diff --git a/basal-ganglia.md b/basal-ganglia.md index 27fc029..54ed6b4 100644 --- a/basal-ganglia.md +++ b/basal-ganglia.md @@ -1,6 +1,6 @@ ## Modulation of movement by the basal ganglia -
+
* Basal ganglia are a large set of nuclei that lie deep within the cerebral hemispheres @@ -95,14 +95,14 @@ Note: 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 + --- ## Striatum: medium spiny neurons @@ -117,17 +117,15 @@ Intermediate nuclei in the basal ganglia system: Globus pallidus externa, STN, a Note: -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 --- @@ -145,7 +143,7 @@ Note: ## Organization of inputs to basal ganglia -
Neuroscience 5e Fig. 18.2
+
Neuroscience 5e Fig. 18.2
Note: @@ -164,12 +162,17 @@ Note: ## Projections from MSNs +
+
+ * 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 +
+ Note: @@ -188,12 +191,17 @@ Note: ## The direct pathway +
+
+ * 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 +
+ 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
Histograms of spike frequency in caudate, SNr, SC during eye movements @@ -231,6 +239,8 @@ caudate, SNr, SC during eye movements 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) @@ -262,7 +272,7 @@ Note: ## Indirect pathway -
Indirect pathway: ctx --> putamen --> GPe --> STN --> GPi --> VA/VL --> ctx
J. Ackman [CC0](https://creativecommons.org/share-your-work/public-domain/cc0/)
+
Indirect pathway: ctx --> putamen --> GPe --> STN --> GPi --> VA/VL --> ctx
JA [CC0](https://creativecommons.org/share-your-work/public-domain/cc0/)
Note: @@ -385,24 +395,32 @@ Note: ## Hemiballismus: violent involuntary movements of the limbs -Defects in the subthalamic nucleus contralateral to the involuntary movements. Reduced indirect pathway function. - -
J. Ackman [CC0](https://creativecommons.org/share-your-work/public-domain/cc0/)
+
+Defects in the subthalamic nucleus contralateral to the involuntary movements. +Reduced indirect pathway function. +
JA [CC0](https://creativecommons.org/share-your-work/public-domain/cc0/)
Note: damage to STN results in violent involuntary movements of the limbs. +rarer than Parkinson's (500x less common). + --- ## Parkinson’s disease +
+
+ * 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 +
+
Neuroscience 5e Fig. 18.9
@@ -492,11 +510,16 @@ alzheimers: ## Treatments for Parkinson’s +
+
+ * 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 -
Neuroscience 5e Fig. 6.10
+
+ +
Neuroscience 5e Fig. 6.10
Note: @@ -536,6 +559,12 @@ Note: * 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) + + + -- ## Huntington’s disease @@ -547,7 +576,7 @@ 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 -- @@ -596,8 +625,8 @@ https://www.youtube.com/watch?v=OjM9Gl_MLyQ ## 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 @@ -642,5 +671,3 @@ https://www.youtube.com/watch?v=OjM9Gl_MLyQ Note: Tourettes may be a disruption to non-motor corticostriatal loops. - ---- diff --git a/motor1.md b/motor1.md index 44a6625..6c39d63 100644 --- a/motor1.md +++ b/motor1.md @@ -452,7 +452,7 @@ Note: But the infrafusal muscle fibers are muscle-- why not just have the muscle spindle feedback and be done with it... -Need to adjust the muscle spindles so that they can provide useful feedbac across a range of muscle lengths. +Need to adjust the muscle spindles so that they can provide useful feedback across a range of muscle lengths. Provide gain to keep muscle spindles active at all lengths. Think about your big guns you use to hold that glass of oktoberfest... changing length of biceps @@ -488,7 +488,7 @@ Note: * Encapsulated afferent nerve endings located at the junction of the muscle and tendon * Each tendon is innervated by a single sensory group Ib sensory axon * Unlike spindle fibers, golgi tendon organs fire when muscle contracts -* Ib axons from Golgi tendon organs contact inhibitory local circuit neurons in the spinal cord (Ib inhibitory neurons) that synapse with the α motor neurons that innervate the same muscle +* Ib axons from Golgi tendon organs contact inhibitory local circuit neurons in the spinal cord (Ib inhibitory neurons) that synapse with the α motor neurons that innervate the same muscle * Helps prevent fatigue
@@ -563,7 +563,7 @@ V2 Glutamatergic V2a and Inhibitory V2b Ipsilaterally and caudally V3 Excitatory Commissural Caudally -Goulding M (July 2009). "Circuits controlling vertebrate locomotion: moving in a new direction". Nature Reviews. Neuroscience. 10 (7): 507–18. doi:10.1038/nrn2608. PMC 2847453free to read. PMID 19543221. +Goulding M (July 2009). "Circuits controlling vertebrate locomotion: moving in a new direction". Nature Reviews Neuroscience. 10 (7): 507–18. doi:10.1038/nrn2608. PMC 2847453 PMID 19543221. --- diff --git a/motor2.md b/motor2.md index d78b369..4ca3e38 100644 --- a/motor2.md +++ b/motor2.md @@ -481,10 +481,14 @@ Summing response from a bunch of neurons shows that the direction is better enco ## Controlling a robotic arm using motor cortex activity patterns in real time -
Monkey brain machine interface
+
Monkey brain machine interface
+ Note: + +[TED talk by Miguel Nicolelis](https://youtu.be/CR_LBcZg_84) +