Our findings of uncorrelated activity of neurons in the output
stage of the basal ganglia enable us to suggest a novel
computational model for information processing in the basal ganglia.
Briefly, the model claims that the main axis of the basal ganglia
performs dimensionality (redundancy) reduction of the information
space spanned by the cortical activity. This information compression
is controlled by the modulatory neurotransmitters of the basal
ganglia, e.g., the dopaminergic and cholinergic systems. This is why
we are now trying to get an insight into the physiology of
neurobiological reward systems. Recently, Schultz and co workers
have suggested that dopaminergic neurons in the substantia nigra
pars compacta (SNc) are feature detectors for the degree to which
environmental events are different from predictions. The cholinergic
interneurons of the striatum (the tonically active neurons, TANs)
show similar responses. Both the dopaminergic and cholinergic
systems are affected in Parkinson's disease (the
dopamine-acetylcholine balance hypothesis), and prominent learning
disabilities have been identified in this disorder.
We recorded from both neuronal populations in monkeys performing
a probabilistic instrumental conditioning task. Our results suggest
that despite the aforementioned similarities, the messages carried
by the two systems are functionally distinct. While the response of
the temporally uncorrelated dopamine neurons reflects mismatch
between expectation and outcome, the highly correlated acetylcholine
neurons respond identically to all behaviorally significant events,
regardless of their predictability or rewarding value. We propose
that while the acetylcholine reaction illuminates the timing of
potentially significant events, the dopaminergic signal acts within
this time frame to teach the system in view of those events. The
combined effect of these two signals yields an appropriate
alteration of the strength of cortico-striatal connections.
In parallel, we carried a detailed study of the basal ganglia
activity following dopamine replacement therapy. We have shown that
in the MPTP treated monkeys, dopamine replacement restore the
abnormal uncorrelated activity of pallidal units. We are now
studying the different neuronal behavior (firing rate, pattern and
synchronization) following "optimal" dopamine therapy and during
levo-dopa induced dyskinesia. In parallel, we are studying the
neuronal activity in the substantia nigra pars reticulata (SNr)
following involuntary oro-facial movements (tics). We believe that
these studies will lead to better understanding of the
pathophysiology of these common hyperkinetic disorders. In the near
future we hope to test the hypothesis that in terms of the learning
related function of the basal ganglia, the parkinsonian (dopamine
depleted) state can be characterized as a state in which striatal
neurons receive signals that erroneously indicate that predicted
rewards failed to occur. Finally, the hypothesis will be studied
that (tonic) dopamine replacement therapy improves Parkinsonism in
part by normalizing the reward signals of cholinergic striatal
cells.
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