thank you for that beautifully clear explanation. it'll take some time for
me to predict inhibition of inhibition correctly from looking at pathway
diagrams, but that's a mini-course in of itself. i can, however follow your
Theophilus Samuels <theophilus.samuels at btinternet.com> wrote
> Now, once you have got past all of this essential information, the
> following is fundamental in understanding PD. Projections from the
> substantia nigra pars compacta (the region where dopaminergic cell loss
> occurs in PD) has TWO effects on the striatum depending on whether the
> direct or indirect pathway is involved. Thus, dopamine EXCITES the DIRECT
> pathway resulting in [you work it out],
inhibiting the tonic inhibition of the thalamus from the corticostriate
pathway, thus increasing thalamocortical excitation of the prefrontal and
primary motor areas.
> while it also INHIBITS the INDIRECT
> pathway resulting in [again, you work it out].
thus the globus pallidus externa sends less inhibition to the (tonic?)
corticosubthalamic excitation of the globus pallidus and substantia nigra
pars reticulata, so the globus pallidus interna and substantia nigra pars
reticulata increase their inhibition of the thalamus, and the thalamus
decreases excitation of the prefrontal and primary motor areas.
> Dopamine therefore acts to
> facilitate both pathways and create an equilibrium between the two which
> turn facilitates movement.
> You can now understand that disturbances in the activity of these
> can lead to all sorts of problems and indeed this is what occurs in PD.
> loss of dopaminergic input to the striatum results in the decreased
> excitation of the direct pathway
there's less disinhibition of the thalamus which would have made the
thalamus more excitatory on the cortex, so thalamocortical excitation
> and decreased inhibition of the indirect
> pathway, from this work out what now takes place.
there's less inhibition of the thalamus which would have made thalamus less
excitatory on the cortex, so thalamocortical excitation increases
> This is more of an overview of what takes place but it does serve to
> correct your 'logic' - see below. Also remember that PD pathophysiology is
> lot more complicated, involving degeneration of the raphe nuclei, motor
> nucleus of the vagus nerve and locus ceruleus with reduction in serotonin
> and norepinephrine NT levels.
>> > so exiting the substantia nigra pars compacta has an inhibitory
> > effect on the cerebral motor cortex.
>> This is wrong. As discussed above, stimulation will result in an
> activity of the direct pathway and decreased activity of the indirect
> pathway with resultant increase in the activity of the excitatory thalamic
> projections to the supplementary motor cortex.
>> 'It was worth it in the end'
i hope so. it was for me. how was it for you? (joke, but thanks. i feel
>> Shamim Khaliq <shamimkhaliq at hotmail.com> wrote in message
> news:3a619036$1_4 at news.intensive.net...> > The way I understand it, the substantia nigra pars compacta has a lot of
> > dopaminergic neurons that go to the striatum (caudate and putamen) that
> > a lot of GABAergic neurons that go to the globus pallidus interna that
> > load of GABAergic neuron that go to the thalamus which goes to the motor
> > cortex, so exiting the substantia nigra pars compacta has an inhibitory
> > effect on the cerebral motor cortex. So, if the substantia nigra pars
> > compacta degenerates, as in Parkinson's, the striatum is less excited
> > sends less inhibition to the motor cortex.
> > NOT TRUE! Parkinson's is too much inhibition of the cortex, rigidity and
> > slowness of movement, not too much movement (as is caused by giving them
> > levodopa). So somehow, killing the dopaminergic projections from the
> > substantia nigra pars compacta to the striatum must INCREASE striatal
> > inhibition of the motor cortex. Where is my logic failing me?