Subthalamic nucleus
Encyclopedia
The subthalamic nucleus is a small lens-shaped nucleus
in the brain
where it is, from a functional point of view, part of the basal ganglia
system. Anatomically, it is the major part of subthalamus
. As suggested by its name, the subthalamic nucleus is located ventral
to the thalamus
. It is also dorsal to the substantia nigra
and medial to the internal capsule
. It was first described by Jules Bernard Luys
in 1865, and the term corpus Luysi or Luys' body is still sometimes used.
found in the subthalamic nucleus has rather long sparsely spiny dendrite
s. The dendritic arborizations are ellipsoid, replicating in smaller dimension the shape of the nucleus. 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 with brain size as well as the external dimensions of the nucleus. The principal neurons are glutamatergic, which give them a particular functional position in the basal ganglia system. In humans there are also a small number (about 7.5%) of GABA
ergic interneuron
s that participate in the local circuitry; however, the dendritic arborizations of subthalamic neurons shy away from the border and majorly interact with one another.
as often said but by radiating fibers crossing the medial pallidum first and the internal capsule (see figure). These afferents are GABAergic, inhibiting neurons in 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 subthalamic nucleus also receives neuromodulatory inputs, notably dopaminergic
axons from the substantia nigra
pars compacta.
It also receives inputs from the pedunculopontine nucleus
.
Some researchers have reported internal axon
collaterals. However, there is little functional evidence for this.
Several recent studies have focused on the autonomous pacemaking ability of subthalamic neurons. These cells are often referred to as "fast-spiking pacemakers", since they can generate spontaneous action potential
s at rates of 80 to 90 Hz in primates.
. Both are fast-spiking pacemakers. Together, they are thought to constitute the "central pacemaker of the basal ganglia" 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 measures 808 mm³, the subthalamic nucleus only 158 mm³. This translated in numbers of neurons represents a strong compression with loss of map precision.
Some axons from the lateral pallidum go to the striatum. The activity of the medial pallidum is influenced by afferences from the lateral pallidum and from the subthalamic nucleus. The same for the nigra reticulata. 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
.
(DBS), is used to treat patients with Parkinson disease. 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, that the stimulus also causes nearby astrocytes to release Adenosine Triphosphate
(ATP), a precursor to adenosine (through a catabolic process). In turn, adenosine A1 receptor activation depresses excitatory transmission in the thalamus, thus mimicking ablation
of the subthalamic nucleus.
.
control system which may perform action selection. STN dysfunction has also been shown to increase impulsivity in individuals presented with two equally rewarding stimuli.
Nucleus (neuroanatomy)
In neuroanatomy, a nucleus is a brain structure consisting of a relatively compact cluster of neurons. It is one of the two most common forms of nerve cell organization, the other being layered structures such as the cerebral cortex or cerebellar cortex. In anatomical sections, a nucleus shows up...
in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
where it is, from a functional point of view, part of the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
system. Anatomically, it is the major part of subthalamus
Subthalamus
The subthalamus is a part of the diencephalon. Its major part is the subthalamic nucleus. Functionally, it also encompasses the globus pallidus, which is topographically part of the telencephalon.-Anatomy:...
. As suggested by its name, the subthalamic nucleus is located ventral
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
to the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
. It is also dorsal to the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
and medial to the internal capsule
Internal capsule
The internal capsule is an area of white matter in the brain that separates the caudate nucleus and the thalamus from the lenticular nucleus. The internal capsule contains both ascending and descending axons....
. It was first described by Jules Bernard Luys
Jules Bernard Luys
Jules Bernard Luys was a French neurologist who made important contributions to the fields of neuroanatomy and neuropsychiatry....
in 1865, and the term corpus Luysi or Luys' body is still sometimes used.
Structure
The principal type of neuronNeuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
found in the subthalamic nucleus has rather long sparsely spiny dendrite
Dendrite
Dendrites are the branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project...
s. The dendritic arborizations are ellipsoid, replicating in smaller dimension the shape of the nucleus. 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 with brain size as well as the external dimensions of the nucleus. The principal neurons are glutamatergic, which give them a particular functional position in the basal ganglia system. In humans there are also a small number (about 7.5%) of GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
ergic interneuron
Interneuron
An interneuron is a multipolar neuron which connects afferent neurons and efferent neurons in neural pathways...
s that participate in the local circuitry; however, the dendritic arborizations of subthalamic neurons shy away from the border and majorly interact with one another.
Afferent axons
The subthalamic nucleus receives its main input from the globus pallidus, not so much through the ansa lenticularisAnsa lenticularis
The ansa lenticularis is a part of the brain, making up the superior layer of the substantia innominata of Meynert...
as often said but by radiating fibers crossing the medial pallidum first and the internal capsule (see figure). These afferents are GABAergic, inhibiting neurons in the subthalamic nucleus. Excitatory, glutamatergic inputs come from the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
(particularly the motor cortex), and from the pars parafascicularis of the central complex. The subthalamic nucleus also receives neuromodulatory inputs, notably dopaminergic
Dopaminergic
Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
axons from the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
pars compacta.
It also receives inputs from the pedunculopontine nucleus
Pedunculopontine nucleus
The pedunculopontine nucleus is located in the brainstem, caudal to the substantia nigra and adjacent to the superior cerebellar peduncle. It has two divisions, one containing cholinergic neurons, the pars compacta, and one containing mostly glutamatergic neurons, the pars dissipata...
.
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. 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. 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).Some researchers have reported internal axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
collaterals. 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. 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", since they can generate spontaneous action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
s at rates of 80 to 90 Hz in primates.
Lateropallido-subthalamic system
Strong reciprocal connections link the subthalamic nucleus and the external segment of the globus pallidusGlobus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
. Both are fast-spiking pacemakers. Together, they are thought to constitute the "central pacemaker of the basal ganglia" with synchronous bursts.
The connection of the lateral pallidum with the subthalamic nucleus is also the one in the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
system where the reduction between emitter/receiving elements is likely the strongest. In terms of volume, in humans, the lateral pallidum measures 808 mm³, the subthalamic nucleus only 158 mm³. This translated in numbers of neurons represents a strong compression with loss of map precision.
Some axons from the lateral pallidum go to the striatum. The activity of the medial pallidum is influenced by afferences from the lateral pallidum and from the subthalamic nucleus. The same for the nigra reticulata. 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
Parkinson's disease is a degenerative disorder of the central nervous system...
.
Pathophysiology and interventions
Chronic stimulation of the STN, called deep brain stimulationDeep brain stimulation
Deep brain stimulation is a surgical treatment involving the implantation of a medical device called a brain pacemaker, which sends electrical impulses to specific parts of the brain...
(DBS), is used to treat patients with Parkinson disease. 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, that the stimulus also causes nearby astrocytes to release Adenosine Triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
(ATP), a precursor to adenosine (through a catabolic process). In turn, adenosine A1 receptor activation depresses excitatory transmission in the thalamus, thus mimicking ablation
Ablation
Ablation is removal of material from the surface of an object by vaporization, chipping, or other erosive processes. This occurs in spaceflight during ascent and atmospheric reentry, glaciology, medicine, and passive fire protection.-Spaceflight:...
of the subthalamic nucleus.
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 hemiballismusHemiballismus
Hemiballismus is a very rare movement disorder. It is 500 times rarer than Parkinson's disease. Its effects can sometimes be severe enough to prevent patients from being able to perform daily functions. It is usually associated with structural brain lesions but can occur with metabolic abnormalities...
.
Function
The function of the STN is unknown, but current theories place it as a component of the basal gangliaBasal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
control system which may perform action selection. STN dysfunction has also been shown to increase impulsivity in individuals presented with two equally rewarding stimuli.
External links
- http://isc.temple.edu/neuroanatomy/lab/atlas/pdhn/