Journal
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
Volume 27, Issue 1-2, Pages 120-125Publisher
WILEY
DOI: 10.1046/j.1440-1681.2000.03202.x
Keywords
ATP; development; excitability; hypoglossal; motoneuron; mouse; noradrenaline; phrenic; rat
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1. Motoneurons (MN) shape motor patterns by transforming inputs into action potential output, This transformation, excitability, is determined by an interaction between synaptic inputs and intrinsic membrane properties. Excitability is not static, but changes over multiple time scales. The purpose of the present paper is to review our recent data on synaptic factors important in the dynamic control of MN excitability over time scales ranging from weeks to milliseconds. 2. Developmental changes in modulation of MN excitability are well established. Noradrenergic potentiation of hypoglossal (XII) MN inspiratory activity in rhythmically active medullary slice preparations from rodents increases during the first two postnatal weeks. This is due to increasing alpha(1)- and beta-adrenoceptor excitatory mechanisms and to a decreasing inhibitory mechanism mediated by alpha(2)-adrenoceptors. Over a similar period, ATP potentiation of XII inspiratory activity does not change. 3. Motoneuron excitability may also change on a faster time scale, such as between different behaviours or different phases of a behaviour. Examination of this has been confounded by the fact that excitatory synaptic drives underlying behaviour can obscure smaller concurrent changes in excitability. Using the rhythmically active neonatal rat brain-stem-spinal cord preparation, we blocked excitatory inspiratory drive to phrenic MN (PMN) to reveal a reduction in PMN excitability specific to the inspiratory phase that: (i) arises from an inhibitory GABAergic input; (ii) is not mediated by recurrent pathways; and (iii) is proportional to and synchronous with the excitatory inspiratory input. We propose that the proportionality of the concurrent inhibitory and excitatory drives provides a means for phase-specific modulation of PMN gain. 4. Modulation across such diverse time scales emphasizes the active role that synaptic factors play in controlling MN excitability and shaping behaviour.
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