Basal Ganglia Flashcards by Matthew Miller

What are the main nuclei of the basal ganglia?

Striatum - STR
Globus Pallidus - GP
Subthalamic nucleus - STN
Substantia Nigra - SN

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What nuclei make up the globus pallidus?

Externus - GPe and Internus - GPi. GPi is very similar to SNr

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What nuclei make up the substantia nigra?

Pars compacta - SNc

Pars reticulata - SNr

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What is the general function of the basal ganglia?

They are 4 interconnected nuclei which influence motor behavior by regulating activities of upper motor neurons

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What is the striatum derived by and what two parts make it up? What separates them?

Derived from telencephalon.

Made up of caudate nucleus medially and putamen laterally, separated by anterior limb of internal capsule in high mammals. They are stuck together in lower animals.

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Where is the caudate nucleus spatially located? What is its shape?

Medial to anterior horn of internal capsule / putamen, lateral to lateral ventricle. Has a head, body, and tail. Tail is alongside the inferior horn of the lateral ventricle in the temporal lobe.

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Where is putamen positioned?

Lateral to head of caudate + thalamus, does not enter temporal lobe.

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Where is the globus pallidus located? What greater structure do these nuclei make up?

Located medial to the putamen. GP + putamen = “lentiform nucleus”

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Where is the subthalamic nucleus located?

In diencephalon, ventral to thalamus and adjacent to posterior limb of internal capsule. Superior to substantia nigra.

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Where is the substantia nigra located, including the relationships with its smaller components?

Dorsal to cerebral peduncles in the ventral midbrain.

SNc is more dorsal, SNr is more ventral, serves as partner to GPi, the other efferent nucleus of BG.

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Why is substantia nigra called that?

“Dark substance” - due to melanin granules, a byproduct of dopamine production

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What is the main afferent center of the BG?

Striatum

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What is the main efferent center of the BG?

GPi/SNr

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What is the direct path of the basal ganglia and what is its function?

Activator of movement

Input -> striatum -> globus pallidus internus + substantia nigra pars reticulata -> output

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What is the indirect path of the basal ganglia and what is its function?

Suppressor of movement

Input -> striatum -> globus pallidus externus -> subthalamic nucleus -> globus pallidus internus + substantia nigra pars reticulata -> output

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What are the inputs to the STR? Include neurotransmitter

Corticostriatal - glutamate from cerebral cortex
Nigrostriatal - dopamine from SNc
Raphestriatal - serotonin from midbrain raphe nuclei
Thalamostriatal - glutamate from intralaminar (CM-PF) thalamus

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What does the SNr/GPi project to? What are the fibers called?

VA-VL thalamus
Pedunculopontine nucleus (PPN)

Called ansa lenticularis / lenticular fasciculus

What does the VA/VL thalamus do?

Projects glutamate to area 6 and area 4 for fine control of voluntary movement + stored motor programs

What does pedunculopontine nucleus (PPN) do?

Projects acetylcholine to brainstem motor pathways for posture, reflex, and gross movements of axis like swinging the arms. It’s the PPN of tegmentum, thus also called PPTg

Projects to medial reticulospinal tract in pons, and lateral reticulospinal tract in medulla

How do the functions of areas 6 and 4 differ?

6: Premotor - selects the proper program and coordinates multiple movements which are more complex
4. Specific voluntary control over contractions of individual muscles

How does area 6 influence the striatum?

Through the corticostriatal pathway, it activates goal-direct movements. Strong excitatory signals for STR neurons with a high activation threshold come from area 6. Once STR neurons start firing, area 6 shuts down.

What happens to STR neurons once they’re firing?

Their activities are adjusted via cerebellum, and they output back to areas 6 and 4 via the efferent pathway of the basal ganglia to keep the movement regulated. Areas 6 and 4 will again stimulate the BG.

What is the function of the GPi/SNr?

They are the “brake” of the output surgery, acting on the VA/VL/PPN via GABA to inhibit them. Their firing must be inhibited via STR?

What is the function of STR in the direct pathway?

Releases GABA on the GPi/SNr, to stop the GABA inhibition of the output circuit. This is called disinhibition and is required for movement.

How does STR disinhibit the indirect pathway as well?

When stimulated, releases GABA on the GPe, which inhibits the release of GABA onto the STN. Thus, the STN is allowed to excite the GPi/SNr, which "puts the brake" on the system once more.

How do the nigrostriatal dopament afferents differentially impact the STR pathway?

D1 receptors on striatal neurons enhance glutamate activation of the direct pathway D2 receptors on striatal neurons inhibit glutamate activation of the indirect pathway

How does the BG system contribute to saccadic eye movements?

From SNr to superior colliculus.

What are the two types of diseases which can be caused by basal ganglia dysfunction?

1. Hypokinesia - slow movements or no movements | 2. Hyperkinesia - dysfunctional uncontrolled movements

What causes Parkinson's disease?

Degradation of substantia nigra pars compacta (SNc). This causes decreased dopamine to striatal neurons, silencing the direct pathway and hyperactivating the indirect pathway, stopping movement

What are the symptoms of Parkinson's?

Slow movements, resting tremor (4-6 Hz), muscle rigidity like lead-pipe or cogwheel, abnormal gait and postural instability

What is the net effect of Parkinson's disease on the STR?

Hyperactivity, since both pathways are being activated by glutamate, but the indirect pathway is VERY overactive.

What condition develops after administration of L-DOPA for a few years?

L-DOPA induced dyskinesia, where abnormal hyperkinetic movements are performed from overactivation of the direct pathway.

What are two alternative treatments to Parkinsons?

1. Surgical destruction of GPi (pallidotomy) | 2. Deep brain stimulation (DBS) of overactive GPi or STN to reverse dysrhythmia of basal ganglia circuitry.

What causes hemiballismus? What are the symptoms?

Stroke which damages subthalamic nucleus STN unilaterally (removes activation of GPi/SNr). Will affect motor on contralateral side (since UMN swap sides). Symptoms: rapid, irregular muscle jerks of contralateral limbs and face. Resolves itself spontaneously within a few weeks after the lesion.

What is the inheritance and pathology of Huntington's?

Autosomal dominant, 100% penetrance. It destroys the STR nucleus, and also leads to thinning of the cerebral cortex. Without input from STR, the indirect pathway dies first. This causes dementia and psychosis, as well as chorea.

What are choreic movements?

Dance-like and graceful movements, which patients will try to hide by doing purposeful movements at the same time. Eventually, HD patients will become immobile and psychotic, and die within 10-20 years.

What is an ulterior function of the caudate nucleus/

Storage of habitual motor programs (non-declarative memory), i.e. tying shoes or riding a bike

What is the nucleus accumbens (NAc)?

Specialized area of ventromedial STR. It is involved in motor patterns of motivation behaviors, and is considered a pleasure center because it holds motor programs for behaviors easily reinforced (gambling, drug abuse). Dopamine makes these motor programs more active.

What phenomenon of parkinson's patients does the NAc explain?

Supplementation via L-DOPA can lead to increased desire for gambling.

How does the medial vs lateral STR differ?

Medial: Includes NAc and caudate -> more cognitive in function Lateral: putamen - purely motor in function