Motor Systems II: Basal Ganglia:

Describe the Basal Ganglia

• What is it?

• Location

• Associated Structures?

• Function?

Basal Ganglia:

• What is it?

  • Collection of telencephalic gray matter nuclei

• Location:

  • deep w/in white matter of cerebral hemipheres

• Associated structures:

  • subthalamus

  • nigral complex

  • pedunculopontine tegmental nucleus (PPTN)

• Function:

  • modulate cortical signals for:

    • General motor control

    • Eye movements

    • Cognitive functions

    • Emotional functions

Describe the Striatal complex

• Dorsal Complex:

  • Composition

  • Structure

  • Shape of Caudate

• Ventral Complex:

  • VS

    • Location?

  • NA

    • Main part of?

    • Location?

Dorsal Striatal Complex (Neostriatum)

• Composition:

  • Caudate & Putamen

• Structure:

  • Fused rostroventrally

  • Mostly separated by internal capsule

    • (except for cellular bridges)

• Shape of Caudate:

  • c-shape,

    • includes head, body & tail

  • follows lateral wall of lateral ventricle

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Ventral Striatal Complex:

• Ventral Striatum:

  • Location

    • ventral extension of caudate & putamen

    • below anterior commissure (AC) into substantia inominata

• Nucleus accumbens (NA):

  • main part of ventral striatal complex

  • Location:

    • rostroventraly

    • where putamen is cont. w/ caudate head

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NOTE:Olfactory tubercle (TIJ) & Islands of Calleja (IC): rostrolateral & caudal portion of anterior perforated substance (not on exam)

Describe the Pallidal Complex

• Dorsal Pallidum: Globus Pallidus

  • 2 segments?

  • What forms lenticular nucleus

  • What si the external medullary lamina

• Ventral Pallidum:

  • Location?

Dorsal Pallidum: globus pallidus

• 2 segments:

  • lateral: external segment

  • Medial: internal segment

  • Separated by internal medullary lamina

• Putamen + Dorsal Pallidum (GPI/E) = Lenticular nucleus

• External Medullary Lamina:

  • separates putamen from dorsal pallidum

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Ventral Pallidum: ventral pallidum

• Location:

  • ventral extention of globus pallidus

  • below anterior commissure → substantia innominata

Describe the Associated Nuclei

• Nigral Complex:

  • SN: Two parts? Describe them

  • VTA?

    • similar to? Contains?

• Subthalmic:

  • Location?

• PPTN

  • Location?

Nigral Complex:

• Substantia Nigra (SN):

  • Two Parts:

    • Pars Compacta (pc):

      • blackish appearance,

      • neurons contains neuromelanine,

        • product from dopamine (DA) oxidation

    • Pars Reticulata (pr):

      • similar to GPI

• Ventral tegmental area (VTA):

  • similar to SNpc

  • contain DA neurons

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Subthalamic Nucleus:

• Location:

  • ventral to Thalamus

  • above substantia nigra

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Pedunculopontine tegmental nucleus (PPTN):

• Location:

  • lateral portion of reticular formation

  • @ junction btw midbrain and pons

[REVIEW] Vasculature of Basal Nuclei

Describe the Input/outputs of Basal Ganglia:

• Input:

  • Arrive via?

  • Main input =?

  • Imp. DA inputs?

  • Other Inputs

• Output:

  • Leaves via?

  • Main Targets?

Inputs:

• arrive via the Striatum (dorsal/ventral)

• Main Input: cerebral cortex

• Imp. DA inputs:

  • dorsal,

  • SN pc

  • ventral,

  • VTA ( both brainstem)

• Other Inputs:

  • thalamus, brainstem (non Da)

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Outputs:

• Leaves via

  • medial segment of GPI

  • ventral pallidum

  • SNpr

• Main targets:

  • Thalamus

    • conveys info to cortex

    • return info to striatum

  • Brainstem Targets:

    • PPTN & superior colliculus

    • from SNpr

List and describe the function of Parallel circuits through basal nuclei, thalamus & cortex

1. Motor:

   • cortical & brainstem (PPTN)

   • control of body movements and posture

2. Oculomotor:

   • cortical & brainstem (superior colliculus)

   • control of eye movements

3. Prefrontal:

   • cognitive control of behavior

     • procedural memory + executive functions

4. Limbic:

   • reward system

   • control of biological drives (sex, food)

Describe the difference between direct/indirect pathways w/in basal ganglia

• Direct pathway:

  • Striatum → GPI / SNpr /ventral pallidum → Thalamus-cortex / brainstem

• Indirect pathway:

  • Striatum → GPE → Subthalamus → GPI / SNpr /ventral pallidum → Thalamus-cortex / brainstem

Describe the major tracts through the basal nuclei

• Internal Capsule

• Thalamic fasciculus

• Subthalamic fasciculus

major tracts through the basal nuclei

• Internal capsule

  • Corticofugal fibers (including corticostriatal)

  • Thalamocortical fibers

• Thalamic fasciculus

  • Pallido-thalamic fibers from:

    • Lenticular fasciculus

      • dorsal fibers (medial GPi),

      • go through internal capsule

    • Ansa lenticularis

      • ventral fibers (lateral GPi),

      • under internal capsule

• Subthalamic fasciculus

  • Pallido-subthalamic fibers (from Gpe)

  • Subthalamo-pallidal fibers (to Gpi)

Describe the NTs in the basal nuclei

• Caudate, putamen, nucleus accumbens, ventral striatum:

  • Direct path:

  • Indirect path:

  • Interneurons:

• Olfactory Tubercle & Islands of Calleja:

• Globus Pallidus & Ventral Pallidum:

• SNpr

• Subthalamic nucleus:

• SNpc + VTA:

• PPTN:

• Cortex & Thalamus:

• Caudate, putamen, nucleus accumbens, ventral striatum:

  • Projection neurons:

    • Direct path:

      • GABA (inhib)

      • SP (neuromodulator)

    • Indirect path:

      • GABA (inhibitory)

      • Enkephalin (ENK) (neuromodulator)

    • Interneurons: AcH (excitatory)

• Olfactory Tubercle & Islands of Calleja: GABA (Inhib)

• Globus Pallidus & Ventral Pallidum:

  • GABA (Inhib)

• SNpr

  • GABA (Inhib)

• Subthalamic nucleus:

  • GLU (excit.)

• SNpc + VTA:

  • Da (both)

• PPTN:

  • AcH (Inhib)

• Cortex & Thalamus:

  • GLU (Excit.)

What is Disinhibition?

Disinhibition = two inhibitions in a row → activation (indirectly)

Describe the difference in function of direct vs indirect pathways

Direct pathway:

• Function = increase thalamus activity → excitation of the corte

  • also act. PPTN + superior colliculus (brainstem)

• GO PATHWAY

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Indirect:

• Function = decrease thalamus activity → decrease activity of cortex

  • Also inhibits PPTN and superior colliculus.

• NO GO PATHWAY

Describe the role of Da and AcH in the Brain

• AcH:

  • Function of AcH in:

    • PPTN & LTN

    • Basal forebrain

    • Striatum

• Da:

  • 3 pathways: Describe Route/Fucntion:

    • Nigrostriatal

    • Mesolimbic

    • Mesocortical

AcH in Brain:

• PPTN & LTN

  • Action on brainstem + cerebellum + spinal cord

• Basal forebrain

  • Action on cortex

• Striatum

  • Action on basal ganglia function

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Da in Brain:

• 3 Pathways

  • Nigrostriatal

    • SNpc → dorsal striatum

    • Function: motor

  • Mesolimbic

    • VTA →

      • ventral striatum & nucleus accumbens

      • limbic cortex*

    • Function: Emotion & drives

  • Mesocortical

    • VTA → prefrontal cortex*

    • Function: cognitive

1. Describe the Role of Da and AcH in the Basal Ganglia

   • Da

   • AcH

2. Describe the difference in receptors for dopamine in direct/nondirect pathway

Dopamine:

• Da Neurons from:

  • SNpc → caudate & putamen (GABA)

  • VTA → NA (GABA)

---

Acetylcholine:

• AcH interneuson synapses on GABA projection neurons:

  • in caudate, putamen & NA

---

Da Receptors:

• Direct:

  • D1

  • Excitatory

• Indirect:

  • D2

  • Inhibitory

---

Da High vs Low:

• Da = High:

  • net effect = cortical activation

• Da = Low:

  • net effect = cortical inactivation

Describe the Role of Basal Nuclei on Movement

• Function

• Involved in?

• Basal Nuclei’s function

  • DOES NOT INITIATE MOVEMENT (cortex does)

  • affects Sub/cortical motor command outflow → change in motor behavior

• Involved in:

  • procedural (habit/skill) learning and memory

  • planning + execution of movement

    • facilitate actions that are:

      • goal-relevant

      • more appropriate

      • rewarded at a given time

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NOTE: Acetylcholine and dopamine may play a cooperative role in habit learning.

Finally, Draw out the Basal Ganglia Pathway

Compare and Contrast Hyper/Hypokinetic disease

• Mech

• Manifestation

• Examples

Hyperkinetic Disturbances

• Mech:

  • Overactivity in direct pathway

  • underactivity in indirect pathway

• Manifestation:

  • → excessive movement and decreased postural reflexes

• Examples: Huntington's disease, hemiballismus

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Hypokinetic Disturbances

• Mech:

  • Underactivity in direct pathway

  • overactivity in indirect pathway

• Manifestation:

  • generation of movement difficult and slow

  • increase postural reflexes → rigidity

• Example: Parkinson's disease

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NOTE: Because of the multiple basal ganglia pathways, the clinical manifestations of basal ganglia disorders often include prominent oculomotor, cognitive and psychiatric manifestations in addition to disorders of movement.

Describe Parkinson’s disease

• Symptoms:

  • List and describe the Major motor Symptoms

  • List the non-motor syndrome

• Describe the Neuropathology Findings

• Describe genetic Form of Parkinson

Symptoms:

• Major Motor Symptoms:

  • Tremor:

    • Shaking/trembling of limbs/face at rest

    • decrease during voluntary movement

  • Cogwheel Rigidity:

    • Muscles → contract → stiff, weak, sore

    • particularly those in limbs in trunk

  • Bradykinesia/akinesia:

    • Spontaneous, automatic movement is lost

    • all movement becomes extremely slow.

• Non-Motor Symptoms:

  • Dementia

  • Procedural memory loss

  • Reduced executive dysfunction

  • Mood, autonomic, sensory and sleep disturbances

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Neuropathological Finding

• loss of Da neurons in SNpc + VTA

• Remaining Da = contains cytoplasmic inclusions called Lewy bodies

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Genetic Forms of Parkinsons:

• Dominant mutation in gene (SNCA) for alpha- synuclein

  • protein found in Lewy Bodies

Describe the Mechanism for Parkinsons

Describe Huntington’s Disease

• What is it?

• Pathophysiology?

• Neurophysiology?

Huntington’s disease (Chorea)

• What is it?

  • Progressive + untreatable + 100% penetrance + Dominant Hyperkinetic Disease

• Pathophysiology:

  • 40 CAG repeat in HD gene (Chromosome 4) → expansion of polyglutamine tract of Huntingtin protein (htt) →

    • agglutination & deposits in neuron

    • glutamate excitotoxicity

• Neuropathology:

  • Loss of 90%+ of all neurons in striatum

    • Mostly affects projection neurons

  • Dysfunction of large AcH interneurons (decreased release)

Describe the Mechanism for Huntington’s disease

Describe Hemiballismus

• What is it?

• Pathophysiology

• Symptoms

• Treatments

Hemiballismus

• What is it?

  • Rare movement disorder

• Pathophysiology:

  • lesion in subthalamic nucleus

    • Cause:

      • Most common = stroke

      • Trauma, tumor, infection, HIV/AIDS

• Symptoms:

  • involuntary flinging movement of the extremities

  • violent movements of the contralateral limb

  • reduced postural reflexes

• Treatments:

  • Dopamine blockers (anti-psychotics) to reduce activity of direct pathway

  • Lesion or deep brain stimulation in globus pallidus

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NOTE: Mech for next Card:

• Activity is decreased in Gpi/SNpr (decreased activation of GPI by indirect pathway & increased inhibition of GPI by direct pathway) and increased activity in thalamus-cortex & PPTN causing violent movements of the contralateral limb (& reduced postural reflexes)

Explain the mech. of Hemiballismus