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motor lectures

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basal-ganglia.md
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## Modulation of movement by the basal ganglia
<div style="font-size:0.7em">
<div style="font-size:0.8em">
<div></div>
* Basal ganglia are a large set of nuclei that lie deep within the cerebral hemispheres
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Note:
TODO: human brain section from MSU?
Main inputs: Striatum– caudate and putamen
Main outputs of basal ganglia system include: Globus pallidus interna (thalamus) and substantia nigra pars reticulata (superior colliculus, eye movements)
Intermediate nuclei in the basal ganglia system: Globus pallidus externa, STN, and substantia nigra pars compacta
TODO: human brain section
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## Striatum: medium spiny neurons
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TODO:
Kreitzer Ann Rev Neurosci 2009
[lower spine image: http://en.wikipedia.org/wiki/Image:Spines.jpg](http://en.wikipedia.org/wiki/Image:Spines.jpg)
*Inputs from cortical, thalamic, and brainstem structures?*
Medium spiny neuron in the corpus striatum
TODO: mine or other image
TODO: new image
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## Organization of inputs to basal ganglia
<figure><img src="figs/Neuroscience5e-Fig-18.02-0_657b218.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 18.2</figcaption></figure>
<figure><img src="figs/Neuroscience5e-Fig-18.02-0_657b218.jpg" height="450px"><figcaption>Neuroscience 5e Fig. 18.2</figcaption></figure>
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## Projections from MSNs
<div style="font-size:0.9em">
<div></div>
* MSNs of caudate and putamen give rise to inhibitory GABAergic projections that terminate in a pair of nuclei within the basal ganglia called the globus pallidus (GP) and a region of the substantia nigra called the pars reticulata (SNr)
* Approximately 100 MSNs converge onto each neuron in the globus pallidus
* Globus pallidus contains two nuclei– GP externa (GPe) and GP interna (GPi)
* The GPi and the SNr contain the main output neurons of the basal ganglia
* Globus pallidus interna (GPi) neurons then convey information back to the cortex via the thalamus (ventral lateral and ventral anterior nuclei, VA/VL) to make a loop
</div>
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## The direct pathway
<div style="font-size:0.8em">
<div></div>
* Substantia nigra pars reticulata (SNr) neurons project to upper motor neurons in the superior colliculus that command eye movements without going to the thalamus
* **Globus pallidus and pars reticulata neurons are GABAergic**. Unlike MSNs they have high levels of spontaneous activity– they are tonically active
* Thus the output from the basal ganglia is normally inhibitory-- tonic inhibition
* When MSNs fire (in anticipation of movement) this inhibits the inhibition (**disinhibition**) and allows upper motor neurons to send commands to local circuit and lower motor neurons that initiate movement
* Called the direct pathway
</div>
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---
## Basal ganglia disinhibition and the initiation of movement commands in upper motor neurons
## Basal ganglia disinhibition and the initiation of movement
<figure><figcaption class="big">Histograms of spike frequency in
caudate, SNr, SC during eye movements
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Note:
Recall that the superior colliculus contains upper motor neurons concerned with eye movements
[http://www.youtube.com/watch?v=P6uTlnyNaTs](http://www.youtube.com/watch?v=P6uTlnyNaTs)
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## Indirect pathway
<figure><figcaption class="big">Indirect pathway: ctx --> putamen --> GPe --> STN --> GPi --> VA/VL --> ctx</figcaption><img src="figs/2016-11-21-basal-ganglia-circuits_86a5b8d.svg" height="400px"><figcaption>J. Ackman [CC0](https://creativecommons.org/share-your-work/public-domain/cc0/)</figcaption></figure>
<figure><figcaption class="big">Indirect pathway: ctx --> putamen --> GPe --> STN --> GPi --> VA/VL --> ctx</figcaption><img src="figs/2016-11-21-basal-ganglia-circuits_86a5b8d.svg" height="400px"><figcaption>JA [CC0](https://creativecommons.org/share-your-work/public-domain/cc0/)</figcaption></figure>
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## Hemiballismus: violent involuntary movements of the limbs
Defects in the subthalamic nucleus contralateral to the involuntary movements. Reduced indirect pathway function.
<figure><img src="figs/2016-11-21-basal-ganglia-circuits-disease_4509692.svg" height="400px"><figcaption>J. Ackman [CC0](https://creativecommons.org/share-your-work/public-domain/cc0/)</figcaption></figure>
<figure><figcaption class="big">
Defects in the subthalamic nucleus contralateral to the involuntary movements.
Reduced indirect pathway function.
</figcaption><img src="figs/2016-11-21-basal-ganglia-circuits-disease_4509692.svg" height="400px"><figcaption>JA [CC0](https://creativecommons.org/share-your-work/public-domain/cc0/)</figcaption></figure>
Note:
damage to STN results in violent involuntary movements of the limbs.
rarer than Parkinson's (500x less common).
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## Parkinson’s disease
<div style="font-size:0.8em">
<div></div>
* Due to the degeneration of dopaminergic neurons of the substantia nigra pars compacta
* Leads to tremors, slowness of movements, rigidity of extremities and neck, minimal facial expressions
* Slowly progressing disease
* Some success in slowing the progression comes from the use of Levadopa (L-DOPA)– gets converted to dopamine and gets to dopamine receptors in basal ganglia
</div>
<figure><img src="figs/Neuroscience5e-Fig-18.09-1R_ad96451.jpg" height="200px"><figcaption>Neuroscience 5e Fig. 18.9</figcaption></figure>
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## Treatments for Parkinson’s
<div style="width:600px;float:left">
<div></div>
* Dopamine can’t cross the blood brain barrier but L-DOPA can
* Deep brain stimulation
* Cell replacement therapy– implant dopamine making neurons into the striatum
<figure><img src="figs/Neuroscience5e-Fig-06.10-0_d620c90.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 6.10</figcaption></figure>
</div>
<figure style="width:300px;float:left;margin:0 20px"><img src="figs/Neuroscience5e-Fig-06.10-0_d620c90.jpg" height="450px"><figcaption>Neuroscience 5e Fig. 6.10</figcaption></figure>
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* if disease begins in childhood rigidity, seizures, dementia, and rapid progressive course can ensue
* atrophy of striatum is pronounced. Some associated degeneration of frontal and temporal cortices
Function of huntingtin gene product unclear. [Null expression in mice lethal](https://doi.org/10.1016%2F0092-8674%2895%2990542-1)
upregulates brain derived neurotrophic factor (BDNF). evidence that [huntingtin interacts with 19 different proteins](https://doi.org/10.1016%2FS0968-0004%2803%2900168-3)
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## Huntington’s disease
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Note:
15-34 CAG DNA repeats normally, 42-66 in Huntingtin's disease resulting in an unstable triplet repeat in coding region of gene. Polyglutamine
15-34 cytosine-adenine-guanine (CAG) DNA repeats normally, 42-66 in Huntingtin's disease resulting in an unstable triplet repeat in coding region of gene. Polyglutamine
--
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## Non-motor loops of the basal ganglia
* Basal ganglia are also involved in loops that modulate non-motor behaviors
* Maybe work the same way to suppress outputs
* A limbic loop that may regulate emotional behavior and motivation
* Work in a similar way to suppress outputs
* The limbic loop regulates emotional behavior and motivation
* Tourette’s may be a problem with limbic loop (no longer have inhibitions about language?)
* Drugs of abuse affect dopamine release
* Schizophrenia, may be due to aberrant activity in limbic and prefrontal loops resulting in hallucinations disordered cognition
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Tourettes may be a disruption to non-motor corticostriatal loops.
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