Basal Ganglia

Question 1

The basal nuclei (or basal ganglia) are large masses of grey matter situated in the cerebral hemispheres.
Anatomically, the basal nuclei include large subcortical masses of grey matter located within each cerebral hemisphere developing from telencephalon. They include:

Answer 1

☑ Caudate nucleus
☑ Lentiform nucleus, which consists of two functionally
distinct parts, the putamen and the globus pallidus
☑ Amygdaloid nuclear complex
☑ Claustrum
☑ [Diagram 1] [Diagram 2] [Diagram 3] [Diagram 4]

Question 2

The caudate nucleus and the lentiform nucleus together constitute the ____(a)____. This consists of two functionally distinct parts. The caudate nucleus and the putamen form one unit called the ____(b)____ (also known as neostriatum), while the globus pallidus forms the other unit, the ____(c)____ (a.k.a paleostriatum). Phylogenetically, the amygdaloid nuclear complex and claustrum are considered as ____(d)____.

Answer 2

(a) corpus striatum
(b) striatum
(c) pallidum
(d) archistriatum
[Diagram] [Diagram 2]

Question 3

Functionally, the basal nuclei comprise of structures, the lesion of which produces dyskinesias (abnormal involuntary purposeless movements). The structures included are:

Answer 3

• Corpus striatum
• The subthalamic nucleus (which is of diencephalic origin) is very closely linked to the basal nuclei and is regarded as belonging to this group.
• The substantia nigra (midbrain) is also closely linked, functionally, to the basal nuclei.
• Some masses of grey matter found just below the corpus striatum (near the anterior perforated substance) are described as the ventral striatum. The part of the globus pallidus, which lies below the level of the anterior commissure, is designated as the ventral pallidum.

Question 4

Caudate Nucleus Topography
It is a C-shaped mass of grey matter, consisting of a large head, body and thin tail. The nucleus is intimately related to the ____(a)____ ventricle. The head of the nucleus bulges into the anterior horn of the ventricle and forms the greater part of its ____(b)____. The body of the nucleus lies in the floor of the central part and the tail in the roof of the inferior horn of the ventricle.

Answer 4

(a) lateral
(b) floor

[Diagram 1] [Diagram 2]

Question 5

Caudate Nucleus Topography
The anterior part of the head of the caudate nucleus is fused, inferiorly, with the lentiform nucleus. Fusion of these two results in strands of grey matter passing through the descending fibres of internal capsule giving a striated appearance and hence the name ‘corpus striatum’ to denote caudate and lentiform nuclei. This region of fusion is referred to as the ____(a)____, which is continuous, inferiorly, with the anterior perforated substance. The anterior end of the tail of the caudate nucleus ends by becoming continuous with the ____(b)____ nucleus.

Answer 5

(a) fundus striati
(b) amygdaloid

[Diagram 1] [Diagram 2]

Question 6

The body of the caudate nucleus lies lateral to the to the ____(a)____ and medially to the ____(b)____, which separates it from the lentiform nucleus.

Answer 6

(a) thalamus
(b) internal capsule
[Diagram]

Question 7

State the relations of the lentiform nucleus.

Answer 7

Medially: Internal capsule
Laterally: Separated from the claustrum by fibres of the external capsule
NB: these capsules are so called because they appear, to the naked eyes, to form a covering or capsule for the lentiform nucleus
Superiorly: related to corona radiata
Inferiorly: sublentiform part of internal capsule
[Diagram]

Question 8

In this card, click the answer to link you to photos relating corpus striatum to the internal capsule.

Answer 8

Diagram 1
Diagram 2
Diagram 3
Diagram 4

Question 9

State the afferent connections of corpus striatum.

Answer 9

• The entire cerebral cortex via corticostriate fibres. These fibres are glutamatergic.
• The intralaminar nuclei of the thalamus via thalamostriate fibres
• The pars compacta of the substantia nigra via nigrostriate fibres. These fibres are dopaminergic.
• Noradrenergic fibres are received from the locus coeruleus.
• Serotoninergic fibres are received from the raphe nuclei (in the reticular formation of the midbrain).

Question 10

The main output of the corpus striatum is concentrated upon the pallidum and on the substantia nigra (pars reticularis). The outflow from globus pallidus forms four separate bundles. State these bundles.

Answer 10

~ Fasciculus lenticularis: it connects the globus pallidus internus to the thalamus and is a part of the thalamic fasciculus.
~ Ansa lenticularis arises from both the inner and outer segments of the globus pallidus and enters the subthalamic region where it meets the dentatorubrothalamic fibres and the fasciculus lenticularis. The union of the three tracts is called the thalamic fasciculus, which terminates in the ventral anterior (VA), ventral lateral (VL) and centromedian nuclei of thalamus [which then project to the motor and premotor areas of the cerebral cortex].
~ Subthalamic fasciculus consists of reciprocal connections between the globus pallidus and the subthalamic nucleus.
~ Some fibres from globus pallidus also pass to the substantia nigra (pallidonigral fibres).
~ [Diagram: afferent and efferent connections of the basal ganglia]
~ [Diagram: basal ganglia]

Question 11

State the functions of the corpus striatum.

Answer 11

1. It mediates enormous number of automatic activities involved in normal motor functions e.g. the maintenance of erect posture when sitting or standing.
2. It helps in smoothening the voluntary motor activity of the body.
3. It helps in maintenance of muscle tone.
4. It helps in prevention of involuntary movement.

Question 12

What is the claustrum?

Answer 12

This is a thin lamina of grey matter that lies lateral to the lentiform nucleus. It is separated from the latter by fibres of the external capsule. Laterally, it is separated by a thin layer of white matter from the cortex of the insula. It is functionally related probably to limbic system. [Diagram]

Question 13

The thin strip of white matter between the putamen and claustrum is called the ____(a)____, and the white matter separating the claustrum from the insular cortex is the ____(b)____.

Answer 13

(a) external capsule
(b) extreme capsule
[Diagram]

Question 14

What is the amygdaloid nuclear complex/amygdaloid body/amygdala?

Answer 14

It lies in the temporal lobe of the cerebral hemisphere and close to the temporal pole. It lies deep to the uncus and is related to the anterior end of the inferior horn of the lateral ventricle. It is functionally related to limbic system.

Question 15

State the connections of substantia nigra.

Answer 15

• The pars compacta of the substantia nigra sends a dopaminergic projection to the striatum (remember striatum is comprised of caudate nucleus and putamen).
• The pars reticularis projects to the ventral anterior nucleus of the thalamus. These impulses are relayed to frontal lobe of the cerebral cortex.
• Other efferents of the pars reticularis reach the reticular formation of the medulla and to the spinal cord.

Question 16

What is the clinical anatomy behind connections of substantia nigra?

Answer 16

The main connections (both afferent and efferent) of substantia nigra are with the striatum. Dopamine produced by neurons in the substantia nigra (pars compacta) passes along their axons to the striatum (mesostriatal dopamine system). Dopamine is much reduced in patients with a disease called Parkinsonism, in which there is a degeneration of the striatum.

Question 17

Connections of the basal nuclei with the cerebral cortex
Corticostriate fibres arise from all areas of the cortex, and terminate within the caudate nucleus, putamen and ventral striatum. Two basic circuits or loops link the cortex and basal ganglia; the direct loop and indirect loop. Describe these two loops.

Answer 17

a) The direct loop
♦ Glutamatergic cortical fibres project to the neostriatum
♦ GABAergic striatal efferents project to the GPi
♦ GABAergic efferents from the GPi project to the thalamus (VA and VL nuclei)
♦ Glutamatergic thalamic neurons project to the cerebral cortex

b) The indirect loop
♦ Glutamaterigic cortical fibres project to the neostriatum
♦ GABAergic efferents from the neostriatum project to the GPe
♦ GABAergic efferent from the GPe project to the subthalamic nucleus (STN)
♦ Glutamatergic neurons in STN, project to GPi and substantia nigra reticulata (SNr).
♦ GABAergic efferents from GPi and SNr project to the thalamus (VA and VL nuclei)
♦ Glutamatergic thalamic neurons project to cerebral cortex.

[Diagram 1]
[Diagram 2]

Important to Note:
1. Both corticostriate and thalamocortical projections are excitatory (glutamatergic). However, the efferents from the striatum to GPi and SNr, and their projections to the thalamus are inhibitory (GABAergic). Thus the overall effect of this loop is disinhibition of the thalamocortical projections (inhibit inhibitions = disinhibition), thus increasing the level of cortical activity.
2. Since the corticostriate and thalamocortical projections are excitatory, the GPe projections inhibitory, STN neurons excitatory, the overall effect of this indirect loop is to decrease the level of cortical activity.

Question 18

Remember that inferiorly, the caudate nucleus and putamen fuse to form the fundus striati. Therefore, the ____(a)____ striatum includes caudate nucleus and putamen. Immediately below the fundus striati, there is the olfactory tubercle (in the anterior perforated substance). More medially, there is a mass of grey matter called the nucleus accumbens. Therefore the nucleus accumbens and the olfactory tubercle comprise the ____(b)____ striatum.
The portion of global pallidus below the anterior commissure is called ____(c)____. The ____(b)____ striatum and ____(c)____ connect to the limbic lobe of cerebral cortex via anterior and medial nuclei of thalamus.

Answer 18

(a) dorsal
(b) ventral
(c) ventral pallidum

NOTES:
☑ The reason for considering the nucleus accumbens and the olfactory tubercle as parts of the striatum is that their connections are very similar to those of the main part of the striatum (or dorsal striatum).
☑ The nucleus accumbens, located in the ventral striatum is a part of the mesolimbic dopamine system. It has acquired importance following the recognition that this nucleus is concerned with simulating pleasure giving effects of addictive drugs (such as nicotine and alcohol).
☑ Nucleus accumbens again: [Diagram].

Question 19

State the blood supply of basal nuclei.

Answer 19

The basal nuclei are supplied by:
* Lenticulostriate branches of middle cerebral artery
* Anterior choroidal branch of internal carotid artery

Question 20

State the key functions of basal ganglia.

Answer 20

• promote and support patterns of behaviour and movement that are appropriate in the prevailing circumstances
• inhibit unwanted or inappropriate behaviour and movements

Question 21

Click on the Answer section to check once again on the basal ganglia circuitry. Please note that output nuclei of the basal ganglia are inhibitory.

Answer 21

[Diagram 1]
[Diagram 2]: Observe the inhibitory GABAergic neurons. Observe the two loops; direct and indirect loops.

KEY:
STN: Subthalamic nuclei
GpI: Globus pallidus internal part
GpE: Globus pallidus external part
SNr: Substantia nigra pars reticularis
SNc: Substantia nigra pars compacta

[Diagram 3]
[Diagram 4]
[Diagram 5]: This diagram also shows you the hyperdirect loop in addition to the direct and indirect loops.

Knowledge of the circuitry is important in understanding functions and disorders of basal ganglia.

Question 22

Give an overview of the basal ganglia organization. State the nuclei which are:
1. input
2. intrinsic
3. output
4. neuromodulator

Answer 22

1. Caudate and putamen [together the striatum]
2. • subthalamic nucleus (STN)
   • external segment of globus pallidus (GPe)
3. • substantia nigra pars reticularis (SNr)
   • internal segment of globus pallidus (GPi)
4. substantia nigra pars compacta (SNc)

Question 23

What is worth noting about the striatum, in terms of neurotransmitter and activity?

Answer 23

• GABAergic; inhibitory
• very little spontaneous activity

Question 24

What is the functional categorization of each of the two nuclei of the globus pallidus/what are they involved in? How can the neurons of the globus pallidus be described?

Answer 24

GPi: principal output nucleus
GPe: intrinsic circuitry

Neurons in both areas:
- high tonic firing rates
- GABAergic; inhibitory

Further notes:
~ Several firing patterns experimentally observed in neural populations have been successfully correlated to animal behavior. Population bursting, hereby regarded as a period of high firing rate followed by a period of quiescence, is typically observed in groups of neurons during behavior.
~ Generally speaking, tonic firing refers to a sustained response, which activates during the course of the stimulus.

Question 25

What is worth noting about subthalamic nucleus?

Answer 25

- it is the only **glutamatergic** nucleus among the basal ganglia circuit elements [excitatory] - target for deep brain stimulation *Further notes*: *Deep brain stimulation* is a method of treatment in which a surgically implanted device delivers electrical impulses to particular parts of the brain. It is used to reduce tremor and to block involuntary movements in patients with motion disorders by inhibiting overexcitement in the thalamus (especially in the treatment of multiple sclerosis) or globus pallidus (especially in the treatment of Parkinson's disease).

Question 26

What is worth noting about the nigral complex?

Answer 26

SNr: - GABAergic - output of basal ganglia - developmentally related to GPi SNc: - Dopaminergic - neuromelanin-containing cells - neuromodulator NB// SNc modulates motor movement and reward functions. As much as it is modulating and not part of the circuit, it is the source of the important nigostriatal dopamine pathway.

Question 27

State the role of basal ganglia in modulating movement.

Answer 27

The output nuclei of the basal ganglia (GPi/SNr) are **inhibitory.** Movement occurs when basal ganglia is **disinhibited**.

Question 28

What advantages does modulation through inhibition confer?

Answer 28

~ Strong tonic inhibition allows basal ganglia to serve as a master regulator - arbitrating between multiple excitatory inputs ~ Initiating and Discriminating

Question 29

Outline what happens when there's disinhibition of the basal ganglia.

Answer 29

~ output nuclei of the basal ganglia are **inhibitory** ~ output nuclei maintain a **high tonic level of discharge**, resulting in **suppression of activity in target regions** ~ **phasic decrease in firing rate** transiently **releases target regions from inhibition** ~ **disinhibited** thalamocortical circuit discharges, ending with **promotion of movement.**

Question 30

This is for understanding purposes, but ensure you understand, it is important. Click on Answer to view. Do not rate it a 5 until you understand it, and I know you will 😎.

Answer 30

**Direct pathway/loop facilitates action**, such that (refer to the circuit with the excitatory and inhibitory neurones shown): - there is cortical activation of the pathway - the glutamatergic neurons excite the striatum, stimulating it to inhibit GPi/SNr - since GPi/SNr is inhibited, it won't be able to inhibit the thalamus and in extent the cerebral cortex hence facilitating movement Indirect pathway suppresses action, how? - cortex excites the striatum (by glutamate neurotransmitters) - the striatum therefore inhibits GPe (globus pallidus external segment in case you forgot) - since GPe is inhibited, it won't have an effect on the subthalamic nucleus (STN) i.e. it won't inhibit the STN - therefore STN sends excitatory glutamatergic neurons to the GPi/SNr - since GPi/SNr is excited, it inhibits the thalamus and therefore the thalamus won't be able to excite the cortex hence suppressing movement/action.

Question 31

How do the direct and indirect pathways of the basal ganglia regulate motor output?

Answer 31

By action selection NB: ~ Co-activation of these pathways facilitates action selection through center-surround mechanism ~ Direct pathway inputs are focused and robust ~ Indirect pathway inputs are widespread and diffuse

Question 32

This card is for you understand action selection.

Answer 32

~ multiple/ambiguous stimuli in our environment often demand our attention/action ~ however, we're often confined to making a single action to address these stimuli (e.g. a saccade) NB: saccade - a rapid, conjugate, eye movement that shifts the center of gaze from one part of the visual field to another. Saccades are mainly used for orienting gaze towards an object of interest. Saccades may be horizontal, vertical, or oblique. ~ selection through surround inhibition likely occurs on large and small scales. this is important so that e.g. in this saccade example, it's not only saccade left or right, but **how far** to saccade?

Question 33

Briefly discuss the role of the SNc (substantia nigra pars compacta) in the basal ganglia pathway.

Answer 33

- it modulates the basal nuclei circuitry - it projects to the striatum, and utilises dopamine - dopamine facilitates the motor loop in two ways; ~ exciting the direct pathway ~ inhibiting the indirect pathway - the different effect on the two pathways is due to activation of two dopamine receptors in the striatum; D1 and D2. - D1 receptors are found on the striatal neurons giving rise to the **direct pathway** - D2 receptors are found on the striatal neurons giving rise to the **indirect pathway** - either way, this facilitates movement, but since it's a neuromodulator, could be why there's inhibition but some movement/action taking place (i.e. regulated) - the activity of the neurons within the pars compacta substantia nigra is related to the reward system and behavioral stimuli, so it is thought that they play a role in some forms of motor learning **NOTE:** ~ Thalamostriatal fibers also modulate the function of the basal ganglia ~ These fibers arise from the intralaminar nuclei of the thalamus and terminate primarily in the striatum. Besides that, some fibers terminate in the globus pallidus and in the subthalamic nucleus.

Question 34

What happens when dopamine input is lost?

Answer 34

~ direct pathway becomes less active; indirect pathway becomes more active ~ action selection (direct pathway) is suppressed; action inhibition (indirect pathway) is facilitated ~ in this case, one has a hypokinetic disorder, particularly Parkinson's disease in this case

Question 35

Motor behaviour is determined by the balance between direct and indirect striatal outputs. If the balance is lost, hypokinetic or hyperkinetic disorders arise. Different between the two (HINT: which has insuffienct or excess direct pathway output and hence vice versa of the indirect pathway output?)

Answer 35

Hypokinetic disorders: - insufficient direct pathway output - excess indirect pathway output Hyperkinetic disorders: - excess direct pathway output - insufficient indirect pathway output

Question 36

State the signs and symptoms associated with Parkinson's disease.

Answer 36

- bradykinesia (slowness of movement and speed (or progressive hesitations/halts) as movements are continued) - tremor at rest - rigidity - postural instability

Question 37

**Hyperkinetic disorders** a) What is chorea? b) State the causes of the following choreatic syndromes: I) Huntington's chorea II) Dystonia III) Tardive dyskinesia IV) Tourette's syndrome V) DOPA-induced dyskinesia VI) Hemiballismus c) List the choreatic symptoms

Answer 37

a) Chorea is a symptom that causes involuntary, random muscle movements that may be small and fidgety or big and vigorous. [Chorea was derived from Greek meaning *dance*.] b) I) Huntington's chorea - genetic (autosomal dominant) [**[Video](https://youtube.com/shorts/3l-Au2RHOvA?si=AWSqzT-4xPirbji-)**] II) Dystonia - genetic or idiopathic [**[Video: cervical dystonia](https://youtu.be/mSwo28t5t3k?si=GqI-fx19uAlQSheT)**] III) Tardive dyskinesia - chronic neuroleptic use [Tardive dyskinesia is caused by long-term use of neuroleptic drugs, which are used to treat psychiatric conditions. Tardive dyskinesia causes repetitive, involuntary movements, such as grimacing and eye blinking.] IV) Tourette's syndrome - excessive D2-subtype DA receptor expression V) DOPA-induced dyskinesia - Parkinson's therapy VI) Hemiballismus - unilateral vascular accident, typically subthalamic nucleus c) - chorea - athetosis (changeable or writhing movements) - dystonia (torsion spasm) - [[**Video: Clinical presentation of hemiballismus**](https://www.youtube.com/watch?v=7joAzT5Wfb8&pp=ygUNaGVtaWJhbGxpc211cw%3D%3D)] - [[**Video: Clinical presentation of Huntington's disease**](https://youtu.be/KleHA0fv0Eg?si=dzSjUJYIn1w1DoYM)] **NOTE**: Neuroleptics, also known as antipsychotic medications, are medications that block dopamine receptors in the nervous system. They are mainly prescribed to manage mental illnesses, such as schizophrenia and bipolar disorder, as well as psychosis.

Question 38

What is the difference between dopamine and acetylcholine as neuromodulators in the basal ganglia circuitry?

Answer 38

Dopamine: - facilitates action through both pathways (direct and indirect) - increases firing in response to reward directed cues Acetylcholine: - suppresses action through both pathways - decreases firing in response to reward directed cues