3 - Basal Ganglia Flashcards by Tyler Brown

Basal Ganglia: Refers to structures that yield

distinctive kinds of movement disorders when damaged

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Basal Ganglia: Prefixes & suffixes that describes the course of fibers, e.g.:

Striopallidal
Corticostriate
Pallidothalamic
Nigroreticular

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Caudate

3 parts: head, body and tail

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Putamen coincides with

insula

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Globus pallidus has extensive

BG output to thalamus

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Structures Related to the Basal Ganglia

Caudate

C-shaped
Part of wall of lateral ventricle
3 parts: head, body and tail

Putamen

Globus pallidus

Substantia nigra
(not shown)

Subthalamus
(not shown)

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The caudate nucleus is large nucleus with a

head, body and tail portion. In fact, the word caudate means “having a tail”.

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As you can see in panel A, the caudate is the medial part of the striatum and projects into the

lateral ventricle. It has a large head in the anterior horn of the lateral ventricle and it tapers to a tail in the inferior horn of the lateral ventricle. The caudate has numerous interconnections with prefrontal cortex and other cortical association areas as such it is more involved in cognitive functions and less involved in motor functions. How is the shape of the caudate nucleus consistent with its functionality and pattern of connectivity?

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Substantia Nigra two parts

compact, reticular

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Substantia Nigra: Compact

Densely packed, pigmented neurons

Provides diffuse modulatory, dopaminergic projections to striatum

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Substantia Nigra: Reticular

Closer to cerebral peduncle, non-pigmented neurons

A basal ganglia output nucleus

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Basal Ganglia Related Movement Disorders: Involuntary movement,

hyperkinetic disorders

Chorea, athetosis, ballismus

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Basal Ganglia Related Movement Disorders: Difficult initiating

movement

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Basal Ganglia Related Movement Disorders: Perturbed

muscle tone
General ↑in flexor and extensor tone; rigidity of Parkinson’s disease
If tone ↑ in some muscles body can be bent\twisted into abnormal, fixed posture; dystonia
Tone can be decreased as well

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Huntington’s Disease (chorea): Degeneration of

striatum (caudate> putamen)

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Huntington’s Disease (chorea):

Chorea, rigidity, cognitive disturbances

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Huntington’s Disease (chorea): Autosomal

dominant, trinucleotide repeat

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Huntington’s Disease (chorea): Age of onset is variable, most at about

50 years of age

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4 Basic circuits of the basal ganglia: Circuits include

multiple, parallel loops that modulate cortical output

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4 Basic circuits of the basal ganglia: Cortical start & end points determine

loop function: i.e., motor, cognition, limbic (emotion/ motivation)

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4 Basic circuits of the basal ganglia: 1. Motor loop:

learned movements

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4 Basic circuits of the basal ganglia 2. Cognitive loop:

motor intentions

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4 Basic circuits of the basal ganglia 3. Limbic loop:

emotional aspects of movement

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4 Basic circuits of the basal ganglia: 4. Oculomotor loop:

voluntary saccades

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Basal Ganglia Motor Loop: BG cannot initiate

movements, but active during all movements

Basal Ganglia Motor Loop: Role in motor control is to influence

descending motor pathway, by modulating cortical activity (in motor areas) - Scales strength of muscle contractions - With SMA organizes requisite sequences of excitation of motor cortex needed for movement

Basal Ganglia Motor Loop: Two recognized pathways:

Direct pathway- 5 sets of neurons | Indirect pathway- 7 sets of neurons

BG loops: Cognitive loop: Role in

motor learning, planning movements ahead, especially when intended movement is complex

BG loops: Cognitive loop: When the new motor task is practiced to the point it can be

“automatically ” executed the motor loop (using putamen) becomes active instead

BG loops: Limbic loop: From inferior prefrontal cortex  thru

ventral striatum (nucleus accumbens)  ventral pallidum  DMN (MDN)  inferior prefrontal cortex

BG loops: Limbic loop: Gives expression to

emotions | E.g. smile, gesture, aggressive posture

BG loops: Limbic loop: Rich in

dopaminergic neurons, their loss may account for expression-poor facies of Parkinson patients

BG loops: Oculomotor loop: SNpr is tonically

active when eyes are fixed on an object

BG loops: Oculomotor loop: When a saccade is about to start the

oculomotor loop is activated, disinhibiting the superior colliculus

Neuronal connectivity: The presence of neurons with

inhibitory and excitatory neurotransmitters in the same neural pathway is key in fine tuning pathway output

Neuronal connectivity: A) Excitatory neuron 1

activates inhibitory neuron 2, which consequently silences neuron 3

Neuronal connectivity: B) A second inhibitory neuron

(2b) is placed into the pathway Note this has the opposite effect on neuron 3, because 2b is silenced Silencing 2b releases neuron 3 and it fires an action potential In the human brain neuron 3 is often a spontaneously firing neuron and this so-called disinhibition provides a means to regulate these neurons

Disinihibtion is a major feature of

neuronal activity in the basal ganglia

Basic Circuit of the Basal Ganglia | (direct pathway) : Input:

Cortical afferents to striatum (& subthalamus)

Basic Circuit of the Basal Ganglia (direct pathway) Outputs:

globus pallidus interna (GPi) (& substantia nigra reticular (SNr))

Direct Pathway 1. 1)Excitatory corticostriate fibers activate

inhibitory neurons in striatum

Direct Pathway 2. 2) Striatum inhibits

GPi (& SNr, not shown)

Direct Pathway 3. 3) Thalamus

disinhibited

Direct Pathway 4. 4) Thalamus activates

cortex

Direct Pathway 5. 5) Increased

cortical output

Indirect Pathway (normal)

1 & 2) cortical input & striatal output 3)↓GPe output 4 & 5) ↑ thalamic inhibition 6 & 7) ↓cortical output

Indirect Pathway (Subthalamus damaged)

Loss of subthalamic fibers (4) disinhibits thalamus (5), results in failure to suppress cortical outputs (6) and involuntary movement, i.e. hemiballismus (7)

Hemiballismus

Dramatic movement disorder

Hemiballismus: Limb movements are:

Flailing, rotatory | Often affect one side of body, may affect arm and leg to different degrees

Hemiballismus: Most often in

older patients

Hemiballismus: Due to a

cerebrovascular accident (CVA, stroke); branch of posterior cerebral artery

Direct and indirect pathways: Putamen and globus pallidus are

somatotopically organized

Direct and indirect pathways: This organization allows: | Via the direct pathway the

selective facilitation of neurons mediating a desired movement ….

Direct and indirect pathways: This organization allows: | While the indirect pathway simultaneously

disfacilitates other neurons that would have cause unwanted movements

Direct and indirect pathways: This organization allows: | The subthalamic nucleus is very important in

suppressing unwanted movements by somatotopic projections to globus pallidus interna

Parkinson’s Disease: Need 2 of 3 cardinal features:

Bradykinesia, resting tremor, rigidity

Parkinson’s Disease: Age of onset

about 60 years

Parkinson’s Disease: substantia nigra compact part

neurons contain Lewy bodies

Direct pathway and substantia nigra: Nigrostriatal fibers have

2 types of synapses on striatal projection neurons based on dopamine receptor expression (D1 or D2)

Direct pathway and substantia nigra: Striatal projection neurons in

direct pathway express D1 receptors, are facilitatory

Indirect pathway and substantia nigra: Striatal projection neurons in the

indirect pathway express D2 receptors, are inhibitory

Indirect pathway and substantia nigra: Because SN is tonically active the

direct pathway is normally favored and more active

Role of Substantia Nigra: SN facilitation of direct pathway makes

SMA active prior to movement occurring

Role of Substantia Nigra: Action potentials from SMA to

primary motor cortex

Role of Substantia Nigra: In primary motor cortex a cerebello-thamalocortical projection enhances

CST and corticoreticular neurons prior to their discharge of an action potential

Since PD patients have difficulty performing movements, it is thought that the

putamen stores learned motor programs, which it assembles in the necessary sequence for the desired movement to occur and it transmits this information to the SMA

Levodopa to Treat

Parkinson’s Disease

Levodopa: Idea is to replace

dopamine lost due to degeneration of nigrostriatal fibers

levodopa: Helpful, but response can

fluctuate over time and can induce involuntary movement

Treatment of Parkinson’s Disease:

VA/VL and GPi are deep in the brain and near internal capsule; risky to lesion selectively Stem cells Deep brain stimulation

Treatment of Parkinson’s Disease: Deep brain stimulation

Implant electrodes in subthalamus to provide long-term stimulation and overcome abnormal activity in these structures

Internal part of globus pallidus and compact part of SN are

continuous