Cerebellar Purkinje cell 'spontaneous' spikes interpretation?
dlburg at umich.edu
Fri May 5 11:07:16 EST 1995
I'm primarily a geneticist/mol.biologist and would like some more
informed opinions from this group on something that has come up in
my research. I am working with a mouse neurological mutant called
motor endplate disease (med). The phenotype is a dominant, early-
onset skeletal muscle atrophy which leads to death by three weeks post-
natal. The primary cause was determined by others to be a progressive
loss of neuromuscular transmission at the motor endplate. There are
also cerebellar Purkinje cell defects that (probably) causes an ataxic,
head-shaking phenotype (although clinicians seem to have about fifty
different terms that they say are more descriptive than 'ataxia').
My question concerns the cerebellar aspects of the disease.
Early electrophysiology on the mutant (1970's) Purkinje cells from
brain sections demonstrated an extreme reduction (in number, not
amplitude), relative to normal, of what were termed 'simple' or
'spontaneous' potentials (spikes), without an apparent effect on the
'complex' potentials that co-occur in the same recordings. There were
no other functional abnormalities reported. My question is about the
role of these 'spontaneous' potentials in wildtype animals. Is
anything known about their function?
Since their absence correlates with ataxia and balance problems, is
it possible that they represent a sort of default stream of messages
to skeletal muscles, and function to maintain a sort of dynamic
equilibrium in terms of muscle activity?
In this case, even in the absence of conscious effort at motor activity
(walking and such) there would be a constant low-level input to skeletal
muscles which is random in the sense that it does not evoke an
observable directional movement by the target, but yet maintains a
sort of 'ready state' that allows the target muscles to respond more
smoothly and controllably. Such dynamic equilibria are well documented
for other physiological systems like blood-pressure maintenance,
osmoregulation, etc., and appear to be a elegant adaptive solution
to controlling complex systems efficiently. Could these 'spontaneous'
cerebellar Purkinje potentials be evidence of a similar mechanism in
Along those lines, would it be theoretically possible to treat
cerebellar ataxia arising from defects in maintaining such an
equilibria by utilizing some sort of peripheral nerve 'pacemaker' of
sorts? Does any of this sound reasonable, or am I just another naive
molecular biologist type who has wandered too far from his field?
Thanks in advance for any feedback,
Dept. of Human Genetics
University of Michigan
dlburg at umich.edu
Positional cloning...it's not the kill, it's the thrill of the chase.
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