ACh in Parkinson's

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So I've tried to look this up in previous threads, and there really doesn't seem to be a direct answer. Could someone explain to me why ACh is increased in Parkinson's disease? I understand the DA pathways pretty well, but ACh still seems tough to get a hold of here. It is simply that ACh from the cortex is stimulating the striatum, and thus increased ACh stimulation of the striatum without the modulating effects of DA become a greater problem?

Any help would be greatly appreciated. Thanks so much everyone.

 

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Any possible thoughts here for those that may have missed this? Thanks so much for your time.

 

[Transposony]

Basal ganglia controls initiation of movement which is all about the balance between Dopamine and Ach.
Dopamine stimulates Direct pathway via D1 (On switch)
Dopamine also inhibits Indirect pathway via D2 (Off switch)
Ach stimulates Indirect pathway via M3 (Gq) (Off switch)

Normally the movement is initiated since Dopamine is not only stimulating the Direct pathway but it is also inhibiting Indirect pathway simultaneously (inhibits the inhibitor), thereby canceling the stimulation of indirect pathway by Ach.

In PD there is decreased Direct pathway activation and decreased Indirect pathway inhibition by Dopamine.
This leaves Ach unopposed to stimulate Indirect pathway.
So, Ach is not increased per se but it has the major effect (stimulates the inhibition of movement) due to decreased Dopamine.
Hence the use of anticholinergics in PD.

 

[stop2stop]

Basal ganglia controls initiation of movement which is all about the balance between Dopamine and Ach.
Dopamine stimulates Direct pathway via D1 (On switch)
Dopamine also inhibits Indirect pathway via D2 (Off switch)
Ach stimulates Indirect pathway via M3 (Gq) (Off switch)

Normally the movement is initiated since Dopamine is not only stimulating the Direct pathway but it is also inhibiting Indirect pathway simultaneously (inhibits the inhibitor), thereby canceling the stimulation of indirect pathway by Ach.

In PD there is decreased Direct pathway activation and decreased Indirect pathway inhibition by Dopamine.
This leaves Ach unopposed to stimulate Indirect pathway.
So, Ach is not increased per se but it has the major effect (stimulates the inhibition of movement) due to decreased Dopamine.
Hence the use of anticholinergics in PD.

I see, thanks so much for the response. I think what I was missing here was the M3 trigger on the indirect pathways. Makes a ton of sense now, thanks again.

 

[narage]

Basal ganglia controls initiation of movement which is all about the balance between Dopamine and Ach.
Dopamine stimulates Direct pathway via D1 (On switch)
Dopamine also inhibits Indirect pathway via D2 (Off switch)
Ach stimulates Indirect pathway via M3 (Gq) (Off switch)

Normally the movement is initiated since Dopamine is not only stimulating the Direct pathway but it is also inhibiting Indirect pathway simultaneously (inhibits the inhibitor), thereby canceling the stimulation of indirect pathway by Ach.

In PD there is decreased Direct pathway activation and decreased Indirect pathway inhibition by Dopamine.
This leaves Ach unopposed to stimulate Indirect pathway.
So, Ach is not increased per se but it has the major effect (stimulates the inhibition of movement) due to decreased Dopamine.
Hence the use of anticholinergics in PD.

I am actually also curious about this question and have a question regarding this response = I was under the impression the basal ganglia used glutamate as the excitatory NT, not Ach... so I can't understand why you would have increased Ach action during parkinsons.

From my understand... in parkinsons you would have degeneration of substantia nigra. so less Dopamine. So in direct pathway you would not have D1 receptors getting excited and would have less inhibition of globus palidus internum so you would have more inhibition on the thalamus. And in the indirect pathway you would not have D2 receptors excitation to turn off indirect pathway...

..so I still don't see where the Ach comes in to play.

Thank you in advance for any clarification you can provide.