question about parkinson's desease - rotation direction?

Dallas Grasby dallas.grasby at adelaide.edu.au
Tue Jan 16 20:30:51 EST 2001



Shamim Khaliq wrote:

> drew a picture too!
>
> Theophilus Samuels <theophilus.samuels at btinternet.com> wrote
> >   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
>
>  [Image]

This thread on activity in the pars compacta of the substantia nigra makes it
clear that dopaminergic degeneration in this nucleus results in a decreased
excitation of the cortex by the thalamus.  What explanations are offered for
the rotation exhibited by rats with unilateral lesions of the substantia
nigra?  ie dopamine release in the innervated striatum after amphetamine
exposure results in rotation TOWARDS the lesion, while activation of
supersensitive receptors in the denervated striatum via dopamine agonists like
apomorphine results in rotation in the opposite direction.  Considering that
much of the activity in these pathways will influence motor ouput to the
opposite side of the body, the asymmetric activation of the striata must have
complex outcomes so as to produce the rotation.  The first 'guess' with this
rotation model is that the dominant striatum will "drive" activty in the
contralateral limbs creating a rotation away from the lesion - but of course
the opposite is true.  What is the best explanation?  Any good reviews/papers
on this mechanism?

thanks,

--
Dr Dallas Grasby PhD

Group Leader
Preclinical Studies
Cell Therapy Program
BresaGen Pty Ltd

Postal Address:

Dr Dallas Grasby
Discipline of Biochemistry
Department of Molecular Biosciences
University of Adelaide
Adelaide, 5005
South Australia
Australia

Tel: +61-8-8303-4623
Fax: +61-8-8303-4348

dallas.grasby at adelaide.edu.au







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