Basal Ganglia

Question 1

What is the function of the Basal Ganglia?

Answer 1

• 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

Question 2

What occurs in Huntingtons disease?

Answer 2

Degeneration of striatal neurons of the basal ganglia

Question 3

What is the pathway of the basal ganglia?

Answer 3

→ 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

Question 4

Describe the basic anatomy of the basal ganglia

Answer 4

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)

Question 5

Describe the functional unit of the “striatum”

Answer 5

• 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)

Question 6

Describe the Lenticular/lenitofrm nucleus

Answer 6

• Globus pallidus internal & external segments (GPi & GPe)
• Globus pallidus + putamen = lenticular (lentiform) nucleus
o Anatomical unit

Question 7

Substantia Nigra is made up of:

Answer 7

• Pars compacta (SNc) = dopaminergic neurons (pigment in neurons = black)
• Pars reticulate (SNr) = lighter in colour

Question 8

Give a brief overview of the connections between basal ganglia and the Cerebral Cortex

Answer 8

• 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

Question 9

Main input to Basal Ganglia

Answer 9

The major inputs come from the cerebral cortex, reaching the PUTAMEN, CAUDATE NUCLEUS & NUCLEUS ACCUMBENS & SUBTHALAMIC NUCLEUS.

Question 10

Main output from the Basal Ganglia

Answer 10

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

Question 11

Describe the circuitry of basal ganglia: Parallel Loops

Answer 11

Specific areas of the basal ganglia recieve specific cortical ;;oops.

Question 12

Motor Cortex, premotor cortex and supplementary motor cortex act on ?

Answer 12

Putamen -> gPr etc -> VA/VL thalamus -> motor cortex

Question 13

Frontal eye fields, association cortex act on?

Answer 13

Caudate-> Gp , SNr -> DM/VA thalamus -> frontal eye fields

Question 14

Limbic cortex act on

Answer 14

Nucleus accumbens -> Gpi, SNr -> Intralaminar thalamus -> limbic cortex

Question 15

Ie. Paralelle loops: Putamen is for

Answer 15

MOTOR FUNCTIONS

Question 16

CAUDATE is for

Answer 16

COGNITIVE FUNCTIONS (association cortex) & EYE MOVEMENT (frontal eye fields)

Question 17

NUCLEUS ACCUMBENS

Answer 17

Emotions, desires, mood and affect (limbic cortexx)

Question 18

Describe the major ouput nuclei of the basal ganglia

Answer 18

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)

Question 19

Describe the “Direct Pathway”

Answer 19

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

Question 20

Describe the INDIRECT PATHWAY

Answer 20

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

Question 21

Describe the effect of SNc on direct and indirect pathways

Answer 21

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

Question 22

How can Dopamine be excitatory and inhibitory in the Substantia Nigra pars compacta?

Answer 22

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

Question 23

Describe SNc action on the direct path

Answer 23

cortex —-< striatum + (SNc dopamine D1 receptors) –] GPi, SNr —-] thalamus —–< cortex

Question 24

Parkinsons Disease is a disorder of the basal ganglia- describe

Answer 24

•	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

Question 25

Parkinsons Disease - describe the degeneration of SNc in Parkisons disease

Answer 25

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)

Question 26

Parkinsons Disease: treatment

Answer 26

• 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

Question 27

Huntingtons disease is a disorder of basal ganglion- discuss

Answer 27

• 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

Question 28

Describe symptoms of Huntingtons disease

Answer 28

• 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

Question 29

Treatment of Huntingtons

Answer 29

• Aim is to inhibit chorea
o Pharmacologically give them Parkinson’s disease so they stop writhing
• Dopamine antagonists (haloperidol)
• Dopamine depletion (reserpine)

Question 30

What is the blood supply of the basal ganglia?

Answer 30

Perforating branches of the Circle of Willis
Lenticulostriate arteries from middle cerebral artery
Anterior choroidal artery