Spinal alpha-motoneurons (""""""""the final common path"""""""") translate a large, complex inflow of synaptic signald from segmentsl and descending fibers and interneurons into a precise output neecessary to maintain posture and initiate movement. In particular motoneurons must intergate information from both """"""""fast"""""""" trasmitters and """"""""slow"""""""" tansmittrs, such as monoamines and peptides which use several different transduction mechanisms (""""""""second messengers"""""""") to influence motoneuron excitability. The process is even more complicated becaues """"""""slow"""""""" transmitters appear able to modulate the effects of """"""""fast"""""""" transmitters. The overall objective of the present investigations is to elucidate some of the complex, interconnected mechanisms by which motoneurons are affected by transmitters putatively released by descending and segmental sources. If dysfunction of synaptic mechanism contorlling motoneurons occurs one would not expect normal spinal cord function. And indeed, abnormalities of motoneuron funcion are imlicated in teh excessive response to passive movement in spasticity, in the absence of reflexes in spinal shock, in the flexor spasms of paraplegia, and in teh pathogenesis of tetanus. Thus, the proposed investigations pertain not only to an imporant area of neurobiology, but are also relevant to understanding the mechanisms of, and ultimately to adequatnely treat, several pathological problems. In exploring synaptic factors taht influence the properties of motoneurons, intra-and extracellular electrophysiological and pharmacological techniques will be used to manipulate and record from frog spinal motoneurons maintained in vitro. These technoiques will be used to test hypotheses taht he output of the motoneuron is governed by compelx pharmacological processes such as the modulatory actions of monoamines and peptides, that these modualtory processes involve multiple receptors and coupling, transduction, and ionic mechanisms, and that jmonoamines and peptides affect the function of mroe classical amino acid transmitters. it is anticipated taht these effeorts will result in a clearer understanding of some of the factors that detrmine how various neurotransmitter and modulator inputs are converted into motoneuron output.
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