Transcript Slide 1

First glimpse into A11 function during natural behavior
Release of spinal dopamine in
naturally behaving animals
DA  during REM sleep
dopamine
Wake nREM REM
AW
Hypothalamic dopaminergic drive is inhibited at a time when
sensory (and motor) activity is preferentially depressed
Taepavarapruk et al, 2008
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Dysfunction in DA signaling may reconfigure spinal neural
networks into aberrant behavioral ‘states’
Lower DA
levels:
Higher
affinity
receptors
selectively
activated
Higher DA
levels:
Lower
affinity
receptors
also
activated
Excessive
DA
outcompete inhibitory
actions
sensory,  motor
No DA
loss of inhibitory
tone
sensory,  motor
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Conclusions
The hypothalamic A11 region is the dominant DA projection system to
spinal cord, and projects to sensory, motor and autonomic regions
DA activity in hypothalamus has a circadian pattern
Circadian DA release could rhythmically alter spinal cord dopamine
modulatory properties
All dopamine receptors are expressed in spinal neurons
DA modulates the sensory system
Inhibits nociceptive input and reflexes, may facilitate other inputs
Diurnal DA synthesis pattern onto sympathetics
DA actions are largely inhibitory
Excess sympathetic activity may aberrantly active muscle nociceptors
DA activates the spinal locomotor system
Could an excess or deficient DA system
lead to an RLS-like phenotype?
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Stefan Clemens, PhD
Jorge Quevedo
(CINVESTAV)
Mike Sawchuk
Hong Zhu
Sandra Garraway
NIH (NS045248)
RLS Foundation
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Circuitry
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Architecture
sensory
motor
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DA acts directly on DRG neurons
B
a
C
Dopamine response
spike shape
A
Molokanova & Tamarova, 1995
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