神經解剖學 NEUROANATOMY BASAL NUCLEI 盧家鋒助理教授臺北醫學大學醫學系解剖學暨細胞生物學科臺北醫學大學醫學院轉譯影像研究中心 http://www.ym.edu.tw/~cflu
OUTLINE Components and Pathways of the Basal Nuclei Functions and Related Disorders of the Basal Nuclei Fundamental Neuroscience (4th edition) Chapter 26: The Basal Nuclei Atlas of the Human Brain (3rd edition) http://www.ym.edu.tw/~cflu 2017/11/20 2
COMPONENTS AND PATHWAYS OF THE BASAL NUCLEI http://www.ym.edu.tw/~cflu 2017/11/20 3
BASAL NUCLEI Dorsal basal nuclei: the caudate and lenticular nuclei Ventral striatum: the nucleus accumbens plus parts of the adjacent olfactory tubercle Ventral pallidum: the substantia innominata http://www.ym.edu.tw/~cflu 2017/11/20 4
BASAL NUCLEI Caudate nucleus Putamen Basal nuclei Globus pallidus External Internal Subthalamic nucleus Substantia nigra Thalamus Caudolenticular Gray bridge Caudate nucleus (body) Caudate nucleus (head) Amygdala Putamen Caudate nucleus Globus pallidus: External segment Internal segment Lateral view Putamen Caudate nucleus (tail) Subthalamic nucleus Substantia nigra http://www.ym.edu.tw/~cflu Nucleus accumbens 2017/11/20 5 Amygdala Medial view
BLOOD SUPPLY Through anterior Perforated substance Frontal operculum Temporal operculum (ACA) (MCA) (PCA) (PCA) http://www.ym.edu.tw/~cflu 2017/11/20 6 (PCA) (ICA/MCA)
STRIATAL COMPLEX Striatal complex Caudate nucleus Putamen Nucleus accumbens Olfactory tubercle http://www.ym.edu.tw/~cflu 2017/11/20 7
STRIATAL COMPLEX Medium spiny neuron (MSN) Medium sized cell bodies Large numbers of spines on the dendrites GABAergic neuron GABA: γ aminobutyric acid (GABA), an inhibitory neurotransmitter http://www.ym.edu.tw/~cflu 2017/11/20 8
STRIATAL COMPLEX Striosomes (Patches) of striatal complex Most prominent in the head of the caudate. Acetylcholinesterase poor regions Striosomes are surrounded by matrix Matrix contains high concentrations of acetylcholine. http://www.ym.edu.tw/~cflu 2017/11/20 9
CONNECTIONS OF STRIATAL COMPLEX Afferent projections Cerebral cortex corticostriatal fibers putamen (Major afferent) Thalamus thalamostriatal fibers putamen Substantia nigra nigrostriatal fibers putamen Parabrachial pontine reticular formation pedunculopontostriatal fibers putamen http://www.ym.edu.tw/~cflu 2017/11/20 10
CONNECTIONS OF STRIATAL COMPLEX Efferent projections Putamen striatopallidal fibers globus pallidus Putamen striatonigral fibers Substantia nigra http://www.ym.edu.tw/~cflu 2017/11/20 11
CONNECTIONS OF NUCLEUS ACCUMBENS http://www.ym.edu.tw/~cflu 2017/11/20 12
PALLIDAL COMPLEX Pallidal complex Globus pallidus Substantia innominata Contains primarily GABAergic neurons with high rates of spontaneous activity. These cells tonically inhibit their targets. Caudate nucleus Globus pallidus Internal (medial) segment External (lateral) segment Substantia innominata http://www.ym.edu.tw/~cflu 2017/11/20 13
CONNECTIONS OF GLOBUS PALLIDUS Interconnections between internal and external segments Pallidopallidal fibers Afferent projections Striatal complex striatopallidal fibers globus pallidus (Major afferent) Subthalamus nucleus subthalamopallidal fibers globus pallidus Substantia nigra, pars compacta nigropallidal fibers globus pallidus http://www.ym.edu.tw/~cflu 2017/11/20 14
CONNECTIONS OF GLOBUS PALLIDUS Efferent projections Internal segment of globus pallidus pallidothalamic fibers thalamus External segment of globus pallidus pallidosubthalamic fibers subthalamic nucleus External segment of globus pallidus pallidonigral fibers substantia nigra Pallidothalamic fibers Lenticular fasciculus Ansa lenticularis Thalamic fasciculus http://www.ym.edu.tw/~cflu 2017/11/20 15
SUBTHALAMUS NUCLEUS & NIGRAL COMPLEX Connections of Subthalamus (glutamate neurotransmitter) Connections of Substantia nigra (dopamine neurotransmitter) http://www.ym.edu.tw/~cflu 2017/11/20 16
DIRECT PATHWAYS The direct pathway facilitates a flow of information through the thalamus. Corticostriatal fibers (+), striatopallidal fibers ( ), pallidothalamic fibers ( ). Corticostriatal fibers (+), striatonigral fibers ( ), nigrathalamic fibers ( ). http://www.ym.edu.tw/~cflu 2017/11/20 17
DIRECT PATHWAYS Excitation http://www.ym.edu.tw/~cflu 2017/11/20 18
INDIRECT PATHWAYS The indirect pathway inhibits the flow of information through the thalamus. Corticostriatal fibers (+), striatopallidal fibers ( ), pallidosubthalamic fibers ( ), subthalamopallidal fibers (+), pallidothalamic fibers ( ) Corticosubthalamic fibers (+), subthalamopallidal fibers (+), pallidothalamic fibers ( ) http://www.ym.edu.tw/~cflu 2017/11/20 19
INDIRECT PATHWAYS 2017/11/20 http://www.ym.edu.tw/~cflu 20 Inhibition
BASAL NUCLEAR FUNCTION Thalamic disinhibition: The function of the direct pathway is to release the thalamus from its pallidal inhibition. Subthalamic disinhibition: In the indirect pathway, the subthalamic nucleus is released from inhibition by the lateral pallidal segment. BALANCE Direct pathway Indirect pathway http://www.ym.edu.tw/~cflu 2017/11/20 21
FUNCTIONS AND RELATED DISORDERS OF THE BASAL NUCLEI http://www.ym.edu.tw/~cflu 2017/11/20 22
PARALLEL CIRCUITS Each circuit is an independent channel that processes information from one functional type of cortex by way of its own areas of the basal nuclei and thalamus and returns to the appropriate functionally related part of cortex. Motor (sensorimotor) loop Executive (Associative) loop Motivational (limbic) loop Visuomotor (oculomotor) loop Cerebral cortex Basal nuclei Thalamus Visuomotor Corticostriatal Loops Motor Executive Motivational http://www.ym.edu.tw/~cflu 2017/11/20 23
MOTOR LOOP Motor control Cerebral cortex Supplementary motor, primary motor, premotor, and somatosensory cortices Basal nuclei Putamen (Put), internal segment of the globus pallidus (GPi) Thalamus Oral part and medial portion of ventrolateral nucleus Brainstem motor centers http://www.ym.edu.tw/~cflu 2017/11/20 24 Krack et al. Trends in neurosciences. 2010;33(10):474 84.
EXECUTIVE LOOP Cerebral cortex Dorsolateral prefrontal and posterior parietal cortices Basal nuclei Caudate nucleus (Cn), Putamen (Put), internal segment of the globus pallidus (GPi) Thalamus Multiple tasks, learning, selection Parvicellular region of ventroanterior nucleus Parvicellular region of dorsomedial nucleus Brainstem motor centers http://www.ym.edu.tw/~cflu 2017/11/20 25 Krack et al. Trends in neurosciences. 2010;33(10):474 84.
MOTIVATIONAL LOOP Cerebral cortex Lateral orbitofrontal, anterior cingulate, medial prefrontal cortices, amygdala, and hippocampus Basal nuclei Caudate nucleus (Cn), Putamen (Put), internal segment of the globus pallidus (GPi), and nucleus accumbens Thalamus Wanting and emotion Magnocellular portion of ventroanterior nucleus Magnocellular and posteriomedial portions of dorsomedial nucleus http://www.ym.edu.tw/~cflu 2017/11/20 26 Krack et al. Trends in neurosciences. 2010;33(10):474 84.
VISUOMOTOR LOOP Visual functions and eye movements Cerebral cortex Frontal eye fields and visual portions of the temporal cortex Basal nuclei Caudate nucleus (Cn), Putamen (Put), internal segment of the globus pallidus (GPi) Thalamus Magnocellular portion of ventroanterior nucleus Parvicellular region of dorsomedial nucleus Superior colliculus in midbrain http://www.ym.edu.tw/~cflu 2017/11/20 27
INTEGRATED FUNCTION OF BASAL NUCLEI The activity in the cerebral cortex activates the striatopallidal neurons in both the direct and indirect pathways. Careful balance of the activity between the two pathways modulates the amount of time which the thalamocortical neurons are activated. The modulation between the direct and indirect pathways is controlled by dopaminergic loop (neostriatum substantia nigra) DOPAMINE (+/ ) GLUTAMATE (+) GABA ( ) http://www.ym.edu.tw/~cflu 2017/11/20 28
INTEGRATED FUNCTION OF BASAL NUCLEI http://www.ym.edu.tw/~cflu 2017/11/20 29
LOSS OF DOPAMINERGIC NIGRAL CONNECTIONS http://www.ym.edu.tw/~cflu 2017/11/20 30
DOPAMINERGIC LOOP Direct pathway uses D1 receptors excitation of the striatopallidal neurons. Indirect pathway uses D2 receptors inhibition of the striatopallidal neurons. http://www.ym.edu.tw/~cflu 2017/11/20 31
RELATED DISORDERS HUNTINGTON DISEASE A genetic disorder (short arm of chromosome 4) that generally begins to appear at 35 to 44 years of age; death occurs 10 to 15 years after onset. Early stage Middle stage Late stage Clumsiness Involuntary twitching Lacking coordination Depression Irritability Choreiform Memory loss, forgetfulness Slurred speech Swallowing difficulty Dependent on others High risks for choking, falling and heart failure. http://www.ym.edu.tw/~cflu 2017/11/20 32
RELATED DISORDERS HUNTINGTON DISEASE Decrease in the size of the striatal complex caused by loss of about 90% of all striatal neurons. http://www.ym.edu.tw/~cflu http://depts.washington.edu/cibr 2017/11/20 33
RELATED DISORDERS PARKINSON DISEASE Most adult patients with Parkinson disease appear initially symptoms in the age range of 45 to 65 years. This disorder is characterized by a progressive onset of movement and affective disturbances. Akinesia (difficulty initiating a movement) Resting tremor http://www.ym.edu.tw/~cflu 2017/11/20 34
RELATED DISORDERS PARKINSON DISEASE Clinical symptoms usually appear after approximately 70% to 80% of nigral neurons and their corresponding dopamine are lost. Healthy individual Parkinson s disease Swallow tail sign Substantia nigra: the dopamine producing region Schwarz et al. PLoS ONE. 2014;9 (4): e93814. http://www.ym.edu.tw/~cflu 35
RELATED DISORDERS WILSON DISEASE A genetic disorder (long arm of chromosome 13); typically onset between 11 and 25 years of age. A disorder of copper metabolism accumulation of the metal in the liver and damage to various areas of the brain; Also known as hepatolenticular degeneration. Kayser Fleischer ring (in 75% patients) After copper chelating treatment http://www.ym.edu.tw/~cflu Schrag et al. NEJM 2012;366(12):e18. 2017/11/20 36
RELATED DISORDERS WILSON DISEASE Symptoms and MRI features (loss of neurons, axonal degeneration, and increasing numbers of protoplasmic astrocytes). Patient with WD After 3 year treatment Kim et al. AJNR 2006;27(6):1373 8. 37 https://www.thinglink.com/scene/751801798536200194
12/4 教學評量 16:50, 請同學務必到課 THE END ALVIN4016@TMU.EDU.TW (TMU EXT. 3273) http://www.ym.edu.tw/~cflu 2017/11/20 38