The Indirect Pathway
The indirect pathway begins with the Striatum being excited by the Cortex (just like the direct pathway). Then Striatal neurons send inhibitory input to the external segment of the Globus Pallidus using the neurotransmitters GABA or Enkephalin (enk). The Globus Pallidus external segment usually sends inhibitory input to the Subthalamic Nucleus using GABA, but if it is inhibited by the Striatum then it is unable to inhibit the Subthalamic nucleus leaving it free to fire. The Subthalamic Nucleus being uninhibited sends the only purely excitatory input within the Basal Ganglia pathways to the Globus Pallidus internal segment and the Substantia Nigra pars reticulata. These structures then inhibit the VA and VL of the Thalamus making it unable to send excitatory input to the Cortex and thus indirectly inhibiting the Motor Cortices, which inhibits movement.
The Substantia Nigra pars compacta
The Substantia Nigra pars compact plays a key role in the balance of direct versus indirect pathway. If functioning correctly the Substantia Nigra pars compacta has the overall effect of facilitating intended movement and inhibiting unintended movement. It does this by exciting the direct pathway and inhibiting the indirect pathway through release of the neurotransmitter Dopamine. Striatal neurons of the direct pathway have D1 receptors which are excited by Dopamine, whereas Striatal neurons of the indirect pathway have D2 receptors which are inhibited by Dopamine. The Substantia Nigra pars compacta also sends excitatory input directly to the Cortex again using Dopamine.
Cholinergic (ACh) Striatal Interneurons
There are also cholinergic interneurons located within the Striatum that synapse on both the neurons of the direct and indirect pathways. These interneurons have the opposite affect of dopamine. Release of ACh causes the Striatal neurons of the direct pathway to be inhibited and the Striatal neurons of the indirect pathway to be excited. Thus these cholinergic interneurons add to the balance of control between the direct and indirect pathways.
Note:
(In all cases of excitation and inhibition we must remember that there are individual neurons being depolarized or hyperpolarized by excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs) respectively, via chemically gated ion channels involving spatial and temporal summation. If a greater number of neurons reach threshold and then depolarize firing an action potential than do not then you will most likely see excitation of neurons in the next structure. We must also remember that whether a neuron is excited or inhibited by a chemically gated ion channel depends upon the neurotransmitters in the synaptic cleft and most importantly upon the receptors of the postsynaptic neuron.)
Parkinson's Disease
Parkinson's disease is a hypokinetic disorder that is the result of Basal Ganglia dysfunction. Patients with Parkinson's disease exhibit several key signs of motor dysfunction, these being difficulty initiating movement, bradykinesia, shuffling gait, flexed posture, impaired balance, muscular rigidity, and tremor. The disease usually develops later in life (typically in people 55 years or older) and as it progresses can lead to depression, anxiety, and eventually memory loss or dementia. The exact causes of Basal Ganglia dysfunction that results in Parkinson's disease are not well know but some possible effectors could be environmental, genetic, or brain injury. There are a few treatments for Parkinson's but no known cures. These treatments usually involve dopamine supplementation or imitation, or reducing the amount of Acetylcholine (ACh) in the striatum as well as surgical lesioning of the Subthalamic Nucleus or Globus Pallidus internus (both components of the Basal Ganglia).
The reasoning behind these treatments is because Parkinson's is a result of a disruption between the balance of the direct versus the indirect pathway. This balance is tipped more towards the indirect pathway resulting in less facilitation and more inhibition of movement. This disruption is caused by lesions of the Substantia Nigra pars compacta. This death of neurons in the pars compacta means that they can no longer release dopamine and excite the Striatal neurons in the direct pathway and inhibit the Striatal neurons in the indirect pathway. The pars compact also can no longer excite the Cortex directly.
Now due to the over-activity of the indirect pathway we see the signs of Parkinson's disease being exhibited. We understand why these are the symptoms because we know how the pathways within the Basal Ganglia function. All of the symptoms reflect the increase in inhibition of movement and the decrease in facilitation.
Treatments of Parkinson's involving supplementation or imitation of Dopamine or lowering of Acetylcholine levels, as well as surgically lesioning the Subthalamic Nucleus or the internal segment of the Globus Pallidus aim to corre
ทางเดินอ้อมทางเดินอ้อมเริ่มต้น ด้วย Striatum ที่กำลังตื่นเต้น โดยคอร์เทกซ์ (เหมือนทางเดินตรง) แล้ว Striatal neurons ส่งลิปกลอสไขเข้าส่วนภายนอกของ Pallidus เทิร์นโกลบัสใช้ neurotransmitters สารกาบาหรือ Enkephalin (enk) เซ็กเมนต์ Pallidus เทิร์นโกลบัสภายนอกมักจะส่งเข้านิวเคลียส Subthalamic ลิปกลอสไขใช้สารกาบา แต่ถ้ามันถูกห้าม โดย Striatum แล้วไม่สามารถยับยั้งนิวเคลียส Subthalamic ที่ปล่อยฟรีไฟ เป็นนิวเคลียส Subthalamic ยิ่งส่งอินพุต excitatory เพียงอย่างเดียวเท่านั้นภายในมนต์ Ganglia มะเร็งไป Pallidus เทิร์นโกลบัสภายในเซ็กเมนต์และ reticulata พารอินเต Substantia Nigra โครงสร้างเหล่านี้แล้วยับยั้ง VA และ VL ทาลามัสทำให้ไม่สามารถส่งเข้าคอร์เทกซ์ excitatory และดัง inhibiting Cortices มอเตอร์ อ้อมซึ่งยับยั้งการเคลื่อนไหวCompacta พารอินเต Substantia Nigraคอมแพคพารอินเต Substantia Nigra มีบทบาทสำคัญในยอดดุลของโดยตรงกับทางเดินอ้อม ถ้าทำงาน compacta พารอินเต Substantia Nigra มีผลโดยรวมของการอำนวยความสะดวกไว้เคลื่อนไหวและ inhibiting ตั้งใจเคลื่อนไหว มันสามารถทำได้ โดยทางเดินตรงที่น่าตื่นเต้น และ inhibiting ทางเดินอ้อมผ่านของสารสื่อประสาทโดปามีน Striatal neurons ของทางเดินโดยตรงมีง 1 receptors ซึ่งตื่นเต้น โดยโดพามีน ขณะ Striatal neurons ของทางเดินทางอ้อมได้ D2 receptors ซึ่งห้าม โดยโดพามีน Compacta พารอินเต Substantia Nigra ยังส่ง excitatory เข้าตรงไปคอร์เทกซ์ใช้โดพามีนอีกInterneurons Striatal cholinergic (ACh)นอกจากนี้ยังมี interneurons cholinergic Striatum ที่พักที่ไซแนปส์กับ neurons ทั้งของมนต์ทางตรง และทางอ้อม Interneurons เหล่านี้มีผลตรงกันข้ามของโดปามีน ปล่อยของ ACh ทำ neurons Striatal ของทางเดินตรงไปจะห้ามและ neurons Striatal ของทางเดินอ้อมจะตื่นเต้น ดัง นี้ interneurons cholinergic เพิ่มในยอดดุลการควบคุมระหว่างทางเดินทางตรง และทางอ้อมหมายเหตุ:(In all cases of excitation and inhibition we must remember that there are individual neurons being depolarized or hyperpolarized by excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs) respectively, via chemically gated ion channels involving spatial and temporal summation. If a greater number of neurons reach threshold and then depolarize firing an action potential than do not then you will most likely see excitation of neurons in the next structure. We must also remember that whether a neuron is excited or inhibited by a chemically gated ion channel depends upon the neurotransmitters in the synaptic cleft and most importantly upon the receptors of the postsynaptic neuron.)Parkinson's DiseaseParkinson's disease is a hypokinetic disorder that is the result of Basal Ganglia dysfunction. Patients with Parkinson's disease exhibit several key signs of motor dysfunction, these being difficulty initiating movement, bradykinesia, shuffling gait, flexed posture, impaired balance, muscular rigidity, and tremor. The disease usually develops later in life (typically in people 55 years or older) and as it progresses can lead to depression, anxiety, and eventually memory loss or dementia. The exact causes of Basal Ganglia dysfunction that results in Parkinson's disease are not well know but some possible effectors could be environmental, genetic, or brain injury. There are a few treatments for Parkinson's but no known cures. These treatments usually involve dopamine supplementation or imitation, or reducing the amount of Acetylcholine (ACh) in the striatum as well as surgical lesioning of the Subthalamic Nucleus or Globus Pallidus internus (both components of the Basal Ganglia).The reasoning behind these treatments is because Parkinson's is a result of a disruption between the balance of the direct versus the indirect pathway. This balance is tipped more towards the indirect pathway resulting in less facilitation and more inhibition of movement. This disruption is caused by lesions of the Substantia Nigra pars compacta. This death of neurons in the pars compacta means that they can no longer release dopamine and excite the Striatal neurons in the direct pathway and inhibit the Striatal neurons in the indirect pathway. The pars compact also can no longer excite the Cortex directly.
Now due to the over-activity of the indirect pathway we see the signs of Parkinson's disease being exhibited. We understand why these are the symptoms because we know how the pathways within the Basal Ganglia function. All of the symptoms reflect the increase in inhibition of movement and the decrease in facilitation.
Treatments of Parkinson's involving supplementation or imitation of Dopamine or lowering of Acetylcholine levels, as well as surgically lesioning the Subthalamic Nucleus or the internal segment of the Globus Pallidus aim to corre
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