Structure and Function of the Basal Ganglia

Question 1

EP system

Most movement disorders involve…

Answer 1

Basal ganglia

Question 2

EP system

components

Answer 2

Basal ganglia
Thalamus
STN
Substantia Nigra
Red nucleus

Question 3

PMC

fun

Answer 3

execution of movement

Discharges prior to onset of muscular activity

Question 4

Cerebral cortex

List of outputs

Answer 4

(i) Corticospinal tract

(ii) Corollary projections:
(a) Premotor cortex-supplementary motor cortex (SMA)
(b) Somatosensorycortex
(c) Thalamus
(d) Putamen
(e) Cerebellum

Question 5

Supplementary motor cortex

Fun/lesion

Answer 5

a. Formulation of “motor program”
b. Anterior frontal lobe
c. SMA lesions cause akinesia (paucity of movement) and mutism

Question 6

Bereitschaftspotential (“readiness potential”)

chars

Answer 6

a. Slow negative potential on EEG
b. Seen over bilateral SMA and PMC in scalp recordings
c. Occurs during early preparation for self-initiated voluntary movement
d. Precedes muscular activity by several hundred milliseconds

Question 7

Basal ganglia

fun

Answer 7

Basal Ganglia have a major role in filtering motor programs
(1) Optimizes motor programs

Active during both preparation and movement
(2) Integrates sensory and other information to filter motor program

No role in motor decisions or basic parameters of movement

Activated during imaginary motor actions

Question 8

Cerebellum

fun

Answer 8

(1) Dynamically adjusts motor execution

Adjusts many basic parameters of movement

(i) Velocity, acceleration, deceleration
(ii) Force

Important for automaticity and repetitive movements

Question 9

Thalamus

fun

Answer 9

(1) Relays information to and from cortex

a. Feedback from basal ganglia
b. Feedback from cerebellum
c. Primary sensory inputs

Question 10

Brainstem and SC

Motor outputs

Answer 10

Outputs to α- and γ- motor neurons

Outputs to segmental spinal motor circuits

Question 11

Striatum

Made up of…

Answer 11

Caudate

Putamen

Nucleus accumbens (not imp for mvmnt disorders)

Question 12

Basal Ganglia

Direct pathway

Answer 12

(i) Cortex: glutaminergic neurons stimulate striatum (ii) Striatum: GABAergic neurons inhibit tonically active GPi & SNpr (pallidum)
(iii) Pallidum: GABAergic neurons reduce inhibition of thalamus
(iv) Thalamus: disinhibited glutaminergic neurons stimulate cortex

Question 13

Basal ganglia

Indirect pathway

Answer 13

(i) Cortex: glutaminergic neurons stimulate striatum
(ii) Striatum: GABAergic neurons inhibit tonically active GPe
(iii) Gpe: GABAergic neurons reduce inhibition of STN
(iv) STN: glutaminergic neurons stimulate GPi & SNpr (pallidum)
(v) Pallidum: GABAergic neurons inhibit thalamus
(vi) Thalamus: inhibited glutaminergic neurons reduce cortical stimulation

Question 14

Basal ganglia

Newer concepts of the pathways

Answer 14

(i) The direct pathway encompasses both a “central” positive feedback loop and a sort of “surround inhibition” on competing movement elements by collateral innervation of interneurons
(ii) A “hyperdirect” pathway of cortico-STN connections also contributes to the inhibition
(iii) A “GPe-STN-GPi network” modulates the excitability of the GPi output neurons

Question 15

Topographic organization of corticostriatal projections

Answer 15

a. Source of cortical afferents predicts the area of densest innervation in the striatum
b. The total area of striatal innervation is an elongated zone which can extend the entire length of the striatum
c. Projections from different areas of cortex converge or diverge in the striatum, depending on their origin

Question 16

Sensorimotor areas

How are they organized

Answer 16

somatotopically

Question 17

Sensorimotor areas

loc

Answer 17

(i) Motor and sensory homunculi of the cortex are projected in register onto the lateral putamen
(ii) Feet are dorsal, face is ventral

Question 18

Oculomotor function

Subserved by…

Answer 18

(i) frontal & supplementary eyefields project to the caudate
(ii) many neurons in the caudate fire during saccadic eye movements

Question 19

Functional organization of corticostriatal projections

The putamen is the motor nucleus of the striatum

Answer 19

(i) Projections from motor and somatosensory cortex go primarily to the putamen
(ii) Neurons which fire during limb movement are more common in the putamen than caudate, and stimulation of discrete zones of the putamen produces limb movement

The caudate receives dense innervation from the prefrontal cortex
(i) The caudate may play a role in planning, memory-based and psychological aspects of basal ganglia function

Question 20

Parkinsons disease

Loc of lost neurons/consequence

Answer 20

Parkinson’s disease: more dopamine terminals lost in the putamen than caudate = motor dysfunction

Question 21

HD

Loc of lost neurons/consequences

Answer 21

Huntington’s disease: caudate degenerates early = cognitive & eye movement abnormalities

Question 22

Striosomes

Answer 22

Cortical input from layers V & VI
Prefrontal, insular & temporal cortex
Some axons go to dopaminergic neurons in SNc
GABAergic neurons with D1 & D3 receptors are common
High levels of Substance P and Dynorphin

Question 23

Matrix (matrisomes)

Answer 23

Cortical inputs from layer V and supragranular cortex
Sensorimotor & association cortex
Axons include outputs to direct and indirect pathways
GABAergic neurons with high D2 receptors are common
High levels of Enkephalin
Important for motor functions

Question 24

Medium spiny neurons

chars

Answer 24

90-95% of striatal neurons
4-5 primary dendrites with abundant spines (post-synaptic boutons)
Axon collaterals which arborize close to the soma
GABAergic, silent at rest
Primary axons projects outside the striatum

Question 25

Medium spiney neurons

How are the types distinguished

Answer 25

Three types distinguished by dopamine receptor type: D1, D2, D3

Question 26

Medium spiney neurons

D1 receptors

Answer 26

Substance P and dynorphin
Project to SNr and GPi
Primarily striosomal, but also matrisomal in the direct pathway

Question 27

Medium spiney neurons

D2 receptors

Answer 27

1) Enkephalins
2) Project to GPe
3) Primarily matrisomal, especially in the indirect pathway

Question 28

Medium spiney neurons

D3 receptors

Answer 28

Function uncertain

Question 29

Striatal interneurons

types

Answer 29

1) Cholinergic
1) Large spiney neurons
2) Interact directly with medium spiney output neurons
2) Somatostatinergic
1) Medium aspiney neurons
3) Both somatostatin & acetylcholine markers are denser in the matrix neuropil (matrisomes)

Question 30

D1 and D2 dopamine receptor families

Answer 30

D1 family: D1 & D5

(a) Dopamine is an excitatory transmitter
(b) Positive coupling to cAMP

D2 family: D2, D3, D4

(a) Dopamine is an inhibitory transmitter
(b) Negative coupling to cAMP

Question 31

Convergence vs Parallelism

Answer 31

(1) Anatomically, there is convergence with connections from many neurons to fewer neurons
(2) Physiologically, there are many parallel circuits which do not interact
(3) Removing the dopamine generates increasing communication between parallel circuits and creates convergence.

Question 32

Lesions causing hyperkinetic disorders

Answer 32

(1) Generally interrupt the indirect pathway, causing increased positive feedback to cortex

a. Lesions in the subthalamic nucleus cause hemiballism
b. Huntington’s disease disrupts the connection from the striatum to the lateral globus pallidus

Question 33

Lesions causing hypokinetic disorders

Answer 33

(1) Loss of dopaminergic input to the striatum in Parkinson’s disease increases activity in the indirect pathway while decreasing activity in the direct pathway, due to the differential effects of D1 and
D2 receptors

Question 34

Role of basal ganglia

Answer 34

Planning: modeling the motor program

Funneling (convergence) vs parallel processing

Basal ganglia = state feedback
Vs
Cerebellum = dynamic feedback