Motor systems II Basal - PowerPoint Presentation

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Motor

systems II

Basal

Ganglia circuitry and motor function

Michael Beierlein, PhD

Department of Neurobiology and Anatomy, MSE R442

McGovern Medical School

Houston, TX

Email: michael.beierlein@uth.tmc.edu

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Functions of the Basal Ganglia

Motor:

gate the initiation of voluntary, behaviorally relevant movements

suppress inappropriate, conflicting movements

control of eye movements

Cognitive:

enabling various cognitive, executive, or emotional programs

learning

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Basal Ganglia Nomenclature

Lenticular

nucleus

Nucleus

accumbens

Caudate

PutamenGlobus pallidusSubthalamic nucleusSubstantia nigra pars compacta (

Ventral Tegmental Area)Substantia nigra pars reticulataStriatum or Neostriatum

Corpus striatum

Neurons are GABAergicNeurons are GlutamatergicNeurons are Dopaminergic

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Basal ganglia neuronal circuits

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The striatum (Caudate, Putamen, nucleus

accumbens

) is the recipient zone of BG afferents

Inputs come from:

Cerebral cortex

Intralaminar

thalamic nuclei (Centromedian nucleus)

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Basal ganglia outputs

globus

pallidus internal segment:

to VA/VL thalamic nuclei

substantia

nigra

pars reticulata: to VA/VL and superior colliculus

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Basal ganglia loops – motor and non-motor

Motor loop

Prefrontal loop

(Associative)

Limbic loop

(Nucleus

accumbens

)

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Lateral view

Medial view

Regions of cortical input to the basal ganglia (blue)

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Basal ganglia outputs are inhibitory

globus

pallidus internal segment:

to VA/VL thalamic nuclei

substantia

nigra

pars reticulata: to VA/VL and superior colliculus

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Output neurons of the basal ganglia (GP and

SNr

) are GABAergic and

have high firing rates, in the absence of synaptic input (

tonic activity

)

GPi neuronal firing(Monkey, in vivo)GPi neuronal firing(mouse, in vitro)

Action potentials

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Basal ganglia outputs

tonically

inhibit their targets

globus

pallidus internal segment ->

inhibits VA/VL thalamic nuclei

substantia nigra pars reticulata -> inhibits VA/VL and superior colliculus

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Direct pathway: - Leads to thalamic disinhibition

-> activation of appropriate motor program

Structures involved:

Cortex - striatum –

GPi

/

SNr – VA/VL thalamus - cortex

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Cortex

VA/VL

GPi

/

SNr

Striatum

Modified from Wichmann and Delong,

Curr Opin Neurobiol. 6:751-758, 1996.

*

*

tonically active

~100 Hz

GPe

STN

*

Direct pathway

Excitation (glutamate)

Inhibition (GABA)

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Direct pathway

Brain stem/

Spinal cord

VA/VL

Striatum

Modified from Wichmann and Delong,

Curr Opin Neurobiol. 6:751-758, 1996.

Direct pathway:

facilitates

movement

*

*

tonically active

~100 Hz

GPe

STN

*

Disinhibition

Cortex

GPi

/

SNr

Excitation (glutamate)

Inhibition (GABA)

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Information flow via dis-inhibitory circuits

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Indirect pathway: - Leads to thalamic inhibition

Structures involved: Cortex – striatum –

GPe

– STN –

Gpi

/

SNr – VA/VL thalamus - cortex-> inhibition of inappropriate motor programs

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Disinhibition

VA/VL

Striatum

*

*

tonically active

~100 Hz

STN

*

Indirect pathway:

inhibits

movement

Cortex

Indirect pathway

GPe

GPi/SNr

Excitation (glutamate)

Inhibition (GABA)

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Center–surround functional

organization of

the direct and

indirect pathways

.

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Basal ganglia outputs

globus

pallidus internal segment:

to VA/VL thalamic nuclei

substantia

nigra

pars reticulata: to VA/VL and superior colliculus

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Control of eye movements via disinhibition of the superior colliculus

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Cortex (FEF)

SC

SNr

Striatum

*

*

tonically active

~100 Hz

GPe

STN

*

Control of eye movements via the basal ganglia

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Striatum

*

*

tonically active

~100 Hz

GPe

STN

*

Disinhibition

Cortex (FEF)

SNr

SC

Control of eye movements via the basal ganglia

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The basal ganglia are important for the generation of

learned motor

sequences/habits

Monkey is rewarded by visually scanning over a “bated” target (one random green target out of a possible 9)

Over many sessions monkey develops patterns of visual scanning that leads to a reward with minimal costs (number of saccades through all targets)

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Firing rate (FR) of striatal neurons over multiple sessions shows that neurons become precisely tuned to start and termination of trained saccade movements

The basal ganglia are important for the generation of

learned motor

sequences/habits

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Dopaminergic projection from

SNc

to striatum

- modulation of indirect and direct pathway

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Cortex

VA/VL

GPi

Striatum

Direct pathway:

facilitates

movement

*

*

tonically

active

~100 Hz

GPe

STN

*

Indirect pathway:

inhibits

movement

D

1

D

2

SNc

The nigrostriatal pathway excites the direct & inhibits the indirect pathway

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Unexpected rewards lead to activation of DA

neurons in the

SNc

and

VTA

-> Direct pathways associated with particular motor programs active during DA release might be strengthened through plastic changes,

possibly leading to a more likely selection of these motor programs in the futureVTAVTAVTA

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Hypokinetic disorders (e.g. Parkinson’s disease)

insufficient direct

pathway output

excess indirect

pathway output

Hyperkinetic disorders (Huntington’s disease,

Hemiballismus

)excess direct pathway

output

insufficient indirect pathway output

Motor behavior is determined by the balance between direct/indirect striatal outputs

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Parkinson’s disease – loss of dopaminergic inputs from

SNc

increased activity in indirect pathway

decreased activity in direct pathway

-> Strong inhibition of motor thalamus, no activation of cortex

VA/VL

GPi

Striatum

Direct pathway:

facilitates

movement

GPe

STN

*

Indirect pathway:

inhibits

movement

D

1

D

2

SNc

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Parkinson’s disease

characterized by slowness or absence of movement (

bradykinesia

or

akinesia

)

Patients have difficulty initiating movements, and once initiated the movements are abnormally slowDeep-brain “stimulation” of the subthalamic nucleus (likely inhibiting the STN), GPi pallidotomy or subthalamotomy can be effective treatments of PD

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Huntington’s disease – loss of striatal neurons of the indirect pathway

decreased activity in indirect pathway

-> Less inhibition of motor thalamus, random activation of cortex

VA/VL

Striatum

Direct pathway:

facilitates

movement

GPe

STN

*

Indirect pathway:

inhibits

movement

D

1

D

2

SNc

GPi

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Huntington’s disease

characterized by

choreiform

movements

: involuntary, continuous movement of the body, especially of the extremities and face.

movements resemble pieces of adaptive movements, but they occur involuntarily and without behavioral significance

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Damage to the STN

->

Hemiballismus

VA/VL

GPi

Striatum

Direct pathway:

facilitates

movement

GPe

STN

*

Indirect pathway:

inhibits

movement

D

1

D

2

SNc

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Hemiballismus

Damage (unilateral) to the sub-thalamic nucleus, often by a stroke

Ballismus

on

contralateral

side of the body

Flailing movements of one arm and legPossible treatments- Dopamine blockers - why could this be effective??

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Reading

:

Neuroscience online

https

://

nba.uth.tmc.edu/neuroscience/s3/chapter04.html

Purves Chapter 18, Modulation of Movement by the Basal Ganglia