Unit 6 - Basal Ganglia

Question 1

Overview of co-ordination of movement

Answer 1

Question 2

Function of basal ganglia

Answer 2

Role in shaping and refining movement

Facilitates a single target movement, while broadly inihibiting competing motor activities

Helps monitor and co-ordinate slow, sustained contractions related to posture and support

Inhibits muscle tone throughout the body

no direct connection to spinal cord (APs via pre and primary motor cortex)

Question 3

What motor neurons are influenced by basal ganglia

Answer 3

Basal ganglia controlling motor output - influences firing of gamma motor neurons

Question 4

Where are the medium spiny neurons found

Answer 4

In the striatum (input to BG)

Question 5

What is the output of BG

Answer 5

Pallidum

• Globus pallidus - internal
• Substantia nigra pars reticulata (SNpr)

Question 6

Other structures associated with BG

Answer 6

Subthalamic nucleus

Substantia nigra pars compacta - SNpc

Globus pallidus - external

Question 7

Where does the striatum NOT receive input from

Answer 7

Auditory and visual are the only cortical areas not projecting to striatum

Question 8

What is the corticostriatal pathway responsible for

Answer 8

Cortical input from most areas - particularly association areas

Question 9

Caudate input from

Answer 9

Multimodal association area and motor areas that control the eye

Question 10

Putamen input from

Answer 10

Somatic sensory cortices and premotor and motor cortex and visual and auditory association area

Question 11

Overview of input to BG

Answer 11

Question 12

What are the major output nuclei of BG

Answer 12

GPi

SNpr (from CAUDATE) - control of head movement

They connect to superior colliculus to control movement

Question 13

What structure is responsible for head movement

Answer 13

Caudate → SNpr

Via superior colliculus

Question 14

How do BG influence motor cortex

Answer 14

Via inhibition of tonic firing of thalamic nuclei

Question 15

Inhibitory

Answer 15

GABA

Question 16

Excitatory

Answer 16

Glutamate

Question 17

Overview of output

Answer 17

Question 18

What is the circuit within the basal ganglia

Answer 18

Cortex → striatum → GPi → Thalamus → cortex

Direct pathway

Thalamus is tonically active but under inhibitory control by BG

Question 19

Overall function of basal ganglia

Answer 19

BRAKE

Under normal circumstances the basal ganglia acts as an inhibitory control on the thalamus

slow down firing of the thalamus onto the premotor cortex so that movement is smooth, not jerky

Thalamus is tonically active and if left alone would continuously activate the cortex to carry out movement

Basal ganglia inhibits this tonic activity and dampen down activity to frontal cortex

Question 20

How is movement carried out via the direct pathway

Answer 20

Activate caudate and putamen

Inhibit BG output (specifically GPi)

Disinhibit thalamus

Enhanced signals to motor cortex

Question 21

What is the direct pathway responsible for

Answer 21

Excitatory signal that facilitates target movement

Cortex → striatum → GPi/SNpr → thalamus → cortex

DA (via D1 receptors) from SNpc facilitates direct pathway

Question 22

Where is the motor plan created

How is it executed

Answer 22

Created in pre motor cortex

This will excite and send glutaminergic projections to the caudate and putamen, activating neurons within this C/P brain region

Medium spiny neurons - gabanergic (inhibitory) - send more inhibiton to Gpi

Hence inhibit output of Gpi

Less APs to thalamus

Thalamus is free to fire, sending glutaminergic proejctions to the frontal cortex - MOVEMENT

Question 23

What does dopamine act on

Answer 23

D1 receptors (located on medium spiny neurons)

• facilitates activity

Enhances activity of medium spiny neurons

Question 24

What facilitates the direct pathway

Answer 24

DA via D1 receptors

Question 25

What is the indirect pathway

Answer 25

Responsible for broad inhibition of other motor activity Cortex → striatum → subthalamic nucleus → GPi/SNpr → thalamus → cortex Overall enhances inhibitory output from BG Dopamine (via D2 receptors) INHIBITS the indirect pathway Balance between direct & indirect pathway - facilitates expression of intended movement

Question 26

Nature of neurons within GPi

Answer 26

Inhibitory Dampen down activity in thalamus Hence activation of GPi - we'll increase inhibitory tone of thalamus and hence decrease movement

Question 27

How to increase activity of GPi

Answer 27

INDIRECT Stimulation of caudate & putamen will in turn activate medium spinae neurons which act to inhibit Gpi segment We decrease firing on internal segment - less inhibitory tone Less inhibitory tone onto the subthalamic nucleus As a result the subthalamic nucleus is DISINHIBITED - able to fire - sends GLUTAMINERGIC projections to internal segment We stimulate the internal segment, inhibiting movement

Question 28

Relationship between direct and indirect pathway

Answer 28

Activate direct pathway Disinhibit the thalamus, allow it to fire, carry out to movement In order to inhibit competing motor movements - activate indirect pathway Increase activity of internal segment, more gabergic tone, inhibiton of thalamus, less firing to frontal cortex and less movement Dopamine modulates activity within striatum Via 2 types of receptors

Question 29

MCQ

Answer 29

Question 30

How does dopamine modulate BG circuits

Answer 30

Substantia nigra pars compacta Dopamine facilitates direct pathway (D1 - increase cAMP) and inhibits indirect pathway (D2 - decrease cAMP) Modulates cortical input to striatum Overall facilitates movement

Question 31

Difference in 2 types of MSNs

Answer 31

MSN that project to the direct pathway are those that contain D1 receptors MSN that project to the INDIRECT pathway contain D2 receptors

Question 32

What effect does Parkinsons have on control of movement

Answer 32

Loss of nigrostriatal dopamine pathway Results in imbalance within basal ganglia Circuitry - increased inhibitory outflow of BG Movement is difficult to initiate and difficult to terminate - hypokinetic Dyskinesia - decreased voluntary and increased involuntary movement Resting tremor Diminished facial expressions Reduced arm swing

Question 33

Overview of Parkinsons Disease

Answer 33

Question 34

Pathophysiology of Huntington's Disease

Answer 34

Autosomal dominant - hyperkinetic Degeneration of medium spiny neurons - in particular those that project to the GPe - the INDIRECT pathway associated with basal ganglia GPe is overactive - decreased output from STN - inhibitory output is reduced - motor cortex is activated by inappropriate, jerky movements

Question 35

mHtt and neuroinflammation

Answer 35

Question 36

Overview of Huntingtons Disease

Answer 36

Less tonic inhibition Thalamus fires more readily

Question 37

MCQ

Answer 37