganglia. Globus pallidus means "pale globe" in Latin, indicating its appearance. The medial globus pallidus is the segment of the globus pallidus that is relatively closer (medial) to the midline of the brain.

The medial globus pallidus contains GABAergic neurons, which allow for its inhibitory function. As the medial globus pallidus, along with the substantia nigra pars reticulata, forms the output of the basal ganglia, these neurons extend to the thalamus, the centromedian complex and the pedunculopontine complex[1].

Function

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Direct and indirect striatopallidal pathways: Glutamatergic pathways are red, dopaminergic are magenta and GABAergic pathways are blue. STN: Subthalamic Nucleus SNr: Substantia Nigra pars reticulata SNc: Substantia Nigra pars compacta GPe: Lateral globus pallidus

The medial globus pallidus acts to tonically inhibit the ventral lateral nucleus and ventral anterior nucleus of the thalamus. As these two nuclei are needed for movement planning, this inhibition restricts movement initiation and prevents unwanted movements.

The Direct Striatopallidal Pathway

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The medial globus pallidus receives inhibitory GABAergic signals from the striatum when a movement requirement is signaled from the cerebral cortex. As the medial globus pallidus is one of the direct output centers of the basal ganglia, this causes disinihibtion of the thalamus, increasing overall ease of initiating and maintaining movement. As this pathway only contains one synapse (from the striatum to the medial globus pallidus), it is considered a direct pathway.[5]

The Direct Striatopallidal Pathway is modulated by stimulation of the medial globus pallidus by the lateral globus pallidus and subthalamic nucleus, via the Indirect Striatopallidal Pathway.[3]

Clinical Significance

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Pathology

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Dysfunction of the medial globus pallidus has been correlated to the following conditions:

Deep brain stimulation

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Deep brain stimulation (DBS) is a treatment by which regulated electrical pulses are sent to specifically targeted areas, and has been used on the medial globus pallidus to treat a variety of medical conditions.

DBS has been applied to patients with Tardive Dyskinesia, and the majority saw more than 50% improvement in symptoms[9]. Tourette Syndrome patients have also benefited from this treatment, showing over 50% improvement in tic severity (compulsive disabling motor tics are symptoms of Tourette patients)[8]. The medial globus pallidus is also considered a "highly effective target for neuromodulation" when using deep brain stimulation on Parkinson's Disease patients[6].

References

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  1. ^ a b Schroll, Henning; Hamker, Fred H. (2013-01-01). "Computational models of basal-ganglia pathway functions: focus on functional neuroanatomy". Frontiers in Systems Neuroscience. 7: 122. doi:10.3389/fnsys.2013.00122. PMC 3874581. PMID 24416002.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  2. ^ Parent, André; Hazrati, Lili-Naz (1995-01-01). "Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop". Brain Research Reviews. 20 (1): 91–127. doi:10.1016/0165-0173(94)00007-C.
  3. ^ a b Parent, André; Hazrati, Lili-Naz (1995-01-01). "Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidium in basal ganglia circuitry". Brain Research Reviews. 20 (1): 128–154. doi:10.1016/0165-0173(94)00008-D.
  4. ^ Hegeman, Daniel J.; Hong, Ellie S.; Hernández, Vivian M.; Chan, C. Savio (2016-05-01). "The external globus pallidus: progress and perspectives". European Journal of Neuroscience. 43 (10): 1239–1265. doi:10.1111/ejn.13196. ISSN 1460-9568. PMC 4874844. PMID 26841063.
  5. ^ Morita, Makiko; Hikida, Takatoshi (2015-11-01). "[Distinct roles of the direct and indirect pathways in the basal ganglia circuit mechanism]". Nihon Shinkei Seishin Yakurigaku Zasshi = Japanese Journal of Psychopharmacology. 35 (5–6): 107–111. ISSN 1340-2544. PMID 26785520.
  6. ^ a b Andrade, Pablo; Carrillo-Ruiz, José D.; Jiménez, Fiacro (2009-07-01). "A systematic review of the efficacy of globus pallidus stimulation in the treatment of Parkinson's disease". Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia. 16 (7): 877–881. doi:10.1016/j.jocn.2008.11.006. ISSN 0967-5868. PMID 19398341.
  7. ^ Waldvogel, Henry J.; Kim, Eric H.; Tippett, Lynette J.; Vonsattel, Jean-Paul G.; Faull, Richard LM (2014-01-01). Nguyen, Hoa Huu Phuc; Cenci, M. Angela (eds.). Behavioral Neurobiology of Huntington's Disease and Parkinson's Disease. Current Topics in Behavioral Neurosciences. Springer Berlin Heidelberg. pp. 33–80. doi:10.1007/7854_2014_354. ISBN 9783662463437.
  8. ^ a b Dong, S.; Zhuang, P.; Zhang, X.-H.; Li, J.-Y.; Li, Y.-J. (2012-01-01). "Unilateral deep brain stimulation of the right globus pallidus internus in patients with Tourette's syndrome: two cases with outcomes after 1 year and a brief review of the literature". The Journal of International Medical Research. 40 (5): 2021–2028. ISSN 1473-2300. PMID 23206487.
  9. ^ a b Spindler, Meredith A.; Galifianakis, Nicholas B.; Wilkinson, Jayne R.; Duda, John E. (2013-02-01). "Globus pallidus interna deep brain stimulation for tardive dyskinesia: case report and review of the literature". Parkinsonism & Related Disorders. 19 (2): 141–147. doi:10.1016/j.parkreldis.2012.09.016. ISSN 1873-5126. PMID 23099106.