Lecture 4 - Basal Ganglia Flashcards
What is the basal ganglia and where is it located?
-beneath the cerebral cortex and is a cluster of cell bodies within the CNS and is made up of interconnected structures
What makes up the striatum of the basal ganglia?
the caudate nucleus and the putamen
What is the striatum highly innervated by?
dopaminergic neurons from the substantia nigra (SNpc)
What is the primary cell type in the caudate-putamen complex and what type of neuron are they?
Medium Spiny Neurons (MSNs) and they are GABAergic
What is the globus pallidus and its two subsections?
-it makes up the pallidum and had the globus pallidus interna and the globus pallidus externa
What is the GPi?
structure packed with inhibitory or GABAergic motor neurons that project to the motor thalamus
What is the GPe?
structure packed with inhibitory GABAergic neurons that projects to the STN or the subthalamic nucleus
What is the STN?
it is a nucleus packed with excitatory Glutamatergic neurons that project back to the GPi
What is the substantia nigra, what does it do, what it is color?
-where dopamine production and synthesis in the brain occurs, has a dark color due to chemical byproducts of dopamine production, and has the dopaminergic neurons which project to the striatum
What is the major cell type in the striatum (caudate-putamen complex) and the basal ganglia overall?
medium spiny neurons MSNs and they are GABAergic
What dopamine receptors do MSNs in the striatum express?
D1 receptors and D2 receptors
What are D1 receptors?
-they are receptors that bind dopamine and correspond to the direct pathway for signaling; are metabotropic receptors and they promote the activity of adenylate cyclase in the cell with the net result of signaling via these receptors being the initiation of movement
What are D2 receptors on MSNs?
bind dopamine and they correspond to the indirect pathway for signaling they are also metabotropic meaning GPCR and they INHIBIT the activity of adenylate cyclase in the cell causing the net result of termination of movement
What is the Direct pathway?
the cortex and and SNpc —excitatory (Glu +) and DA+—–striatum—-GABA- —-GPi——GABA- —–Thalamus —-Glu+—-Cortex
initiate movement
What is the indirect pathway?
Cortex and SNpc ——Glu_, DA- ——-Striatum—–GABA- ——-GPe—–GABA - ——–STN—Glu+——–GPi——GABA- ——-Thalamus —–Glu+——-Cortex
terminate movement
What is a hypokinetic disorder?
Parkinsons Disease
What causes Parkinsons Disease?
decreased dopamine production in substantia nigra causing less DA signaling via the direct pathway
What drug was used to treat Parkinsons Disease?
L-Dopa but they began to show hyperkinesis
What are other new methods of treatment to promote dopamine synthesis in the SNpc for PD?
deep brain stimulation
What are two hyperkinetic disorders?
Huntington’s Disease and Hemiballism
What is Huntington’s Disease?
-autosomal dominant genetic disorder that comes from the expansion of the CAG trinucleotide repeat which causes uncontrollable movements meaning deterioration of the inhibitory D2 pathway sue to loss of MSNs in the D2 pathway
What is hemiballism?
result of a unilateral brain injury or stroke which affects the STN causing uncontroallable body movements on one side since the STN is doing less excitatory signaling causing less inhibition by the GPi of the thalamus causing the thalamus to not lees excite but actually still excite the motor cortex
What part of the basal ganglia is implicated in non motor functions?
ventral side
What are the three major non motor functions the basal ganglia is involved in?
decision making and executive functioning, reward learning, motivation
How does the basal ganglia modulate decision making?
during adolescence when the connections between the frontal and limbic corticies begin to take shape and become more refined
How does the basal ganglia modulate reward learning?
-one of the most important limbic functions which is via signaling in the ventral aspects of the basal ganglia which is the nucleus accumbens and the ventral tegmental area, thought to play a role in addicition
How does the basal ganglia modulate motivation?
this is due to the fact that the basal ganglia is the dopamine hub of the brain or CNS
