* Basal ganglia are a large set of nuclei that lie deep within the cerebral hemispheres
* Basal ganglia are a large set of nuclei that lie deep within the cerebral hemispheres
@@ -95,14 +95,14 @@ Note:
Note:
Note:
TODO: human brain section from MSU?
Main inputs: Striatum– caudate and putamen
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)
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
Intermediate nuclei in the basal ganglia system: Globus pallidus externa, STN, and substantia nigra pars compacta
TODO: human brain section
---
---
## Striatum: medium spiny neurons
## Striatum: medium spiny neurons
@@ -117,17 +117,15 @@ Intermediate nuclei in the basal ganglia system: Globus pallidus externa, STN, a
*Inputs from cortical, thalamic, and brainstem structures?*
*Inputs from cortical, thalamic, and brainstem structures?*
Medium spiny neuron in the corpus striatum
Medium spiny neuron in the corpus striatum
TODO: mine or other image
TODO: new image
---
---
@@ -145,7 +143,7 @@ Note:
## Organization of inputs to basal ganglia
## 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>
Note:
Note:
@@ -164,12 +162,17 @@ Note:
## Projections from MSNs
## 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)
* 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
* Approximately 100 MSNs converge onto each neuron in the globus pallidus
* Globus pallidus contains two nuclei– GP externa (GPe) and GP interna (GPi)
* 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
* 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
* 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>
Note:
Note:
@@ -188,12 +191,17 @@ Note:
## The direct pathway
## 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
* 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
* **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
* 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
* 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
* Called the direct pathway
</div>
Note:
Note:
@@ -222,7 +230,7 @@ Note:
---
---
## 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
<figure><figcaption class="big">Histograms of spike frequency in
caudate, SNr, SC during eye movements
caudate, SNr, SC during eye movements
@@ -231,6 +239,8 @@ caudate, SNr, SC during eye movements
Note:
Note:
Recall that the superior colliculus contains upper motor neurons concerned with eye movements
damage to STN results in violent involuntary movements of the limbs.
damage to STN results in violent involuntary movements of the limbs.
rarer than Parkinson's (500x less common).
---
---
## Parkinson’s disease
## Parkinson’s disease
<div style="font-size:0.8em">
<div></div>
* Due to the degeneration of dopaminergic neurons of the substantia nigra pars compacta
* 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
* Leads to tremors, slowness of movements, rigidity of extremities and neck, minimal facial expressions
* Slowly progressing disease
* 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
* 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>
<figure><img src="figs/Neuroscience5e-Fig-18.09-1R_ad96451.jpg" height="200px"><figcaption>Neuroscience 5e Fig. 18.9</figcaption></figure>
@@ -492,11 +510,16 @@ alzheimers:
## Treatments for Parkinson’s
## Treatments for Parkinson’s
<div style="width:600px;float:left">
<div></div>
* Dopamine can’t cross the blood brain barrier but L-DOPA can
* Dopamine can’t cross the blood brain barrier but L-DOPA can
* Deep brain stimulation
* Deep brain stimulation
* Cell replacement therapy– implant dopamine making neurons into the striatum
* 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>
Note:
Note:
@@ -536,6 +559,12 @@ Note:
* if disease begins in childhood rigidity, seizures, dementia, and rapid progressive course can ensue
* 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
* 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)
--
--
## Huntington’s disease
## Huntington’s disease
@@ -547,7 +576,7 @@ Note:
Note:
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
## Stimulation of the ‘bitter’ taste cortex is sufficient to make a mouse pucker
## Stimulation of the ‘bitter’ taste cortex is sufficient to make a mouse pucker
<div><img src="figs/ScreenShot2016-02-22at4.43.22PM_712d13b.png" height="400px"><figcaption>[Video 1 from Peng et al., Nature 2015](http://www.nature.com/nature/journal/vaop/ncurrent/fig_tab/nature15763_SV1.html)</figcaption></div>
<div><img src="figs/ScreenShot2016-02-22at4.43.22PM_712d13b.png" height="400px"><figcaption>[Video 1 from Peng et al., Nature 2015](https://www.nature.com/articles/nature15763#supplementary-information)</figcaption></div>
Note:
Note:
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