Basal Ganglia Flashcards
What is the function of the Basal Ganglia?
• Motor Functions
o Facilitate wanted movements
o Inhibit unwanted movements
• Do not directly influence LMNs
o Rather, indirectly influence UMNs
• Damage results in hypokinetic or hyperkinetic movement disorders
• Also related to cognitive functioning, emotions
What occurs in Huntingtons disease?
Degeneration of striatal neurons of the basal ganglia
What is the pathway of the basal ganglia?
→ Thalamus → Cerebral cortex (on same side)
CC influences UMNs (and muscles on the opposite side)
Basal ganglia indirectly influence UMNs & LMNs, hence indirectly control skeletal muscle
Describe the basic anatomy of the basal ganglia
Major components of the tel, di & mesencephalon:
- Caudate (tel)
- Putamen (tel)
Globus pallidus external and internal GPe GPi (Tel)
Subthalamus (di)
Substantia nigra pars compacta, pars reticulata SNc SNr (mes)
Describe the functional unit of the “striatum”
• Caudate + Putamen + Nucleus accumbens = striatum (functional unit)
o Collectively called the ‘striatum’ due to their striped appearance in many planes of section (due to bridges of gray matter growing across the internal capsule between the putamen and caudate nucleus), as well as their common origin and similar connections.
o Caudate nucleus is adjacent to the lateral ventricle. C shaped (like lateral ventricle)
Describe the Lenticular/lenitofrm nucleus
• Globus pallidus internal & external segments (GPi & GPe)
• Globus pallidus + putamen = lenticular (lentiform) nucleus
o Anatomical unit
Substantia Nigra is made up of:
- Pars compacta (SNc) = dopaminergic neurons (pigment in neurons = black)
- Pars reticulate (SNr) = lighter in colour
Give a brief overview of the connections between basal ganglia and the Cerebral Cortex
• Basal ganglia is interconnected with the cerebral cortex ipsilaterally
• Motor outflow of cerebral cortex is directed contralaterally
• Thus, basal ganglia affect contralateral side of body
Hence unilateral BG damage – symptoms on opposite side of body
Main input to Basal Ganglia
The major inputs come from the cerebral cortex, reaching the PUTAMEN, CAUDATE NUCLEUS & NUCLEUS ACCUMBENS & SUBTHALAMIC NUCLEUS.
Main output from the Basal Ganglia
outputs project from the internal segment of the globus pallidus and the reticular part of the substantia nigra to the THALAMUS which in turn projects back tot he cortex
Describe the circuitry of basal ganglia: Parallel Loops
Specific areas of the basal ganglia recieve specific cortical ;;oops.
Motor Cortex, premotor cortex and supplementary motor cortex act on ?
Putamen -> gPr etc -> VA/VL thalamus -> motor cortex
Frontal eye fields, association cortex act on?
Caudate-> Gp , SNr -> DM/VA thalamus -> frontal eye fields
Limbic cortex act on
Nucleus accumbens -> Gpi, SNr -> Intralaminar thalamus -> limbic cortex
Ie. Paralelle loops: Putamen is for
MOTOR FUNCTIONS
CAUDATE is for
COGNITIVE FUNCTIONS (association cortex) & EYE MOVEMENT (frontal eye fields)
NUCLEUS ACCUMBENS
Emotions, desires, mood and affect (limbic cortexx)
Describe the major ouput nuclei of the basal ganglia
GPi, SNr – major output nuclei of basal ganglia
- They are tonically active, releasing the inhibitory neurotransmitter GABA onto neurons of the thalamus (VA & VL and DM & intralaminar nuclei of thalamus) -> This inhibits the thalamus, and thus the cerebral cortex
Projections from thalamus.So the thalamus is ‘disinhibited’ and therefore can STIMULATE the cortex (use glutamate, an excitatory neurotransmitter)
Describe the “Direct Pathway”
FACILITATES CORTICAL OUTPUT thru DISINHIBITION
Net effect is to excite the cotex. Facilitates cortical output
Cortex releases glutamate —-< striatum releases GABA —–] globus pallidus internus, substantia nigra reticularis (less active, hence they are releasing LESS inhibitory GABA hence less INHIBITION of the thalamus —-] thalamus (causes sending of glutamate thru disinhibition) —< Cortex
Describe the INDIRECT PATHWAY
INHIBITS CORTICAL OUTPUT- net effect
(1)
Cortex releases glutamate —–< striatum releases GABA —–] globus pallidus externus releasing less GABA—] subthalamus —-< globus pallidus internus and substantia nigra reticularis —-] thalamus —–< cortex
(2)
Cortex —-< subthalamus —–< GPi, SNr —–] thalamus ——<cortex
Describe the effect of SNc on direct and indirect pathways
SNC = input to the basal ganglia, supplying the striatum with dopamine.
SNc facilitates the direct, excitatory pathway (hence promotes movemet)
SNc inhibits the indirect pathway (inhibits the inhibitory pathway, so it promotes movement)
SNc contains dopaminergic neurons
===all up FACILITATES OUTPUT of CORTEX
How can Dopamine be excitatory and inhibitory in the Substantia Nigra pars compacta?
Different receptors on neurons in the striatum ->
D1: stimulates adenylate cyclase, cyclic AMP, hence more likely to depolarise and fire and AP
D2: inhibits adenylate cyclase
Describe SNc action on the direct path
cortex —-< striatum + (SNc dopamine D1 receptors) –] GPi, SNr —-] thalamus —–< cortex
Parkinsons Disease is a disorder of the basal ganglia- describe
• Chronic degeneration of dopaminergic neurons of SNc • Cause: in most cases unknown o Genetic: alpha-synuclein, other genes o Environmental causes? (MPTP, rotenone) • Symptoms: ‘TRAP’, progressive o Tremor (resting) o Rigidity o Akinesia/hypokinesia/bradykinesia o Postural instability – takes a while for the other neurons to fire
Parkinsons Disease - describe the degeneration of SNc in Parkisons disease
Leads to
• Reduced output from direct pathway (less facilitation)
• Increased output from indirect pathway (more inhibition)
• This seems to explain the akinesia, hypokinesia, bradykinesia
Note the models of basal ganglia circuitry don’t explain the resting tremor (alternating contraction of agonist/antagonist muscle pairs)
Parkinsons Disease: treatment
• Dopamine precursors (L-DOPA) or agonists, or inhibitors of metabolism of dopamine
• Surgical destruction of, or electrode implants into, certain nuclei
o To compensate for loss of neurons
• Experimental approaches
Huntingtons disease is a disorder of basal ganglion- discuss
• Degeneration of striatal neurons (GABAergic)
• Cause: genetic (autosomal dominant)
o Can also be a new mutation
o Expanded CAG repeats (poly-gIn) in Huntington gene
• Codes for the amino acid glutamine
• This increased glutamine in proteins is toxic to neurons
Describe symptoms of Huntingtons disease
• Chorea (dance-like movements)
o Direct pathway – now have less stimulation of the cortex → cant control voluntary neurons as well (doesn’t explain chorea)
o Indirect pathway – facilitates cortical output by losing striatal neurons. Cortex is overactive so you get this chorea form movements
• Decline in cognitive function
• Personality change
Treatment of Huntingtons
• Aim is to inhibit chorea
o Pharmacologically give them Parkinson’s disease so they stop writhing
• Dopamine antagonists (haloperidol)
• Dopamine depletion (reserpine)
What is the blood supply of the basal ganglia?
Perforating branches of the Circle of Willis
Lenticulostriate arteries from middle cerebral artery
Anterior choroidal artery
