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Brain: Subthalamic nucleus
Coronal slices of human brain showing the basal ganglia, subthalamic nucleus (STN) and substantia nigra (SN). The basal ganglia (or basal nuclei) are a group of nuclei in the Brain interconnected with the Cerebral cortex, Thalamus and The substantia nigra ( Latin for "black substance" Sömmering) or locus niger is a heterogeneous portion of the midbrain, separating
DA-loops in Parkinson's disease
Latin nucleus subthalamicus
Part of Basal ganglia
NeuroNames hier-418
MeSH Subthalamic+Nucleus
Dorlands/Elsevier n_11/14166739

The subthalamic nucleus is a small lens-shaped nucleus in the brain where it is a part of the basal ganglia system. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's Latin ( lingua Latīna, laˈtiːna is an Italic language, historically spoken in Latium and Ancient Rome. The basal ganglia (or basal nuclei) are a group of nuclei in the Brain interconnected with the Cerebral cortex, Thalamus and NeuroNames is a system of nomenclature for the human and/or macaque Brain. Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Elsevier, the world's largest Publisher of Medical and Scientific literature, forms part of the Reed Elsevier group In Neuroanatomy, a nucleus is a Central nervous system structure that is composed mainly of Gray matter, and that acts as a hub or transit point for The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain The basal ganglia (or basal nuclei) are a group of nuclei in the Brain interconnected with the Cerebral cortex, Thalamus and As suggested by its name, the subthalamic nucleus is located ventral to the thalamus. In fields of Anatomy, anatomical terms of location are descriptive terms to help identify relative positions or directions within a species The thalamus (from Greek θάλαμος = room chamber, IPA= /ˈθæləməs/ is a pair and symmetric part of the brain It is also dorsal to the substantia nigra and medial to the internal capsule. The substantia nigra ( Latin for "black substance" Sömmering) or locus niger is a heterogeneous portion of the midbrain, separating The internal capsule is an area of White matter in the Brain that separates the Caudate nucleus and the Thalamus from the Lenticular nucleus It was first described by Jules Bernard Luys in 1865,[1] and the term corpus Luysi or Luys' body is still sometimes used. Jules Bernard Luys (1828&ndash1897 was a French Neurologist who made important contributions to the fields of Neuroanatomy and Neuropsychiatry

Contents

Anatomy

Structure

The principal type of neuron found in the subthalamic nucleus has rather long dendrites devoid of spines . Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information Dendrites (from Greek δένδρον déndron, “tree” are the branched projections of a Neuron that act to conduct the electrochemical The dendritic arborizations are ellipsoid, replicating in smaller dimension the shape of the nucleus. [2] The dimensions of these arborizations (1200,600 and 300 μm) are similar across many species—including rat, cat, monkey and man—which is unusual. However, the number of neurons increases across evolution as well as the external dimensions of the nucleus. Due to the bending of dendrites at the border, the subthalamic nucleus is a close nucleus, able to receive information only in its space. The principal neurons are glutamatergic, which give them a particular functional position in the basal ganglia system. Glutamic acid (abbreviated as Glu or E) is one of the 20 Alpha Amino acids It is not among the human Essential amino acids Its In humans there are also a small number (about 7. 5%) of GABAergic interneurons that participate in the local circuitry. Gamma-aminobutyric acid (GABA is the chief inhibitory Neurotransmitter in the Mammalian Central nervous system. An interneuron (also called association neuron, local circuit neuron or relay neuron) is a neuron which connects Afferent neurons and Efferent [3]

Afferent axons

The subthalamic nucleus receives its main input from the lateral pallidum ( external segment of the globus pallidus) (84. The globus pallidus ( Latin for "pale globe" is a sub- cortical structure of the Brain. 2% of its axons[4]), not so much through the ansa lenticularis as often said but by radiating fibers crossing the medial pallidum first and the internal capsule (see figure). This afference is GABAergic, inhibiting the neurons of the subthalamic nucleus. Excitatory, glutamatergic inputs come from the cerebral cortex (particularly the motor cortex), and from the pars parafascicularis of the central complex. The cerebral cortex is a structure within the Brain that plays a key role in Memory, Attention, perceptual Awareness, Thought, The subthalamic nucleus also receives neuromodulatory inputs, notably dopaminergic axons from the substantia nigra pars compacta. In neuroscience neuromodulation is the process in which several classes of Neurotransmitters in the nervous system regulate diverse populations of Neurons (one Dopaminergic means "related to the Neurotransmitter Dopamine " The substantia nigra ( Latin for "black substance" Sömmering) or locus niger is a heterogeneous portion of the midbrain, separating [5]

Efferent targets

The axons of subthalamic nucleus neurons leave the nucleus dorsally. The efferent axons are glutamatergic (excitatory). Except for the connection to the striatum (17. 3% in macaques), most of the subthalamic principal neurons are multitargets and directed to the other elements of the core of the basal ganglia. [4] Some send axons to the substantia nigra medially and to the medial and lateral nuclei of the pallidum laterally (3-target, 21. 3%). Some are 2-target with the lateral pallidum and the substantia nigra (2. 7%) or the lateral pallidum and the medial (48%). Less are single target for the lateral pallidum. In the pallidum, subthalamic terminals end in bands parallel to the pallidal border. [6][7] When all axons reaching this target are added, the main afference of the subthalamic nucleus is, in 82. 7% of the cases, clearly the medial pallidum (internal segment of the globus pallidus). The globus pallidus ( Latin for "pale globe" is a sub- cortical structure of the Brain.

Some researchers have reported internal axon collaterals. An axon or nerve fiber is a long slender projectionof a nerve cell or Neuron, that conducts electrical impulses away from the neuron's Cell [8] However, there is little functional evidence for this.

Physiology

Subthalamic nucleus

The first intracellular electrical recordings of subthalamic neurons were performed using sharp electrodes in a rat slice preparation (Nakanishi et al. , 1987). In these recordings three key observations were made, all three of which have dominated subsequent reports of subthalamic firing properties. The first observation was that, in the absence of current injection or synaptic stimulation, the majority of cells were spontaneously firing. The second observation is that these cells are capable of transiently firing at very high frequencies. The third observation concerns non-linear behaviors when cells are transiently depolarized after being hyperpolarized below –65mV. They are then able to engage voltage-gated calcium and sodium currents to fire bursts of action potentials.

Several recent studies have focused on the autonomous pacemaking ability of subthalamic neurons. These cells are often referred to as "fast-spiking pacemakers",[9] since they can generate spontaneous action potentials at rates of 80 to 90Hz in primates. In Neurophysiology, the action potential is a self-regenerating Wave of Electrochemical activity that allows Nerve cells to carry a signal

Lateropallido-subthalamic system

Strong reciprocal connections link the subthalamic nucleus and the external segment of the globus pallidus. Both are fast-spiking pacemakers. Together, they are thought to constitute the "central pacemaker of the basal ganglia"[10] with synchronous bursts.

The connection of the lateral pallidum with the subthalamic nucleus is also the one in the basal ganglia system where the reduction between emitter/receiving elements is likely the strongest. In terms of volume, in humans, the lateral pallidum mesures 808 mm³, the subthalamic nucleus only 158 mm³. [11] This translated in numbers of neurons represents a strong compression with loss of map precision.

The systemic position of this circuit is particular in the basal ganglia system that may be revealed by contrast versus outputs subsystems. There are two output paths starting from the striatum. The first has a first relay in the medial pallidum (GABAegic inhibitory) and the second in the nigra reticulata (GABA). These two output subsystems do not send regulatory messages to other elements of the basal ganglia system: striatum, lateral pallidum or subthalamic nucleus. The lateropallido-subthalamic subsystem is particular in that it does the reverse. It does not send axons to the thalamus and from there to the cortex. All efferent axons of the subsystem are indeed returning inside the basal ganglia system. This topologically makes it a regulator. Some axons from the lateral pallidum go to the striatum. [12] The activity of the medial pallidum is influenced by afferences from the lateral pallidum and from the subthalamic nucleus. [13] The same for the nigra reticulata. [7] The subthalamic nucleus sends axons to another regulator: the pedunculo-pontine complex (id).

The lateropallido-subthalamic system is thought to play a key role in the generation of the patterns of activity seen in Parkinson's disease. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's [14]

Physiopathology and interventions

Chronic stimulation of the STN, called deep brain stimulation (DBS), is used to treat patients with Parkinson disease. In Neurotechnology, deep brain stimulation ( DBS) is a surgical treatment involving the implantation of a medical device called a Brain pacemaker Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's The first to be stimulated are the terminal arborisations of afferent axons which modifies the activity of subthalamic neurons. However, it has been shown in thalamic slices from mice[15], that the stimulus also causes nearby astrocytes to release Adenosine Triphosphate (ATP), a precursor to adenosine (through a catabolic process). Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy Adenosine is a Nucleoside composed of a Molecule of Adenine attached to a Ribose sugar molecule ( Ribofuranose) moiety via a β-N9- In turn, adenosine A1 receptor activation depresses excitatory transmission in the thalamus, thus mimicking ablation of the subthalamic nucleus. Ablation is defined as the removal of material from the surface of an object by Vaporization, Chipping, or other erosive processes

Pathology

Unilateral destruction or disruption of the subthalamic nucleus – which can commonly occur via a small vessel stroke in patients with diabetes, hypertension, or a history of smoking – produces hemiballismus. Hemiballismus is a Neurological sign that presents as a Movement disorder, characterised by unilateral wild large Amplitude flinging movements of the arm

Function

The function of the STN is unknown, but current theories place it as a component of the basal ganglia control system which may perform action selection. The basal ganglia (or basal nuclei) are a group of nuclei in the Brain interconnected with the Cerebral cortex, Thalamus and STN dysfunction has also been shown to increase impulsivity in individuals presented with two equally rewarding stimuli. [16]

Additional images

Coronal section of brain immediately in front of pons.

References

  1. ^ Luys, Jules Bernard (1865). Jules Bernard Luys (1828&ndash1897 was a French Neurologist who made important contributions to the fields of Neuroanatomy and Neuropsychiatry Recherches sur le système cérébro-spinal, sa structure, ses fonctions et ses maladies (in French). Paris: Baillière.  
  2. ^ Yelnik, J. & Percheron, G. (1979). "Subthalamic neurons in primates : a quantitative and comparative anatomy". Neuroscience 4 (11): 1717–1743. doi:10.1016/0306-4522(79)90030-7. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 117397.  
  3. ^ Levesque J. C. & Parent A. (2005). "GABAergic interneurons in human subthalamic nucleus". Movement Disorders 20 (5): 574–584. doi:10.1002/mds.20374. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15645534.  
  4. ^ a b Sato F. ; Parent M. ; Levesque M. ; & Parent A. (2000). "Axonal branching pattern of neurons of the subthalamic nucleus in primates". Journal of Comparative Neurology 424 (1): 142–152. doi:10.1002/1096-9861(20000814)424:1<142::AID-CNE10>3.0.CO;2-8. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 10888744.  
  5. ^ Cragg S. J. ; Baufreton J. ; Xue Y. ; Bolam J. P. ; & Bevan M. D. (2004). "Synaptic release of dopamine in the subthalamic nucleus". European Journal of Neuroscience 20 (7): 1788–1802. doi:10.1111/j.1460-9568.2004.03629.x. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15380000.  
  6. ^ Nauta, H. J. W. & Cole, M. (1978). "Efferent projections of the subthalamic nucleus : an autoradiographic study in monkey and cat". Journal of Comparative Neurology 180 (1): 1–16. doi:10.1002/cne.901800102. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 418083.  
  7. ^ a b Smith, Y. ; Hazrati, L-N. & Parent, A. (1990). "Efferent projections of the subthalamic nucleus in the squirrel monkey as studied by the PHA-L anterograde tracing method". Journal of Comparative Neurology 294 (2): 306–323. doi:10.1002/cne.902940213. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 2332533.  
  8. ^ Kita, H. ; Chang, H. T. ; & Kitai, S. T. (1983). "The morphology of intracellularly labeled rat subthalamic neurons: A light microscopic analysis". Neuroscience 215 (3): 245–257. PMID 6304154.  
  9. ^ Surmeier D. J. ; Mercer J. N. ; & Chan C. S. (2005). "Autonomous pacemakers in the basal ganglia: who needs excitatory synapses anyway?". Current Opinion in Neurobiology 15 (3): 312–318. doi:10.1016/j.conb.2005.05.007. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15916893.  
  10. ^ Plenz, D. & Kitai, S. T. (1999). "A basal ganglia pacemaker formed by the subthalamic nucleus and external globus pallidus". Nature 400 (6745): 677–682. doi:10.1038/23281. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 10458164.  
  11. ^ Yelnik, J. (2002). "Functional anatomy of the basal ganglia". Movement Disorders 17 (Suppl. 3): S15–S21. doi:10.1002/mds.10138. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11948751.  
  12. ^ Sato, F. ; Lavallée, P. ; Levesque, M. & Parent, A. (2000). "Single-axon tracing study of neurons of the external segment of the globus pallidus in primate". Journal of Comparative Neurology 417 (1): 17–31. doi:10.1002/(SICI)1096-9861(20000131)417:1<17::AID-CNE2>3.0.CO;2-I. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 10660885.  
  13. ^ Smith, Y. ; Wichmann, T. & DeLong, M. R. (1994). "Synaptic innervation of neurones in the internal pallidal segment by the subthalamic nucleus and the external pallidum in monkeys". Journal of Comparative Neurology 343 (2): 297–318. doi:10.1002/cne.903430209. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 8027445.  
  14. ^ Bevan M. D. ; Magill P. J. ; Terman D. ; Bolam J. P. ; & Wilson CJ. (2002). "Move to the rhythm: oscillations in the subthalamic nucleus-external globus pallidus network". Trends in Neurosciences 25 (10): 525–531. doi:10.1016/S0166-2236(02)02235-X. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12220881.  
  15. ^ Bekar L. , Libionka W. , Tian G. , Xu Q. , Torres A. , Wang X. , Lovatt D. , Williams E. , Takano T. , Schnermann J. , Bakos R. , Nedergaard M. (2008). "Adenosine is crucial for deep brain stimulation–mediated attenuation of tremor". Nature Medicine 14 (1): 75–80. doi:10.1038/nm1693. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  
  16. ^ Frank, M. ; Samanta, J. ; Moustafa, A. ; Sherman, S. (2007). "Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism". Science 318 (5854): 1309-12. doi:10.1126/science.1146157. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17962524.  

See also

External links

The primate basal ganglia system is a symmetrical major cerebral system that has only recently been recognized
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