Qester

10+ Year Member
Jul 15, 2007
450
70
Status
  1. Medical Student
Hello everyone,

I am having some confusion about the basal ganglia and movement and was hoping to get some clarification

From my understanding there are two pathways, the direct and indirect.

The Direct Pathway goes as follows
1) The GPi inhibits the thalamus preventing movement
2) The Putamen gets stimulated by the SNc in the direct pathway (D1)
3) The Stimulated Putamen Inhibits the GPi (inhibiting the inhibitor), thus allowing movement
- damage to the direct pathway results in decreased movement, seen in parkinsons

The Indirect Pathway goes as follows
1) The GPi inhibits the thalamus preventing movement
2) The STN stimulates the GPi further preventing movement
3) The GPe inhibits is usually inhibiting the STN so step 2 doesn't happen
4) The Putamen can inhibit the GPe (inhibiting the inhibitor), thus activating the STN, and inhibiting movement via activation of the GPi
5) ***This is where i get confused. The Indirect pathway is done by the D2, which on the Putamen is inhibitory... So I don't understand how If I Inhibit, the inhibitor, of the inhibitor that I get activation of the STN and then the GPi? When I work it out I get inhibition.

Where am I getting messed up.
 

HereWeGo21

5+ Year Member
May 27, 2013
130
73
Status
  1. Medical Student
Not totally following your process. But in Parkinson's, you get loss of the substantia nigra. This, normally, sends both excitatory and inhibitory projections to the putamen. Loss of each one has the same effect, which is to cause an extra-active GPi.

For the indirect pathway, in PD:
  1. Substantia nigra no longer inhibits the Putamen via D2
  2. Putamen projections to the GPe are now MORE active. These are inhibitory projections.
  3. So, the GPe will be LESS active. The GPe normally inhibits the STN.
  4. So, now the STN is LESS inhibited, and MORE active. The STN excites the GPi. Now, it does so even stronger.
  5. The GPi is EXTRA active, and so inhibits the thalamus more.
  6. The thalamus is less active, and so inhibits the cortex more.
This diagram will help. black is inhibitory, white is excitatory.
https://www.unifr.ch/biochem/assets/images/dreyer/research/parkinson/thalamo_cortical_cirtui.jpg
 
  • Like
Reactions: 1 user

Qester

10+ Year Member
Jul 15, 2007
450
70
Status
  1. Medical Student
Not totally following your process. But in Parkinson's, you get loss of the substantia nigra. This, normally, sends both excitatory and inhibitory projections to the putamen. Loss of each one has the same effect, which is to cause an extra-active GPi.

For the indirect pathway, in PD:
  1. Substantia nigra no longer inhibits the Putamen via D2
  2. Putamen projections to the GPe are now MORE active. These are inhibitory projections.
  3. So, the GPe will be LESS active. The GPe normally inhibits the STN.
  4. So, now the STN is LESS inhibited, and MORE active. The STN excites the GPi. Now, it does so even stronger.
  5. The GPi is EXTRA active, and so inhibits the thalamus more.
  6. The thalamus is less active, and so inhibits the cortex more.
This diagram will help. black is inhibitory, white is excitatory.
https://www.unifr.ch/biochem/assets/images/dreyer/research/parkinson/thalamo_cortical_cirtui.jpg

Thanks, that diagram is exactly what I needed, I was thinking of the indirect pathway as more as an all or none phenomenon, rather than a gradient pathway.
 
About the Ads

Qester

10+ Year Member
Jul 15, 2007
450
70
Status
  1. Medical Student
Not totally following your process. But in Parkinson's, you get loss of the substantia nigra. This, normally, sends both excitatory and inhibitory projections to the putamen. Loss of each one has the same effect, which is to cause an extra-active GPi.

For the indirect pathway, in PD:
  1. Substantia nigra no longer inhibits the Putamen via D2
  2. Putamen projections to the GPe are now MORE active. These are inhibitory projections.
  3. So, the GPe will be LESS active. The GPe normally inhibits the STN.
  4. So, now the STN is LESS inhibited, and MORE active. The STN excites the GPi. Now, it does so even stronger.
  5. The GPi is EXTRA active, and so inhibits the thalamus more.
  6. The thalamus is less active, and so inhibits the cortex more.
This diagram will help. black is inhibitory, white is excitatory.
https://www.unifr.ch/biochem/assets/images/dreyer/research/parkinson/thalamo_cortical_cirtui.jpg

I was revisiting this concept, a new question arised, why do we have hyperkinetic movement (pill rolling tremor) in parkinsons if the SNc is absent?
 

HereWeGo21

5+ Year Member
May 27, 2013
130
73
Status
  1. Medical Student
I was revisiting this concept, a new question arised, why do we have hyperkinetic movement (pill rolling tremor) in parkinsons if the SNc is absent?
Not really sure, but I've always thought of PD as "not enough cortical excitation", and so I figured that the descending motor system needs some cortical input to "prevent" the pill rolling tremor. In other words, we have a pill-rolling tremor at baseline, and adequate cortical input allows the motor system to overpower that. If that makes sense. Not really a scientific answer, but yeah in short I agree that it's a bit counterintuitive.

On the other hand, compare what happens if we have too much cortical excitation. This would include Huntington's (writhing, grimacing) and hemiballism. These are a far cry from PD.
 

Qester

10+ Year Member
Jul 15, 2007
450
70
Status
  1. Medical Student
Not really sure, but I've always thought of PD as "not enough cortical excitation", and so I figured that the descending motor system needs some cortical input to "prevent" the pill rolling tremor. In other words, we have a pill-rolling tremor at baseline, and adequate cortical input allows the motor system to overpower that. If that makes sense. Not really a scientific answer, but yeah in short I agree that it's a bit counterintuitive.

On the other hand, compare what happens if we have too much cortical excitation. This would include Huntington's (writhing, grimacing) and hemiballism. These are a far cry from PD.

Ah k interesting... As far as I can recall in class we were taught that a direct pathway injury lead to hypokinesis, an indirect pathway injury lead to hyperkinesis. Essentially all movement disorders (hemiballism, chorea etc..) were indirect pathway damage leading to more movement, however PD affected both pathways having hypo and hyperkinesis.

That process of thinking has done well for me on questions and it made sense if the SNc sent positive input to the Putamen. But since the D2 receptors of the indirect pathway are inhibitory it all fell apart and I am trying to put humpty dumpty back together in my head haha
 
This thread is more than 4 years old.

Your message may be considered spam for the following reasons:

  1. Your new thread title is very short, and likely is unhelpful.
  2. Your reply is very short and likely does not add anything to the thread.
  3. Your reply is very long and likely does not add anything to the thread.
  4. It is very likely that it does not need any further discussion and thus bumping it serves no purpose.
  5. Your message is mostly quotes or spoilers.
  6. Your reply has occurred very quickly after a previous reply and likely does not add anything to the thread.
  7. This thread is locked.
About the Ads