The basal ganglia, or rather the circuitry of the basal ganglia is rather
complicated; especially when there are so many NTs to contend with. There
are two major pathways of the basal ganglia which must be understood if one
is to comprehend PD. Before beginning any discussion, it is important to
state the components of the basal ganglia - (a) caudate nucleus, (b)
putamen, (c) globus pallidus (internal and external segments), (d)
subthalamic nucleus and (e) substantia nigra of the midbrain (pars
reticulata and compacta). It is also important to remember which NTs are
used and whether they are excitatory or inhibitory. The caudate along with
the putamen, of course makes up the striatum, while the medial aspect of the
globus pallidus and lateral putamen make up the lentiform nucleus.
From here on, I suggest you try to draw out the following. The DIRECT
pathway is the inhibitory striatal projection to the globus pallidus
(internal segment) and substantia nigra pars reticulata (which I think you
were referring to). These two regions then send inhibitory projections to
the thalamus using GABA. The INDIRECT pathway is the inhibitory striatal
projection to the globus pallidus (external segment), which then sends
inhibitory projections to the subthalamic nucleus. The subthalamic nucleus
can send excitatory projections to both of the pallidal segments and the
substantia nigra pars reticulata.
The direct pathway utilises GABA and substance P, both inhibitory NTs.
Basically, in order to move the thalamic cells are released from tonic
inhibition that occurs when corticostriate inputs excite striatal neurons
(don't go further until you understand this inhibition of inhibition
sequence). The removal of inhibition on the thalamic neurons is now thought
to facilitate movement by exciting premotor and supplementary motor areas.
The indirect pathway involves cortical projections excitating and thus
inhibiting the external segment of the globus pallidus, via GABA and
enkephalin, which results in the disinhibition of the subthalamic nucleus,
mediated by GABA, with the resultant increase in stimulation to the globus
pallidus internal segment and substantia nigra pars reticulata. And of
course, this inhibits the thalamus and decreases the excitation of the
supplementary motor area.
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], while it also INHIBITS the INDIRECT
pathway resulting in [again, you work it out]. Dopamine therefore acts to
facilitate both pathways and create an equilibrium between the two which in
turn facilitates movement.
You can now understand that disturbances in the activity of these pathways
can lead to all sorts of problems and indeed this is what occurs in PD. The
loss of dopaminergic input to the striatum results in the decreased
excitation of the direct pathway and decreased inhibition of the indirect
pathway, from this work out what now takes place.
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 a
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 increased
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'
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 has
> 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 and
> 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?