Basal Ganglia

Question 1

Why is the term “basal nuclei” more accurate than “basal ganglia”?

Answer 1

• basal nuclei is more accurate as it describes a collection of cell bodies within the CNS and the basal ganglia are located within the brain
• ganglia refers to cell bodies of neurones located outside the CNS / in the periphery

Question 2

Where do signals for movement originate from?

How do the basal ganglia influence these signals?

Answer 2

• signals for movement originate in the cerebral cortex, but are modulated by a variety of subcortical structures
• the subcortical structures (including the basal ganglia) ensure that movements are appropriate (e.g. timing, force, speed)

Question 3

What is the primary function of the basal ganglia?

What other structure is involved in allowing this to happen?

Answer 3

• the primary function is to provide a feedback mechanism to the cerebral cortex for the initiation, control and cessation of the motor response (movement)
• the basal ganglia is invovled in the modulation of voluntary movement
• it can only provide a feedback mechanism to the cortex via the thalamus

Question 4

Where does the basal ganglia receive inputs from?

What different types of outputs can it send and what does this depend on?

Answer 4

• the basal ganglia receives a copy of the package of intended movement created by the cortex
• it receives and interprets this information relating to the direction and amplitude of movement
• it then relays the decision to move via the thalamus:

1. it can excite the cortex to facilitate wanted movement
2. it can dampen down the cortex to inhibit unwanted movement

• the basal ganglia (via the thalamus) can either be excitatory or inhibitory to the cortex depending on what type of movement is appropriate at any given time

Question 5

What are the 5 structures of the functional basal ganglia?

What do they have in common?

Answer 5

1. caudate nucleus
2. putamen
3. globus pallidus
4. substantia nigra
5. subthalamic nucleus

• they all share connections and are all involved in the modulation of voluntary movement

Question 6

What structures are encompassed by the corpus striatum (“striped body”)?

Answer 6

corpus striatum = neostriatum + paleostriatum

(Neo)striatum:

• this is a term used to refer to the caudate nucleus and the putamen
  
  • they act together as one structure

Paleostriatum:

• this refers to the globus pallidus, which can be divided into 2 parts:

1. globus pallidus internus (GPi)
2. globus pallidus externus (GPe)

• the globus pallidus and the putamen together form the lentiform nucleus
  
  • this is because they have the appearance of the lens / lentil

Question 7

Where is the substantia nigra found and how can it be divided into 2 parts?

Answer 7

• located within the midbrain

Substantia nigra pars reticulata:

• contains diffuse neurones and appears pale in colour

Substantia nigra pars compacta:

• contains dopaminergic neurones that are clustered close together
• appears dark in cross-section as melanin is produced as a by-product of dopamine production

Question 8

What parts of the corpus striatum and substantia nigra are functionally the same?

Answer 8

• the substantia nigra pars reticulata and globus pallidus internus are functionally the same
• they are referred to as one structure as they have exactly the same function, even though they are in anatomically different locations

Question 9

What is the difference between the primary and secondary functions of the basal ganglia?

Answer 9

Primary function:

• involved with the normal initiation, control and cessation of voluntary movement

Secondary functions:

• involved with the cognitive and emotional aspects of movement
  
  • e.g. how someone’s body language reflects the way they are feeling

Question 10

Describe the neurones and structures involved in the default circuit of the basal ganglia

What needs to be done in order to initiate movement?

Answer 10

Structures involved:

• cortex sends a package of intended movement to the input nuclei
  
  • these are the caudate nucleus + putamen (neostriatum)
• the input nuclei relay this information to the output nuclei
  
  • these are the GPi + SNr
• the output nuclei send connections to the thalamus

The thalamus is the ONLY structure that is capable of communicating with the cortex

Neurones involved:

• the neurones travelling from the thalamus to the cortex are excitatory
  
  • if these were active all the time, we would be moving all the time
• the thalamus is dampened down by inhibitory neurones travelling from the output nuclei

To initiate movement, we need to remove the inhibition of the thalamus by the output nuclei

• the default state is inhibition of the thalamus, which can be removed or enhanced depending on whether movement is required or not

Question 11

What happens if there is a lesion to the basal ganglia?

What are the 2 different types of lesion?

Answer 11

dyskinesia - abnormal, involuntary movements

Hypokinetic lesion:

• occurs when a lesion causes the outputs from the basal ganglia to be excessive
• this leads to movement being slowed

Hyperkinetic lesion:

• occurs when a lesion causes the outputs from the basal ganglia to be reduced
• this leads to abnormal and involuntary movements that occur during rest

Question 12

How can the locations of the thalamus and caudate nucleus be described using the ventricular system as a landmark?

Answer 12

• the thalamus forms the lateral border of the III^rd ventricle
• the caudate nucleus follows the C-shape of the lateral ventricle and is located lateral to the anterior horn and body
• the tail of the caudate nucleus forms the roof of the inferior horn of the lateral ventricle

Question 13

What structure lies lateral to the caudate nucleus and what lies lateral to this?

Answer 13

• the internal capsule is located lateral to the caudate nucleus
• the lentiform nucleus is located lateral to the internal capsule
• from medial to lateral:*

1. lateral ventricle (most medial)
2. head of caudate
3. internal capsule
4. lentiform nucleus (most lateral)

Question 14

What 3 structures make up the corpus striatum?

How are they connected?

Answer 14

1. globus pallidus
2. putamen
3. caudate nucleus

• the globus pallidus and the putamen together form the lentiform nucleus
• the putamen and the caudate nucleus are separate, but are connected in several locations by cellular bridges
  • these structures have the same embryological origin so started as one single mass of grey matter

Question 15

What are the relationships between the caudate nucleus and the lateral ventricle?

Answer 15

• the caudate nucleus is C-shaped and follows the course of the lateral ventricle
• the head and body of the caudate form the lateral wall of the lateral ventricle (anterior horn and body)
• the tail of the caudate forms the roof of the inferior horn of the lateral ventricle within the temporal lobe

Question 16

Where is the septum pellucidum found?

What can be seen if this is removed?

Answer 16

• the septum pellucidum spans fron the corpus callosum** to the **columns of the fornix
• if the septum is removed, the lateral ventricle is exposed
• this allows viewing of the caudate nucleus, which is located lateral to the lateral ventricle
• to view the tail of the caudate nucleus, we would need to enter the temporal lobe

Question 17

What is represented by 4, 5, 13 and 14 in this superior cadaver view?

Answer 17

• 5 is the septum pellucidum which lies between the 2 exposed lateral ventricles
• the body grey matter lateral to the lateral ventricle is the caudate nucleus (4)
• lateral to the caudate nucleus are fibres of the internal capsule (14)
• lateral to the internal capsule is the lentiform nucleus (13)

Question 18

What is used as a landmark when looking at the corpus striatum in different planes?

How can the putamen and globus pallidus be distinguished from each other?

Answer 18

ventricular system

• the head of the caudate nucleus forms the lateral border of the lateral ventricle (anterior horn / body)
• the tail of the caudate nucleus forms the roof of the inferior horn of the lateral ventricle
• the globus pallidus is medial to the putamen and is smaller in size

it also stains paler than the putamen (globus pallidus means “pale globe”)

Question 19

Complete the diagram

Answer 19

Question 20

What is the claustrum, extreme capsule and external capsule?

Name the structures from lateral to medial starting at the insula

Answer 20

• the insula is the grey matter cortex located most laterally
• the extreme capsule is a thin layer of white matter located medial to the insula
• the claustrum is a layer of grey matter located medial to the extreme capsule
• the external capsule is a thin layer of white matter located medial to the claustrum and lateral to the putamen
• From lateral to medial:*

1. insula
2. extreme capsule
3. claustrum
4. external capsule
5. putamen
6. globus pallidus
7. internal capsule
8. thalamus

Question 21

Where does the putamen originate and extend to?

What separates the putamen and caudate nucleus?

Answer 21

• putamen originates at the level of the head of the caudate and extends posteriorly to the posterior third of the thalamus
• the anterior limb of the internal capsule separates the head of the caudate (medial) from the putamen (lateral)
• the anterior limb is absent rostrally, so the head of the caudate and the putamen are fused

Question 22

Where is the globus pallidus located in relation to the internal capsule?

What are the functions of the medullary laminae?

Answer 22

• it is located immediately medial to the putamen and lateral to the internal capsule
• the apex** of the globus pallidus sits against the **genu of the internal capsule
• the posterior limb of the internal capsule separates the globus pallidus from the thalamus
• the lateral medullary lamina separates the globus pallidus from the putamen
• the medial medullary lamina separates the globus pallidus into external and internal segments

Question 23

Where is the subthalamic nucleus located?

Answer 23

• it is located inferior and slightly lateral to the thalamus
• it is almost in the region of the midbrain, but it is part of the diencephalon

Question 24

What is the difference in the ways the 2 components of the substantia nigra stain?

Where is the internal capsule located at the level of the midbrain?

Answer 24

Pars compacta:

• this is the most posterior part of the substantia nigra
• it stains dark due to the presence of dopaminergic neurones
  • melanin is produced as a by-product of dopamine production

Pars reticulata:

• located anterior to the pars compacta
• the neurones located here are more diffuse and it does not stain as dark

Internal capsule:

• the fibres of the internal capsule are located lateral to the substantia nigra as the cerebral peduncles
• the cerebral peduncles are continuous with the internal capsule

Question 25

What neurones travel from the cortex to the basal ganglia?

Answer 25

**_corticostriatal neurones_** * they travel from the cerebral cortex to the **_input nuclei_** of the basal ganglia (**caudate** and **putamen**) ***Corticostriatal neurones travel from the cortex to the _neostriatum_*** * the putamen is involved in the pure motor aspect of movement * the caudate has additional roles in the emotional and cognitive processing of movement

Question 26

Where do striatal neurones travel to and from? What is their function?

Answer 26

* striatal neurones originate from the **_caudate nucleus_** or **_putamen_** and travel to the **_globus pallidus_** (**internus or externus**) * striatal neurones are **_INHIBITORY_** * they **do not do anything by themselves** unless they are stimulated * when they are activated by an afferent neurone, they release **inhibitory neurotransmitter**s to inhibit the neurone that they are targeting

Question 27

What are the afferent connections to the striatum?

Answer 27

* corticostriatal neurones * nigrostriatal neurones * thalamostriatal neurones

Question 28

What type of neurotransmitter is released by the corticostriatal neurones? What information do they carry?

Answer 28

* corticostriatal neurones travel from the cortex to the **_striatum_** (**caudate + putamen**) * they are carrying information about **_intended movement_** * they secrete **_excitatory neurotransmitters_** that will excite the striatal neurones

Question 29

What is the difference in corticostriatal neurones that project to the putamen and caudate nucleus?

Answer 29

**_Putamen:_** * receives corticostriatal neurones from the **primary motor** and **sensory** areas * *these are somatotopically organised* **_Caudate nucleus:_** * receives corticostriatal neurones from **association areas**, **limbic areas** and the **frontal eye field**

Question 30

Where do nigrostriatal neurones travel from? What neurotransmitter do they release and what is the action of this?

Answer 30

* they travel from the **substantia nigra _pars compacta_ (SNc)** to the striatum * they release _dopamine_ as a neurotransmitter ***Nigrostriatal neurones can be either _excitatory or inhibitory_ depending on the _receptor_ expressed by the striatal neurone they come into contact with*** * if they come into contact with a striatal neurone expressing a **_D1 receptor_**, they are **_excitatory_** * if they come into contact with a striatal neurone expressing a **_D2 receptor_**, they are **_inhibitory_**

Question 31

Where do thalamostriatal neurones originate from and what is their effect?

Answer 31

* they originate from the **_centromedian nucleus_** of the thalamus and run to the striatum * they are always **_excitatory_**

Question 32

What is meant by the term "pallidum"? What are the 3 types of neurone that connect to the pallidum?

Answer 32

* the "pallidum" refers to both the **_external and internal parts_** of the **globus pallidus** * connections to the pallidum include: 1. **pallidothalamic** neurones 2. **subthalamopallidal** neurones 3. **pallidosubthalamic** neurones

Question 33

Where do pallidosubthalamic and subthalamopallidal fibres travel to and from? How do they travel there?

Answer 33

**_Pallidosubthalamic fibres:_** * travel from the **globus pallidus _externus_ (GPe)** to the **subthalamic nucleus** * these fibres are always **_INHIBITORY_** **_Subthalamopallidal fibres:_** * travel from the **subthalamic nucleus** to the **globus pallidus _internus_ (GPi)** * these fibres are always **_EXCITATORY_** ***Neurones travelling to and from the subthalamus do so in the _subthalamic fasciculus_***

Question 34

Describe the 2 different pathways of the pallidothalamic fibres Where do they travel to and what is their function?

Answer 34

* pallidothalamic fibres travel from the **_GPi_ (and SNr)** to the **thalamus** * some fibres leave the GPi and pass **_inferior_ to the subthalamic nucleus** - these travel within the **_ansa lenticularis_** * some fibres leave the GPi and pass **_superior_** **to the subthalamic nucleus** - these travel within the **_lenticular fasciculus_** * just before they reach the thalamus, the ansa lenticularis and the lenticular fasciculus **come together** to form the **_thalamic fasciculus_** * the thalamic fasciculus projects to the **_VA, VL & centromedian nuclei_** of the thalamus ***Thalamocortical neurones are always excitatory, but they are always being _INHIBITED_ by _pallidothalamic neurones_ from the GPi & SNr***

Question 35

How do the basal ganglia influence movement? What is the default state of the thalamus at rest and how can this be changed to allow for movement?

Answer 35

* to influence movement, the basal ganglia function primarily through **balancing inhibition** and **disinhibition** of **thalamocortical pathways** * *the basal ganglia can only influence movement via the thalamus* * the default state is that the **_thalamus is always under inhibition_** * thalamocortical neurones are **inhibited by _pallidothalamic neurones_** from the **GPi and SNr** * the default state is to **not produce any movement** at all * in order to initiate movement, the **_inhibition of the thalamus needs to be removed_**

Question 36

What is the difference between the direct and indirect pathways? When do they occur?

Answer 36

**_Direct pathway:_** * facilitates **ongoing movements** that are **required** and **appropriate** * leads to **_excitation_** of the cortex from the thalamus **_Indirect pathway:_** * **inhibits unwanted movements** * leads to **_inhibition_** of the cortex from the thalamus ***These pathways work simultaneously and are both occurring all of the time***

Question 37

What is the difference in the activity of (neo)striatal neurones and pallidothalamic neurones?

Answer 37

**_Striatal neurones:_** * these pass from the **striatum** (putamen & caudate nucleus) to the **globus pallidus** (GPe or GPi) * they are **inhibitory** but are **_quiescent_** - they do not exert an effect unless they are activated by something else **_Pallidosubthalamic neurones:_** * these pass from the **GPi & SNr** to the **thalamus** via the ansa lenticularis or lenticular fasciculus * they are always **inhibitory** and are **_always active_** * they **_inhibit excitatory thalamocortical neurones_** that travel from the thalamus to excite the cortex * *this is the default state that inhibits movement*

Question 38

What is the difference in the structures involved in the indirect and direct pathways?

Answer 38

* the direct pathway passes directly from the **input nuclei** (caudate / putamen) to the **output nuclei** (SNr / GPi) * the indirect pathway **_makes a stop at the GPe_** before reaching the **output nuclei**

Question 39

Describe the neurones involved in the direct pathway

Answer 39

* **_corticostriatal neurone_** projects from the cortex to the **input nuclei** (caudate / putamen) this neurone is **_excitatory_** to the **quiescent striatal neurones** * striatal neurones are activated and begin to release **inhibitory neurotransmitters** * inhibitory neurotransmitters from the striatal neurones **_decrease_ the activity of _pallidothalamic neurones_** * as pallidothalamic neurones are **inhibitory**, when their activity decreases, there is **_less inhibition_ of thalamocortical neurones** * thalamocortical neurones are able to **_excite the cortex_**, which can initiate a movement program via the **corticospinal / corticobulbar pathways** ***This pathway facilitates wanted movement by _removing inhibition of the thalamus_***

Question 40

Describe the neurones involved in the indirect pathway

Answer 40

* corticostriatal neurones excite a **quiescent striatal neurone** passing from the **input nuclei** to the **_GPe_** * the activity of the inhibitory striatal neurone is increased * the inhibitory striatal neurone **inhibits the _pallidosubthalamic neurone_** passing from the **GPe** to the **subthalamic nucleus** * as the activity of the inhibitory pallidosubthalamic neurone is decreased, this **removes the inhibition** of the **excitatory _subthalamopallidal neurone_** * the subthalamopallidal neurone passes from the **subthalalmus** to the **GPi / SNr** * the subthalamopallidal neurone excites the **_inhibitory pallidothalamic neurone_** * increasing the activity of the pallidothalamic neurone **_enhances the inhibition of the thalamus_** and further decreases the activity of the thalamocortical neurone ***This pathway inhibits unwanted movement by _enhancing the inhibition of the thalamus_***

Question 41

When is dopamine required in movement? Where does this come from?

Answer 41

* dopamine is required when we want to **_initate a movement from rest_** * a big burst of dopamine will **massively excite the cortex**, allowing for the initiation of movement * dopamine is released by **_nigrostriatal neurones_** that travel from the **substantia nigra pars compacta** (SNc) to the **striatum** (caudate / putamen)

Question 42

How does the effect of dopamine depend on which receptor it comes into contact with?

Answer 42

* **dopamine + D1 receptor = excitation** * **dopamine + D2 receptor = inhibition** * dopaminergic inputs facilitate the **_initation of movement_** via both the **direct** and **indirect pathways**

Question 43

What neurone expresses a D1 receptor? What happens when dopamine comes into contact with this receptor?

Answer 43

* D1 receptors are expressed by **striatal neurones** of the **_direct pathway_** * When dopamine comes into contact with a D1 receptor, the effect is to be **_excitatory_** to these neurones * the striatal neurone is being excited to a higher extent, so will exert a **greater inhibitory effect** on the **pallidothalamic neurone** * this leads to **_enhancement of the excitation of the cortex_**

Question 44

What neurone expresses a D2 receptor? What happens when dopamine comes into contact with this receptor?

Answer 44

* D2 receptors are expressed by **striatal neurones** of the **_indirect pathway_** * when dopamine comes into contact with a D2 receptor, the effect is to be **_inhibitory_** to that neurone * inhibition of the inhibitory striatal neurone **increases the activity** of the **pallidosubthalamic neurone** * there is **greater inhibition** of the **subthalamopallidal neurone**, which can no longer excite the inhibitory pallidothalamic neurone * the activity of the inhibitory pallidothalamic neurone goes down, which **removes the inhibition of the thalamus** * thalamocortical neurones are now able to excite the cortex

Question 45

How does dopamine influence the direct and indirect pathways? What happens if there is an injury to the SNc (or it is diminished)?

Answer 45

**_Excitation of direct pathway:_** * dopamine has **excitatory effects** on **D1 receptors** of fibres travelling from the striatum to the **GPi** **_Inhibition of indirect pathway:_** * dopamine has **inhibitory effects** on **D2 receptors** of fibres travelling from the striatum to the **GPe** ***Injury to the SNc leads to a person being _unable to initiate movement_***

Question 46

What are the 4 main symptoms of Parkinson's disease and why do they occur?

Answer 46

1. bradykinesia / hypokinesia 2. resting tremor 3. rigidity 4. expressionless face * symptoms result from a **_dopaminergic deficit_**

Question 47

What is bradykinesia and why does this occur in Parkinson's disease?

Answer 47

* this describes **slow / decreased movement** with **_difficulty to initiate movement_** * there is increased latency times before movement * it occurs due to a **decrease in dopamine** leading to an **_increased output_** from the **_GPi / SNr_** to the **thalamus** * there is difficulty initiating movement as the **thalamus is being inhibited** by the pallidothalamic neurones

Question 48

Why do rigidity and resting tremor occur in Parkinson's disease?

Answer 48

**_Resting tremor:_** * cause not well understood but thought to involve tremor cells located in several basal ganglia nuclei **_Rigidity:_** * cause not well understood but thought to result from reduced cortical excitation leading to reduced inhibition of the reticulospinal pathway via corticoreticular fibres * the reticulospinal pathway controls muscle tone

Question 49

What is meant by a hyperkinetic disorder?

Answer 49

* excessive motor activity leads to **_increased involuntary movements_** and **_decreased muscle tone_**

Question 50

Why does Huntingdon's disease (chorea) occur? How does it present?

Answer 50

* it occurs due to the **_degeneration of inhibitory striatal neurones_** travelling to the **_GPe_** (indirect pathway) * it is an **inherited** dominant illness that involves a defect in the **huntingtin protein** * it presents as **wild, uncontrolled movements** of the **_distal limb_** that are abrupt and jerky * it can happen **_bilaterally_** as it is inherited and there can be degeneration of neurones on both sides

Question 51

Why does hemiballismus occur? What does this present as?

Answer 51

* occurs due to **_degeneration of the subthalamic nucleus_**, usually as a result of **vascular injury** * presents as **involuntary, ballistic movements** that appear suddenly * can involve the **proximal and distal limbs** but only affects the side **_contralateral to the lesion_** * most common causes are **ischaemic / haemorrhagic stroke** and **nonketotic hyperglycaemia** (diabetes)