Basal Ganglia

So FA Basal Ganglia section is atrocious. Or at least, I feel like their image of the direct/inhibit pathway is poor because it doesn't demonstrate inhibition or excitatory connection or the NT's that are responsible.

Here's what it says for Excitatory pathway (Direct):

"cortical inputs stimulate the striatum, stimulating the release of ACh, which disinhibits the thalamus via the Gpi/SnR."

I thought it worked such that GPi/SNr normally inhibits activation of the thalamus (which first aid states). And that the striatum releases GABA which inhibits the GPiSNR mediated inhibition. Little confused as to where ACh is coming into this picture.

Striatum is definitely GABA-releasing. The striatum is stimulated by the cortex to release GABA. By the indirect pathway, this GABA will hit the GPe. By the direct pathway, the GABA will hit GPi. GPe inhibition leads to inhibition of the subthalamic nucleus, which leads to disinhibition of the GPi and thus inhibition of motion through GPi's suppressive action on the thalamus. GPi inhibition (through the direct pathway) leads to disinhibition of thalamus, allowing motion

Edit: This is a good picture

Originally Posted by loveoforganic

Striatum is definitely GABA-releasing. The striatum is stimulated by the cortex to release GABA. By the indirect pathway, this GABA will hit the GPe. By the direct pathway, the GABA will hit GPi. GPe inhibition leads to inhibition of the subthalamic nucleus, which leads to inhibition of motion. GPi inhibition leads to disinhibition of thalamus, allowing motion

Edit: This is a good picture

Right this is what I remember. I'm just need sure where ACh is coming into the picture.

It's either an error, or it was completely neglected from any of my basal ganglia lectures

Originally Posted by mdeast

Right this is what I remember. I'm just need sure where ACh is coming into the picture.

Striatum has AChergic neurons which activates GABAergic neurons that ultimately project outside of the striatum (the images are just neglecting to show that intermediate step)

Originally Posted by iheartmints

Striatum has AChergic neurons which activates GABAergic neurons that ultimately project outside of the striatum (the images are just neglecting to show that intermediate step)

Interesting, thanks. As a matter of curiosity, would drugs affecting ACh levels have any effect in parkinsons? Or would there be equal stimulation of both pathways?

Originally Posted by loveoforganic

Interesting, thanks. As a matter of curiosity, would drugs affecting ACh levels have any effect in parkinsons? Or would there be equal stimulation of both pathways?

Right on. Tilting the dopamine-ACh axis towards dopamine helps in Parkinson's, no matter how you do it.

Benztropine is an anticholinergic used to treat Parkinson's, especially drug-induced Parkinsonism.

Originally Posted by loveoforganic

Interesting, thanks. As a matter of curiosity, would drugs affecting ACh levels have any effect in parkinsons? Or would there be equal stimulation of both pathways?

Yes because Parkinsons has too much ACh activity and too little DA and you must balance the two

There are 2 types of GABAergic neurons that project out of the striatum, both activated by ACh, but they also have 2 different types of DA receptors that compete with ACh signalling. D1 in excitatory pathway and D2 in inhibitory pathway. Whats the role of DA? Its ultimately excitatory by inhibiting inhibitory pathway and activating excitatory pathway. If you lose DA, now ACh is the only one signalling and you now have bradykinesia. Bradykinesia is not affected by antimuscarinics but you can control the tremors with antimuscarinics from the excess ACh in excitatory pathway or rigidity from too much ACh turning on GABA release in inhibitory pathway