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官输入的变化，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，即如何根据突触输入的数量或模式的变化适当地调整或改变它们的反应。在许多情况下，突触活动的关键变化是通过n -甲基- d -天冬氨酸（NMDA）或代谢（mGlu）型谷氨酸受体传递给神经元的。我们建议使用一个简单的系统——电鱼的电机系统，它控制电器官放电（EOD）——来研究感觉流入的改变如何调节电机输出电路的活动，从而自适应地改变电路和动物的行为。这些感觉流入的改变在中枢神经系统中被处理，并最终通过NMDA和mGlu受体传递给控制EOD频率的起搏器神经元。在刺激停止后，这些受体的激活导致这些关键起搏神经元放电频率的长期（许多小时）适应性变化。在这个提议中，我们希望更充分地描述感觉刺激如何诱导行为动物的运动输出（EOD频率）的长期变化；在切片制备中确定起搏神经元中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，测试这些受体在控制行为中的作用，方法是在行为受限的动物体内阻断它们的起搏神经元。

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.