Basal ganglia Flashcards
Components of the basal ganglia
- Striatum (caudate, putamen)
- Globus pallidus
- Substantia nigra
- Subthalamic nucleus
Dominant cell in the striatum
-Medium spiny stellate neurons
Inputs, outputs, and markers of medium spiny stellate neurons in the striosome
- Inputs: Limbic cortex, Substantia nigra- pars compacta (SNpc)
- Outputs: SNpc
- Markers: GABA, no ACh
Inputs, outputs, and markers of medium spiny stellate neurons in the matrix
- Inputs: cortex, interneurons, SNpc
- Outputs: GPe and GPi
- Markers:GABA, D2, ACh
Input structures of the basal ganglia
- Striatum and subthalamic nucleus
- Direct projections from the cortex
Output structures of the basal ganglia
- Globus pallidus internal (GPi)
- Substantia nigra pars reticulada (SNpr)
- Project back to the cortex via the thalamus
Intermediate structures of the basal ganglia
- SNpc
- Subthalamic nucleus
Cortico-basal ganglia circuits bike analogy
- Idea initiated in the cortex (pedals)
- Idea translated to the input layer of the basal ganglia (front sprocket)
- Chain passes to the output layer (rear break, always on)
- Then passed to thalamus (rear sprocket)
- SPpc cells (dopamine) keep the chain moving
Direct cortical-basal ganglia-thalamo-cortical circuit
-Cortex to striatum: excitatory projection
(at this point D1 from SNpc also contributes to excitatory projection)
-Striatum to GPi/SNr: inhibitory projection
-GPi/SNr to thalamus: Inhibitory projection
-Thalamus to cortex: Excitatory projection
Indirect cortical-basal ganglia-thalamo-cortical circuit
-Cortex to striatum: excitatory projection
(at this point D1 from SNpc contributes an inhibitory projection)
-Striatum to GPe: Inhibitory projection
-GPe to STN: Inhibitory projection
-STN to GPi/SNr: Excitatory projection
-GPi/SNr to thalamus: Inhibitory projection
-Thalamus to cortex: excitatory projection
Parallel segregated basal ganglia loops
- Basal ganglia loops are anatomically segregated and distinct
- Influence essentially all functions
Motor loop
-Motor cotex–>putamen–>lateral GP, internal segment–>ventral lateral and ventral anterior nuclei
Oculomotor loop
-Posterior parietal prefrontal cortex–>body of caudate–>GPi, SNpr–>mediodorsal and ventral anterior nuclei
Prefrontal loop
-Dorsolateral prefrontal cortex–>anterior caudate–>GPi, SNpr–>mediodorsal and ventral anterior nuclei
What is activated during difficult planning and visuomotor control?
-Basal ganglia–Globus Pallidus
Hyperdirect path
- Allows cortex to directly excite the subthalamic nucleus, bypasses the striatum
- Uses excitatory glutamine
Striosomal path
- Involved in habit learning
- Giant cholinergic interneurons–tonically active neurons (TANs)
- Interact with DA inputs of SNpc at the level of medium spiny stellate neurons (ACh enhances dopamine release)
- Activated by rewards–part of neural substrate underlying behavioral reinforcement
Hyperkinetic disorders
- Abnormally low levels of BG output (disinhibits the thalamus)
- Excessive motor activity
- Huntington’s, sydenham’s,athetosis, hemmiballismus, dystonia, tourettes
Hypokinetic disorders
- Excessive inhibition of the thalamus by the BG
- Impairment of initiation of movement (akinesia)
- Reduction in the amplitude and velocity of movement (bradykinesia)
- Parkinson’s
Sydenham’s chorea
- Caused by autoimmune reaction to childhood infection with group A B-hemolytic streptococci (occurs in 25% of patients with acute rheumatic fever)
- Recovery in 50% of cases in 2-6 month
- Striatum is the site of attack
- aka PANDAs
Huntington’s disease
- Autosomal dominant
- Atrophy of neostriatum especially the enkephalin-expressing neurons in the caudate
- HD kills ENK neurons in the striatum which leads to unchecked D1 tone–increases drive to M1–hemiballistic movements
Cells impacted in Parkinson’s
- Locus coeruleus cells die first, then pars compacta cells
- Loss of dopamine causes a hyperactive break which impairs and slows movement
Huntington’s treatment
- Block excess action of direct pathway
- Anti-dopaminergic or dopamine-depleting drugs: haldol, olanzapine, tetrabenazine
Parkinson’s treatment
- Dopa won’t cross BBB so give L-DOPA
- Only helps in the short term–can cause abnormal movements and/or hallucinations
- Dopamimetics
- MAO-B/COMP inhibitors–prevent degradation of DA
- Anti-cholinergics
- Palllidotomy or thalamotomy
- Fetal nigral transplantation
- Deep brain stimulation
