I was wondering if someone could help me better understand how PD impacts the neurotransmitters and parts of the brain. I understand when the Substantia Nigra is acting normal it behaves as follows…
> The motor cortex sends glutamate (+++) to the Striatum and the Substantia Nigra releases dopamine to the D2 receptors (which are inhibitory) the Striatum (thus inhibiting it in a way)
> Therefore the striatum sends less GABA (-) to the GPE (so it is less inhibited)
> So the GPE releases more GABA (—) to the subthalamic nucleus (inhibiting it)
> Then the subthalamic nucleus releases less glutamate (+) to the GPI
> Since the GPI is not as stimulated it releases less GABA (-) to the Thalamus
> As the Thalamus is less inhibited it releases more Glutamate (++++) to the Motor cortex resulting in more movement
Here is where I get stuck with this system when PD gets involved…
> The motor cortex sends glutamate (+++) to the Striatum and the Substantia Nigra releases less dopamine to the D2 receptors (due to PD )to the Striatum (so it is less inhibiting)
> Since the Striatum is less inhibited it should hypothetically release more GABA (++++) to the GPE thereby inhibiting it
>But if the GPE is more inhibited wouldn’t it release less Gaba to the Subthalamic Nucleus ?
I would greatly appreciate it if anyone can help. I have rewatched the lecture and watched multiple videos on YouTube and I am still confused.
Just filling in the rest of your PD flow:
> The motor cortex sends glutamate (+++) to the Striatum and the Substantia Nigra releases less dopamine to the D2 receptors (due to PD )to the Striatum (so it is less inhibiting)
> Since the Striatum is less inhibited it should hypothetically release more GABA (++++) to the GPE thereby inhibiting it
>But if the GPE is more inhibited wouldn’t it release less Gaba to the Subthalamic Nucleus ?
Yes.
>The GPe releases less GABA, so the STN is less inhibited.
>The STN then releases relatively more glutamate to excite the GPi.
>The GPi then releases more GABA to inhibit the thalamus.
>The thalamus therefore releases less glutamate to the motor cortex, resulting in less movement.