Lecture 19: Basal Ganglia: Anatomy and Pharmacology Flashcards
(42 cards)
Definition of basal ganglia
collection of subcortical nuclei (gray matter) deep within the brain
What does the basal ganglia do?
It modulates -movement -cognition -behavior (emotional changes) Still an area of active research
What are the anatomical components of the basal ganglia?
i. striatum (caudate and putamen)
ii. The pallidum (globus pallidus interna(medial) and externa (lateral))
iii. . Substantia nigra = pars compact and reticularis
iv. Subthalamic nucleus
Striatum
name gotten from the striation of fibers that separate the caudate and the putamen
i. caudate and ii. putamen
How are the anatomical components of basal ganglia organized?
From superior/anterior to inferior/posterior
Caudate
Putamen
Pallidum
Subthalamic nucleus
Substantia nigra (black colored in real life)
You really only see the subthalamic nucleus and the substantia nigra via coronal section
Where is the basal ganglia located?
Lateral to the thalamus
The pallidum
globus pallidus interna (medial) and externa (lateral
Substantia nigra
i. pars compacta: dopaminergic
ii. pars reticularis: GABAnergic
Easy to identify because it is black in gross section
Subthalamic nucleus:
helps modulate the interaction between the globus pallidus externa and interna
-lies ventromedial to the pallidum and above the substantia nigra
When activated, it inhibits GPi/SNr
How is basal ganglia organized in functionally?
a. input nuclei: caudate and putamen
b. output nuclei: Substantia nigra pars reticularis (SNr), Globus pallidus interna (GPi)
c. intrinsic nuclei: globus pallidus externa, substantia nigra pars compacta (SNc), Subthalamic nucleus (STN)
What sends input into the basal ganglia, specifically to caudate/putamen?
- M1
- Premotor cortex
- Supplementary motor areas
What sends output out of the basal ganglia?
Globus Pallidus interna and Substantia Nigra Pars Reticularis
Sends axons to VA and VL of thalamus, which eventually gets to the cortex
Lenticular nucleus
putamen and globus pallidus
-components of basal ganglia form numerous functional circuits or loops
Attenuation
reduce the force, effect, or value of
What is the Direct pathway? What nuclei are involved?
a. Initiates movement
b. Helps you learn of POSTIVIE outcomes associated with specific behaviors
- carried out by neurons in Globus Pallidus interna and Substantia Nigra Pars Reticularis (SNr)
- GPi/SNr normally inhibit neurons in the thalamus
- when cortex sends signal to striatum, striatum INHIBITS GPi/SNr, thereby DISinhibiting the neurons in thalamus
- the thalamus neurons then sends excitatory signal to cortex and increases cortical activity
- excitation of striatum leads to excitation of motor, premotor and supplementary motor areas
- SNc also participates by facilitating activation of striatum once striatum is activated by cortex
How does excitation of striatum lead to excitation of M1, premotor and supplementary areas? And does excitation of the striatum ALWAYS lead to excitation of cortex?
Excitation of striatum, which inhibits GPi/SNr, which DISinhibits (activates) VA/VL of thalamus, which activates M1
However, just keep in mind that excitation of striatum can lead to both direct and indirect pathways (or also to cortex inhibition as well)
What is the Indirect pathway? What nuclei are involved?
i. Terminates movement
ii. Helps you learn of NEGATIVE outcomes associated with specific behaviors
- increases basal ganglia (inhibitory) output
- excitatory signal reaches cortex, inhibits GPe and disinhibits subthalamic nuclei
- subthalamic nuclei excites GPi/SNr which inhibits thalamus
- DECREASED cortical activity
What is the role of Substantia Nigra Pars Compacta (SNc)
SNc is technically an inhibitor of the indirect pathway since it activates the direct pathway
SNc dopaminergic neurons always lead to cortical stimulation
Decreased SNc = DECREASED cortical stimulation
(decreased dopamine = decreased cortical stimulation)
What are the principal neurotransmitters for pars reticularis and pars compacta?
GABA from SNr (that’s why it inhibits thalamus)
Dopamine from SNc
What is Parkinson’s Disease?
Slow, progressive brain degeneration related to the accumulation of the protein alpha-synuclein into the cytoplasmic aggregates called Lewy bodies
- one of the most common basal ganglia diseases - most common form of disease is idiopathic
What is most common MOA of PD?
Loss of dopaminergic function from SNc
What are the key histological features of Parkinson’s?
Lewy bodies created by alpha-synuclein accumulation
How do patients who take MPTP (N-methyl-4-phenyl 1,2,3,6-tetrahydropyridine) get Parkinson’s? What is the treatment?
MPTP is oxidized into MPP+ by Mao-B (which normally metabolizes dopamine)
-uptake of MPP+ degenerates the dopaminergic neurons…MPP+ in mitochondria in neurons inhibit oxphosph and depletes energy stores, excess oxygen radicals, neuron death
Treatment: MAO-B inhibition
What are the motor features of Parkinson’s?
Cardinal motor signs:
a. Bradykinesia: slow initiation of voluntary movements
b. Rigidity: increased muscle tone (resistance to passive movement)
c. Resting tremor: “pill-rolling” (fingers move like they are rolling a pill)
d. Stooped and unstable posture
Diagnosis requires 2 out of 4 cardinal motor signs
