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Physiology of the Basal Ganglia
and Cerebellum
Thomas C. Westfall
Important Things to Know About Striatal Outputs
• What happens when we excite the outputs from the
striatum via the direct and indirect pathways
• What happens when we increase the neuronal firing
of dopamine neurons (the nigral-striatal pathway)
• What happens in Parkinson’s Disease when we
decrease dopamine activity
Cotransmitters Involved in Striatal Output
DIRECT PATHWAY:
Striatum to Globus Pallidus pars interna (GPi)/Substantia Nigra pars
reticulata (SNpr)
•GABA
•Substance P
•Dynorphin
INDIRECT PATHWAY:
Striatum to Globus Pallidus pars externa (GPe)
•GABA
•Enkephalin
FEEDBACK LOOP
Striatum to Substantia Nigra pars compacta (SNpc)
•GABA
•Substance P
•(Neurotensin)
•Dynorphin
Principle Amino Acid Transmitters in the Mammalian
Central Nervous System
Excitatory Amino Acids
•Glutamate (Glu)
•Aspartate (ASP)
These depolarize neurons in the mammalian CNS
Inhibitory Amino Acids
•γ-aminobutyric acid (GABA)
•Glycine (Gly)
•Taurine
•β-alanine
These hyperpolarize neurons in the mammalian CNS
Classification of Ionotropic Glutamate Receptor Subtypes
IONOTROPIC
GLUTAMATE
RECEPTOR SUBTYPE
Subunits
Agonists
Actions
AMPA
gluR1
GluR2
GluR3
GluR4
Glutamate or AMPA
Increase Na+ and Ca2+
influx, increase K+ efflux
(N.B. receptors with
GluR2 have ion channels
with decreased Ca2+
permeability)
Kainate
GluR5
GluR6
GluR7
KA1
KA2
Glutamate or kainate
Increase K+ efflux
NMDA
NR1
NR2A
NR2B
NR2C
NR2D
Glutamate or NMDA and
glycine and membrane
depolarization
Increase Ca2+ influx,
increase K+ efflux
Metabotropic Glutamate Receptor (mGluR) Subtypes and Their Actions
Group
Subtype
Actions
I
mGluR1
MGluR5
Activated adenylyl cyclase → increases cAMP (mGluR1
only)
Increases PLC activity → PIP2 hydrolysis → increases
IP3 and DAG → increases Ca2+ levels, stimulates PKC
Inhibits K+ channels
II
MGluR2
mGluR3
Inhibits adenylyl cyclase → decreases cAMP
Inhibits voltage-sensitive Ca2+ channels
Activates K+ channels
III
mGluR4
mGluR6
mGluR7
mGluR8
Inhibits adenyly cyclase → decreases cAMP
Inhibits voltage-sensitive Ca2+ channels
Group I mGluRs activate adenylyl cyclase and phospholipase C(PLC), while group II and group III mGluRs inhibit
adenylyl cyclase. The downstream effects of mGluRs on ion channels and complex and varied. Some of the main
actions on ion channels are listed. Note that the actions of group I receptors are generally excitatory, while those of
groups II and III receptors are generally inhibitory.
Function of the Basal Ganglia
• Motor Function
• Gating Function
• Cognitive Function
• Emotion and Motivational Behavior
Projection Targets
Fiber Type or
Neuron
Deep
Nuclei
Purkinje Basket
Climbing
+
+
Mossy
+
?
Stellate
Granule
?
+
Golgi Action
Neurotransmitter
?
Excit.
Aspartate
+
Excit.
Acetylcholine
Cerebellar Neurons
Neuron
Type
Layer
Projection
Action
Neurotransmitter
Purkinje
Principal
(projection)
Purkinje
Deep cerebellar nuclei
Lateral vestibular nucleus
Intrinsic neurons
Inhib.
GABA
Basket
Interneuron
Molecular
Purkinje cell
Inhib.
GABA
Stellate
Interneuron
Molecular
Purkinje cell
Inhib.
GABA
Granule
Interneuron
Granule
Purkinje cell
Basket Cell
Stellate Cell
Golgi Cell
Excit.
Glutamate
Golgi
Interneuron
Granule
Granule Cell
Inhib.
GABA
Similarities Between the Basal Ganglia and
Cerebellum
• Components of the Motor System
• Influence cerebral cortical activity via the Thalamus
• Linked with the Cerebral Cortex via recurrent loops
• Have internal (local) circuitry that modulates loop activity
• Receive modulating inputs that influence their activity
Eg:
¾Climbing fibers in cerebellum
¾Dopamine inputs in basal ganglia