SENSORY RECALIBRATION OF MOTOR OUTPUT

感觉运动系统必须重新校准，以适应正常发生的或病理诱导的感觉输入模式的变化。 对于这一过程的研究，关键问题是确定系统如何评估其感觉输入的变化，并定义产生适应性反应的机制。 这突出了可兴奋细胞的一个普遍问题，即如何随着突触输入的数量或模式的变化适当地缩放或改变其反应。 在许多情况下，突触活动的关键变化通过N-甲基-D-天冬氨酸（NMDA）或代谢型（mGlu）谷氨酸受体传递给神经元。我们建议使用一个简单的系统-电鱼的神经系统，它控制电器官放电（EOD）-来研究感觉流入的改变如何调节运动输出电路的活动，以适应性地改变电路和动物的行为。 感觉流入中的这些改变在CNS中处理，并最终通过NMDA和可能的mGlu受体传递到控制EOD频率的起搏神经元。 这些受体的激活导致这些关键起搏神经元在刺激停止后的放电频率的长期（许多小时）适应性变化。 在这个提议中，我们希望更全面地描述感觉刺激如何引起运动输出的长期变化（EOD频率）;在切片制备中鉴定起搏神经元中NMDA和mGlu受体的激活如何导致其突触后放电率的长期变化;最后，通过在行为受限的动物中阻断这些受体在起搏神经元中的作用来测试它们在控制行为中的作用。

Sensory-motor systems must be recalibrated to adapt to normally-occurring or pathologically-induced changes in the pattern of sensory inputs. For studies of this process, the key questions are pinpointing how the system is appraised of changes in its sensory inputs, and defining the mechanisms by which an adaptive response is generated. This highlights a general problem for excitable cells which is how to scale or vary their responses appropriately with changes in the quantity or pattern of their synaptic inputs. In many cases, critical changes in synaptic activity are communicated to neurons via N-methyl-D- aspartate (NMDA) or metabotropic (mGlu) type glutamate receptors. We propose to use a simple system--the electromotor system of electric fish, which controls the electric organ discharge (EOD)- -to study how alterations in sensory inflow can regulate the activity of motor output circuitry to adaptively change the circuit's and the animal's behavior. These alterations in the sensory inflow are processed in the CNS and ultimately communicated to the pacemaker neurons that control the EOD frequency via NMDA and, possibly, mGlu receptors. Activation of these receptors leads to long-term (many hours) adaptive changes in the firing frequency of these critical pacemaking neurons after the stimulus has ceased. In this proposal we wish to more fully characterize how sensory stimuli induce long-term shifts in motor output (EOD frequency) of behaving animals; identify in a slice preparation how activation of NMDA and mGlu receptors in pacemaking neurons could lead to long-term changes in their postsynaptic firing rates; and, finally, test the role of these receptors in controlling the behavior by blocking them in pacemaking neurons in a restrained behaving animal.