wiki笔记：subthalamic nucleus--2022/2/9

Subthalamic nucleus

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Subthalamic nucleus

 

Coronal slices of human brain showing the basal ganglia (external globus pallidus (GPe) and internal globus pallidus (GPi)), subthalamic nucleus (STN) and substantia nigra (SN).

 

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. In terms of anatomy, it is the major part of the 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,[1] and the term corpus Luysi or Luys' body is still sometimes used.

Contents

· 1Anatomy

· 1.1Structure

· 1.2Afferent axons

· 1.3Efferent targets

· 2Physiology

· 2.1Subthalamic nucleus

· 2.2Lateropallido-subthalamic system

· 3Pathophysiology

· 4Function

· 5Additional images

· 6See also

· 7References

Anatomy[edit]

Structural connectivity of the human subthalamic nucleus as visualized through diffusion-weighted MRI.

Structure[edit]

The principal type of neuron found in the subthalamic nucleus has rather long, sparsely spiny dendrites.[2][3] In the more centrally located neurons, the dendritic arbors have a more ellipsoidal shape.[4] The dimensions of these arbors (1200 μm, 600 μm, and 300 μm) are similar across many species—including rat, cat, monkey and human—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 GABAergic interneurons that participate in the local circuitry; however, the dendritic arbors of subthalamic neurons shy away from the border and primarily interact with one another.[5]

Afferent axons[edit]

The subthalamic nucleus receives its main input from the external globus pallidus (GPe),[6] 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). These afferents are GABAergic, inhibiting neurons in the subthalamic nucleus. Excitatory, glutamatergic inputs come from the cerebral cortex (particularly the motor cortex)

(这句话非常重要。我研究分析判断的结果是motor cortex中的BA4 cortex投射到subthalamic nucleus，而BA6 cortex不投射到subthalamic nucleus。)

(皮层到subthalamic nucleus的这个投射，很有可能是对动作结束的精准控制，毕竟subthalamic nucleus兴奋reticulata和internal globus pallidus的效果是去抑制丘脑的VA、VL以及让眼球不动。当然，subthalamic nucleus出现大面积地兴奋导致了悲伤的情绪感受，这样的悲伤情绪状态是可以自己消亡的，因为reticulata抑制了pars compacta，从而减少了dorsal striatum对external globus pallidus的抑制性输出，这样external globus pallidus会自动放电去抑制subthalamic nucleus；接受疼痛信息的central median nucleus in the intralaminar 同时投射到putamen和subthalamic nucleus，让internal globus pallidus同时接收抑制型递质和兴奋型递质，正负离子同时大量进入细胞，大概这对neuron来说是个不健康的状态吧，这或许是疼痛所带来的不可忍受的原因吧，然后主观意识也可以自我选择是让internal globus pallidus兴奋或者抑制，痛的时候似乎眼球也不能转动。好在可以通过magnus raphe nucleus来抑制疼痛信息的传导。除此还有个疼痛是常见的现象，就是全身肌肉的强直，即通过强化external globus pallidus的放电来抑制subthalamic nucleus，避免internal globus pallidus同时接收抑制型递质和兴奋型递质，但是此时external globus pallidus也会强烈输出抑制到thalamic reticular formation，从而使后者放松对丘脑的抑制。要是遇到疼痛时选择去抑制putamen，来避免internal globus pallidus同时接收抑制型递质和兴奋型递质，也应该是一种常见处理方案。)

, and from the pars parafascicularis of the central complex

（或许，这是被动受击时产生的强直。换句话说，疼痛信息可以通过STN来减少个体的主动行为，不影响被动行为，但是可以通过reticulata来影响眼动。如果疼痛信息能够到达putamen，那么就可以影响主动行为，事实上一部分疼痛信息是可以到达中脑的多巴胺系统核团，从而影响主动行为，但是还有一部分来自内脏的疼痛信息显然是可以强烈抑制主动行为。在我看来，STN的功能是非常明确的。）

. The subthalamic nucleus also receives neuromodulatory inputs, notably dopaminergic axons from the substantia nigra pars compacta.

（这就有意思了，subthalamic nucleus投射到reticulata从而抑制compacta，然后compacta还投射到subthalamic nucleus，来兴奋之，是为了避免compacta持续兴奋吗，从而达到compacta周期性兴奋的效果？）

[7] It also receives inputs from the pedunculopontine nucleus

(但是，据其他wiki词条，pedunculopontine nucleus也投射兴奋axon到STN。).

Efferent targets[edit]

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（比如reticulata、internal globus pallidus，）.[8] 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.[8][9] When all axons reaching this target are added, the main efference of the subthalamic nucleus is, in 82.7% of the cases, clearly the internal globus pallidus (GPi).（在这前面的话是不是没有没有用？）

Some researchers have reported internal axon collaterals.[10] However, there is little functional evidence for this.

Physiology[edit]

 

Anatomical overview of the main circuits of the basal ganglia. Subthalamic nucleus is shown in red. Picture shows 2 coronal slices that have been superimposed to include the involved basal ganglia structures. + and - signs at the point of the arrows indicate respectively whether the pathway is excitatory or inhibitory in effect. Green arrows refer to excitatory glutamatergic pathways, red arrowsrefer to inhibitory GABAergic pathways and turquoise arrows refer to dopaminergic pathways that are excitatory on the direct pathway and inhibitory on the indirect pathway.

Subthalamic nucleus[edit]

The first intracellular electrical recordings of subthalamic neurons were performed using sharp electrodes in a rat slice preparation.[citation needed] 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",[11] since they can generate spontaneous action potentials at rates of 80 to 90 Hz in primates

（这个或许是人类、大猩猩、黑猩猩、红毛猩猩在通常情况下活动频率慢的原因吧，STN能够在顶叶视觉信息的作用下去抑制主动行为，从而保证个体有较多的时间去观察和思考。）.

Oscillatory and synchronous activity[12][13] is likely to be a typical pattern of discharge in subthalamic neurons recorded from patients and animal models characterized by the loss of dopaminergic cells in the substantia nigra pars compacta, which is the principal pathology that underlies Parkinson's disease.

Lateropallido-subthalamic system[edit]

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"[14] with synchronous bursts.

（最初的语言应该是先建立声音与顶叶视觉信息的联系，完成发生与视觉信息的记忆（注意，对英语而言，是建立元音与顶叶视觉信息的联系），然后在此基础上才能做到连续不断地发声，建立颞叶的视觉信息与连续声音之间的联系（注意，这里指的是多音节与颞叶视觉信息的联系），前者处于NE状态，后者处于DA状态；然后对于多音节发音的结束用顶叶的视觉信息来兴奋STN从而截止发音，这建立了多音节声音与顶叶视觉信息的记忆联系，在这个多音节的过程中，用到了颞叶信息，并且还把顶叶视觉信息给拉进来，实现了颞叶视觉信息-声音-顶叶视觉信息三者的共同活动。差不多，这应该就是口语（不包含认字）的工作机制吧，这个可以从2、3岁孩子掌握语言的过程中观察到。）

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.[15] 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.[16] The activity of the medial pallidum is influenced by afferences from the lateral pallidum and from the subthalamic nucleus.[17] The same for the substantia nigra pars reticulata.[9] The subthalamic nucleus sends axons to another regulator: the pedunculo-pontine complex （应该是pedunculopontine nucleus。）(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.[18]

Pathophysiology[edit]

Chronic stimulation of the STN, called deep brain stimulation (DBS), is used to treat patients with Parkinson disease. The first to be stimulated are the terminal arborisations of afferent axons, which modify the activity of subthalamic neurons. However, it has been shown in thalamic slices from mice,[19] 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.

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.

As one of the STN's suspected functions is in impulse control

(突然停止行为（比如投掷行为）中停止的那部分控制，而一侧STN的损伤导致停止部分控制丧失，导致投掷行为得不到突然停止（比如紧握球的手没有及时松手），类似的，从而增加了动作发生的时间。)

, dysfunction in this region has been implicated in obsessive–compulsive disorder.[20] Artificially stimulating the STN has shown some promise in correcting severe impulsive behavior

（难道STN损伤的人更容易冲动？）

 and may later be used as an alternative treatment for the disorder.[21]

Function[edit]

The function of the STN is unknown, but current theories place it as a component of the basal ganglia control system that may perform action selection. It is thought to implement the so-called "hyperdirect pathway" of motor control, contrasting with the direct and indirect pathways implemented elsewhere in the basal ganglia. STN dysfunction has also been shown to increase impulsivity in individuals presented with two equally rewarding stimuli.[22]

Research has suggested that the subthalamus is an extrapyramidal center. It holds muscular responses in check, and damage may result in hemiballism (a violent flinging of the arm and leg on one side of the body).[23]