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EFFECTIVE SYNAPTIC CURRENTS IN MOTONEURONS

EFFECTIVE SYNAPTIC CURRENTS IN MOTONEURONS
运动神经元中的有效突触电流
批准号:
2609617
负责人:
MARC D BINDER
金额:
$12.52万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1988
资助国家:
美国
项目状态:
已结题
起止时间:
1988-12-01 至 1999-11-30

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中文摘要
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英文摘要
The long-term objective of the research conducted in this laboratory is to understand the functional organization of mammalian motoneuron pools. Of particular interest is the distribution of synaptic inputs from segmental and descending systems to motoneurons and their roles in shaping motor output from the spinal cord. The approach taken is a synthetic one, combining computer modelling and simulation studies with electrophysiological measurements in cat spinal motoneurons. In this renewal application, there are three specific aims. The first specific aim is to continue studies on how effective synaptic currents from different input systems are distributed to the constituent members of both flexor and extensor motoneuron pools. A modified, voltage clamp technique will be used in these studies to measure the amount of current that reaches the soma and initial segment of a motoneuron under steady- state conditions. This quantity is referred to as the effective synaptic current (IN) because only that fraction of a synaptic current that actually reaches the soma and initial segment of the motoneuron directly affects its recruitment and firing frequency. The synaptic input systems that will be studied are a low threshold, cutaneous pathway, an ipsilateral flexor reflex afferent (FRA) pathway, the corticospinal, the rubrospinal and the lateral vestibulospinal pathways. The second specific aim is to study how different descending and segmental synaptic systems interact when they are activated concurrently. In each of the experiments, one descending system (corticospinal, rubrospinal or vestibulospinal) will be prepared for stimulation along with as many as five different segmental inputs (Ia excitation, Ia inhibition, Renshaw inhibition, low-threshold cutaneous, and FRA). Comparisons will be made of the effective synaptic currents generated by each input in isolation with the net effective synaptic currents produced when two or more inputs are activated together. In addition, the effects of the individual and combined inputs on the rate of motoneuron discharge will also be assessed in these experiments by activating the synaptic inputs while the motoneurons are discharging in response to current pulses injected through the recording microelectrode. The third specific aim is to test the hypothesis that under steady-state conditions, the transformation of synaptic inputs by motoneurons into spike discharge frequency can be described simply as the product of the net effective synaptic current they receive and the slope of their frequency-current relations within the primary range of firing. In these experiments, the frequency-current relation of a motoneuron will be measured, as well as the effective synaptic currents generated in it by one or more inputs. Subsequently, the same synaptic inputs will be added to the injected currents and the observed change in firing rate will be compared to that predicted based on the magnitude of the effective synaptic current and the slope of the frequency-current relation.
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Motoneuron mortality in neurodegenerative diseases induced by homeostatic dysregulation of excitability
Motoneuron mortality in neurodegenerative diseases induced by homeostatic dysregulation of excitability
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  • 项目类别:
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