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Basal Ganglia NBIO 401 – Friday November 1, 2013 Objectives: -Be able to describe the anatomical components of the basal ganglia and their position in the brain relative to the cerebral cortex, internal capsule, and thalamus. -Be able to describe how the components of the basal ganglia are connected to the cerebral cortex and to each other. -Be able to explain the general effects of the direct and indirect pathways through the basal ganglia on movement. -Be able to describe the effect of the substantia pars compacta on the direct and indirect pathways. -Be able to explain how, in addition to the pathways affecting limb movements, there are other loops between the basal ganglia and cerebral cortex that perform analogous functions for oculomotor, executive, and emotional systems. - Be able to describe the type of learning in which the basal ganglia are involved. Objectives: -Be able to describe the anatomical components of the basal ganglia and their position in the brain relative to the cerebral cortex, internal capsule, and thalamus. -Be able to describe how the components of the basal ganglia are connected to the cerebral cortex and to each other. -Be able to explain the general effects of the direct and indirect pathways through the basal ganglia on movement. -Be able to describe the effect of the substantia pars compacta on the direct and indirect pathways. -Be able to explain how, in addition to the pathways affecting limb movements, there are other loops between the basal ganglia and cerebral cortex that perform analogous functions for oculomotor, executive, and emotional systems. - Be able to describe the type of learning in which the basal ganglia are involved. Objectives: -Be able to describe the anatomical components of the basal ganglia and their position in the brain relative to the cerebral cortex, internal capsule, and thalamus. -Be able to describe how the components of the basal ganglia are connected to the cerebral cortex and to each other. -Be able to explain the general effects of the direct and indirect pathways through the basal ganglia on movement. -Be able to describe the effect of the substantia pars compacta on the direct and indirect pathways. -Be able to explain how, in addition to the pathways affecting limb movements, there are other loops between the basal ganglia and cerebral cortex that perform analogous functions for oculomotor, executive, and emotional systems. - Be able to describe the type of learning in which the basal ganglia are involved. Objectives: -Be able to describe the anatomical components of the basal ganglia and their position in the brain relative to the cerebral cortex, internal capsule, and thalamus. -Be able to describe how the components of the basal ganglia are connected to the cerebral cortex and to each other. -Be able to explain the general effects of the direct and indirect pathways through the basal ganglia on movement. -Be able to describe the effect of the substantia pars compacta on the direct and indirect pathways. -Be able to explain how, in addition to the pathways affecting limb movements, there are other loops between the basal ganglia and cerebral cortex that perform analogous functions for oculomotor, executive, and emotional systems. - Be able to describe the type of learning in which the basal ganglia are involved. Objectives: -Be able to describe the anatomical components of the basal ganglia and their position in the brain relative to the cerebral cortex, internal capsule, and thalamus. -Be able to describe how the components of the basal ganglia are connected to the cerebral cortex and to each other. -Be able to explain the general effects of the direct and indirect pathways through the basal ganglia on movement. -Be able to describe the effect of the substantia pars compacta on the direct and indirect pathways. -Be able to explain how, in addition to the pathways affecting limb movements, there are other loops between the basal ganglia and cerebral cortex that perform analogous functions for oculomotor, executive, and emotional systems. - Be able to describe the type of learning in which the basal ganglia are involved. Objectives: -Be able to describe the anatomical components of the basal ganglia and their position in the brain relative to the cerebral cortex, internal capsule, and thalamus. -Be able to describe how the components of the basal ganglia are connected to the cerebral cortex and to each other. -Be able to explain the general effects of the direct and indirect pathways through the basal ganglia on movement. -Be able to describe the effect of the substantia pars compacta on the direct and indirect pathways. -Be able to explain how, in addition to the pathways affecting limb movements, there are other loops between the basal ganglia and cerebral cortex that perform analogous functions for oculomotor, executive, and emotional systems. - Be able to describe the type of learning in which the basal ganglia are involved. Basal Ganglia Position in the Brain Striatum = Caudate & Putamen Substantia Nigra Pars Reticulata (like GPi) Input Nuclei (caudate, putamen) Intermediate Nuclei (external globus pallidus, subthalamic nucleus) Output Nuclei (internal globus pallidus, substantia nigra pars reticulata) Pars Compacta (dopamine source) Basal Ganglia Functional Organization Functional organization of the Basal Ganglia Cortex Motor Cortex Subthalamic nucleus Globus pallidus Internal & substantia nigra pars reticulata Indirect Pathway Basal Ganglia Direct Pathway Globus pallidus external (decreases inhibition of thalamus) (increases inhibition of thalamus) Striatum Thalamus Excitatory Inhibitory Functional organization of the Basal Ganglia Cortex Motor Cortex Subthalamic nucleus Globus pallidus Internal & substantia nigra pars reticulata Indirect Pathway Basal Ganglia Direct Pathway Globus pallidus external (decreases inhibition of thalamus) (increases inhibition of thalamus) Striatum Thalamus Excitatory Inhibitory Functional organization of the Basal Ganglia Cortex Motor Cortex Subthalamic nucleus Globus pallidus Internal & substantia nigra pars reticulata Indirect Pathway Basal Ganglia Direct Pathway Globus pallidus external (decreases inhibition of thalamus) (increases inhibition of thalamus) Striatum Thalamus Excitatory Inhibitory Direct Pathway: Increases motor output Indirect Pathway: Decreases motor output Functional organization of the Basal Ganglia Cortex Motor Cortex Indirect Pathway Substantia nigra pars compacta Globus pallidus external Subthalamic nucleus Globus pallidus Internal & substantia nigra pars reticulata Basal Ganglia Direct Pathway (decreases inhibition of thalamus) (increases inhibition of thalamus) Striatum Thalamus Excitatory Inhibitory Direct Pathway: Increases motor output Indirect Pathway: Decreases motor output Functional organization of the Basal Ganglia Cortex Motor Cortex Indirect Pathway Substantia nigra pars compacta Globus pallidus external Subthalamic nucleus Globus pallidus Internal & substantia nigra pars reticulata Basal Ganglia Direct Pathway (decreases inhibition of thalamus) (increases inhibition of thalamus) Striatum Thalamus Excitatory Inhibitory Direct Pathway: Increases motor output Indirect Pathway: Decreases motor output Functional organization of the Basal Ganglia Cortex Motor Cortex Indirect Pathway Globus pallidus external Subthalamic nucleus D1 Globus pallidus Internal & substantia nigra pars reticulata Basal Ganglia Direct Pathway Substantia nigra pars compacta (decreases inhibition of thalamus) (increases inhibition of thalamus) Striatum Thalamus Excitatory Inhibitory Direct Pathway: Increases motor output Indirect Pathway: Decreases motor output Functional organization of the Basal Ganglia Cortex Motor Cortex Indirect Pathway Substantia nigra pars compacta Globus pallidus external Subthalamic nucleus D1 Globus pallidus Internal & substantia nigra pars reticulata Basal Ganglia Direct Pathway D2 (decreases inhibition of thalamus) (increases inhibition of thalamus) Striatum Thalamus Excitatory Inhibitory Direct Pathway: Increases motor output Indirect Pathway: Decreases motor output Functional organization of the Basal Ganglia Cortex Motor Cortex Indirect Pathway Substantia nigra pars compacta Globus pallidus external Subthalamic nucleus D1 Globus pallidus Internal & substantia nigra pars reticulata Basal Ganglia Direct Pathway D2 (decreases inhibition of thalamus) (increases inhibition of thalamus) Striatum Thalamus Excitatory Inhibitory Direct Pathway: Increases motor output Indirect Pathway: Decreases motor output Functional organization of the Basal Ganglia Cortex Motor Cortex Indirect Pathway Substantia nigra pars compacta Globus pallidus external Subthalamic nucleus D1 Globus pallidus Internal & substantia nigra pars reticulata Basal Ganglia Direct Pathway D2 (decreases inhibition of thalamus) (increases inhibition of thalamus) Striatum Thalamus Excitatory Inhibitory Direct Pathway: Increases motor output Indirect Pathway: Decreases motor output Functional organization of the Basal Ganglia Cortex Motor Cortex Indirect Pathway Substantia nigra pars compacta Globus pallidus external Subthalamic nucleus D1 Globus pallidus Internal & substantia nigra pars reticulata Basal Ganglia Direct Pathway D2 (decreases inhibition of thalamus) (increases inhibition of thalamus) Striatum Thalamus Excitatory Inhibitory Dopamine increases direct pathway activity Dopamine decreases indirect pathway activity Basal Ganglia Diseases Parkinson’s Disease Functional organization of the Basal Ganglia Cortex Motor Cortex Indirect Pathway X Substantia nigra pars compacta Globus pallidus external Subthalamic nucleus D1 Globus pallidus Internal & substantia nigra pars reticulata Basal Ganglia Direct Pathway D2 (decreases inhibition of thalamus) (increases inhibition of thalamus) Striatum Thalamus Excitatory Inhibitory Dopamine increases direct pathway activity Dopamine decreases indirect pathway activity Parkinson’s Disease Caused By SNc Damage Cortex dopamine dopamine Indirect Pathway Substantia nigra pars compacta Globus pallidus external Subthalamic nucleus D1 Globus pallidus Internal & substantia nigra pars reticulata Basal Ganglia Direct Pathway D2 (decreases inhibition of thalamus) (increases inhibition of thalamus) Striatum Motor Cortex Thalamus Excitatory Inhibitory Loss of dopamine decreases movement via both direct and indirect pathways. Parkinson’s disease Healthy / L-DOPA treatment Parkinson’s Disease Healthy / L-DOPA treatment Parkinson’s Disease Parkinson's Disease Gait Parkinson’s Disease Caused By SNc Damage Cortex dopamine dopamine Indirect Pathway Substantia nigra pars compacta Globus pallidus external Subthalamic nucleus D1 Globus pallidus Internal & substantia nigra pars reticulata Basal Ganglia Direct Pathway D2 (decreases inhibition of thalamus) (increases inhibition of thalamus) Striatum Motor Cortex Thalamus Excitatory Inhibitory Loss of dopamine decreases movement via both direct and indirect pathways. Pallidotomy Lehman et al, Acta Neurochir (2000) 142-319 Parkinson’s Disease Caused SNc Damage Cortex Motor Cortex Indirect Pathway Substantia nigra pars compacta Globus pallidus external Subthalamic nucleus D1 Globus pallidus Internal & substantia nigra pars reticulata Basal Ganglia Direct Pathway D2 (decreases inhibition of thalamus) (increases inhibition of thalamus) Striatum Thalamus Excitatory Inhibitory Loss of dopamine decreases movement via both direct and indirect pathways. Cortex Motor Cortex Striatum Basal Ganglia D2 Substantia nigra pars compacta Globus pallidus external Subthalamic nucleus D1 Thalamus Globus pallidus internal/ substantia nigra pars reticulata Huntington’s Disease Preferential degeneration of neurons in D2 expressing medium spiny neurons in the striatum that are the start of the indirect pathway. Huntington’s Disease Cortex Motor Cortex X Basal Ganglia D2 Striatum Substantia nigra pars compacta Globus pallidus external Subthalamic nucleus D1 Thalamus Globus pallidus internal/ substantia nigra pars reticulata Huntington’s Disease Preferential degeneration of indirect pathway Huntington’s disease Degeneration of MSNs in Striatum (Indirect pathway MSNs die first) Basal Ganglia Other Loops & Learning Striatum mediates associative learning (pairing one thing with another, stimulusresponse, reward, etc.) and procedural learning (motor patterns, development of habits and skills), but not spatial learning (absolute location, mental maps of space) which is mediated by the hippocampus (along with declarative memory). ende