山东大学医学院：治疗帕金森病的药物 Motor systems II：The basal ganglia and Drugs used for the treatment of Parkinson’s disease

1901 Motor systems The basal ganglia and Drugs used for the treatment of parkinson's disease Zhang Bin(张斌) Institute of Pharmacology School of medicine Shandong University

1 Motor systems II: The basal ganglia and Drugs used for the treatment of Parkinson’s disease Zhang Bin（张斌） Institute of Pharmacology School of Medicine Shandong University

Spinal cord Muscle Motor cortex Th alamos Other neuro transmitters GABA Acetylcholine Globus When dopamine-producing Pallidus die. loss of dopamine release in the Pars compacta striatum causes the acetylcholine producers there to overstimulate their target Dopamine neurons, thereby triggering a chain reaction of abnormal Striatum signaling leading to impaired Substantia nigra mobility Parkinson's disease

1. Components of Basal Ganglia VL nucleus of Caudate nucleus neostriatum striatum pallidus(paleostriatum) Subthalamic Substantia nigra

1. Components of Basal Ganglia 3 neostriatum striatum (paleostriatum)

1. Caudate nucleus(尾状核) 2 Putamen(壳核豆状核壳) 新纹状体 3. Globus pallidus(GP)(苍白球,旧纹状体) 4. Substantia Nigra(SN)(黑质 Pars compacta(p.c)(致密部) Pars reticulata(pr)(网状部) 5. Subthalamic nucleus(STN)(丘脑底核) cortex caudate &x putamen globus ext. pallidus thalamus subthalamic nucleus substantia nigra 新纹状体是基底节的核心,许多神经传入进来,也会 发出神经纤维到其他部位,构成回路调控躯体运动

• 1. Caudate Nucleus (尾状核） • 2. Putamen (壳核,豆状核壳） • 3.Globus Pallidus (GP) （苍白球，旧纹状体） • 4. Substantia Nigra (SN)（黑质） Pars Compacta (p.c.) (致密部） Pars Reticulata (p.r.) （网状部） • 5. Subthalamic Nucleus (STN) (丘脑底核） 4 新纹状体 新纹状体是基底节的核心，许多神经传入进来，也会 发出神经纤维到其他部位，构成回路调控躯体运动

2. Medium spiny neuron in striatum (MSN中型多棘神经元) D) MSN is the main efferent neurons in neostriatum 2)MSN( Dendrites)接受的 afferent神经: Glu neurons in cortex c)multipolar axon soma DA neurons in snc endnotes Ach neurons in striatum GABA neurons in striatum 3)MSN axons compose efferent system, with GABa as the neurotransmitter

2. Medium spiny neuron in striatum (MSN,中型多棘神经元) 1) MSN is the main efferent neurons in neostriatum 2) MSN（ Dendrites）接受的afferent神经: Glu neurons in cortex DA neurons in SNc Ach neurons in striatum GABA neurons in striatum 3) MSN axons compose efferent system, with GABA as the neurotransmitter 5

4)Two types of da receptors on MSN: D, and D2-R D1-R: enhance direct pathway→Gipi(苍白球内侧部) D2R: inhibit indirect pathway→GPe(苍白球外侧部

4) Two types of DA receptors on MSN: D1 and D2 -R D1 -R : enhance direct pathway → Gpi (苍白球内侧部) D2 -R : inhibit indirect pathway → GPe (苍白球外侧部) 6

3. Circuit related with Basal ganglia's function in control of movement Cortex Cortex“ Cortex Glutamate Glutamate Glutamate Glutamate Glutamate GABA GABA GABA GABA GABAGABA SP and SP and SP and ENK DYN ENK DYN ENK Thalamus Thalamus Thalamus Dopamine opamine Dopamine GABA GABA GABA GABA GABA No GABA = GPvGABA GPVGABA GABA SNr GABA Glutamate GABA Glutamate GABA Glutamate STN Fig. 10. 1 Functional organization of the basal ganglia. The diagrams illustrate the functional organization of the basal ganglia circuits (A)under normal conditions; ( B)in Parkinsons disease; and (C)in Huntingtons disease. Broken lines indicate pathways that are hypoactive, and thick lines indicate pathways that are hyperactive DYN, dynorphins; ENK, enkephalins; GABA, -aminobutyric acid; GPe, external globus pallidum; GPi, internal globus pallidum: SNc, substantia nigra compacta; SNr, substantia nigra reticulata: SP, substance P: STN, subthalamic nucleus

7 3. Circuit related with Basal ganglia’s function in control of movement

1) direct pathway(直接通路:当新纹状体活动↑→皮层运 动前区活动↑ 2) indirect pathway(间接通路):当新纹状体活动个→皮层运 动前区活动。此通路部分抵消直接通路对皮层的兴奋作用 3) Substantia nigra- Neostriatum pathway黑质新纹状 体通路):此通路对上述两通路起调控作用 DA通过D受体增强直接通路,通过D2受体抑制间接通路

8 1) direct pathway (直接通路): 当新纹状体活动↑→皮层运 动前区活动↑ 2) indirect pathway (间接通路): 当新纹状体活动↑→皮层运 动前区活动↓。此通路部分抵消直接通路对皮层的兴奋作用 3) Substantia nigra-Neostriatum pathway(黑质-新 纹状 体通路): 此通路对上述两通路起调控作用 DA通过D1受体增强直接通路，通过D2受体抑制间接通路

4. Diseases related with dysfunction of basal ganglia Huntingtons disease( chorea) >运动过多,肌张力降低 a Parkinson disease >运动减少,肌张力增高

9 4. Diseases related with dysfunction of Basal ganglia ▪ Huntington’s disease (Chorea) ➢运动过多，肌张力降低 ▪ Parkinson disease ➢运动减少，肌张力增高

Cortical oscillatory inputs Glutamatergic Direct neurons from pathway afferents Cholinergic to GPe interneuron GPL SNr GLUL GABA ACh Striatonigral medium spiny Striatopallidal neuron medium spiny neuron GA A Indirect DA Dopaminergic pathway neurons from to GPe SN 10

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