Synaptic-Driven Changes in Intrinsic Excitability of Layer V Pyramidal Neurons

描述（由申请人提供）：神经元的输入/输出属性是可修改的。描述输入/输出属性的变化对于理解神经活动如何响应网络活动的持续变化是必要的。虽然神经兴奋性的输入驱动变化有几个例子，但尚不清楚正在进行的突触活动如何调节神经元的输入/输出特性。本研究的长期目标是描述持续的突触输入如何影响前额叶皮层（PFC） V层锥体神经元的整合特性。本研究的第一个具体目标是进一步验证最初的观察结果，即低频率的突触刺激会使pfc第V层锥体神经元的兴奋性发生变化。这些实验将确定所观察到的变化中涉及的电导和神经递质受体。这些实验使用全细胞膜片钳记录V层PFC神经元的体细胞。第二个具体目标将检验树突发生变化的方式取决于刺激的频率和位置的假设。这一目标的完成将有助于深入了解可塑性是短期的还是长期的，以及它是自我平衡的还是被认为参与学习的。这些实验将包括全细胞体细胞和树突记录。第三个具体目标将测试两类具有不同膜传导谱的神经元的特性变化的差异：那些在皮层内投射的神经元和那些在皮层下投射的神经元。这一特定目标的最重要假设是，输入/输出特性的变化取决于可修改的特定膜电导。

DESCRIPTION (provided by applicant): The input/output properties of a neuron are modifiable. Characterizing changes in input/output properties is imperative to understanding how neural activity changes in response to ongoing changes in network activity. While there are several examples of input-driven changes in neural excitability, it is not known how ongoing synaptic activity modulates the input/output properties of a neuron. The long-term goal of the proposed research is characterize how ongoing synaptic input affects the integrative properties of layer V pyramidal neurons in prefrontal cortex (PFC). The first specific aim of this proposal will further test the initial observation that low rates of synaptic stimulation produce changes in the excitability of pyramidal neurons in layer V of PFC. These experiments will identify the conductances and neurotransmitter receptors involved in the observed changes. These experiments involve whole-cell patch clamp recordings from the soma of layer V PFC neurons. The second specific aim will test the hypothesis that the changes occur in the dendrites in a manner that depends on the frequency and site of stimulation. Completion of this aim will provide insight into whether the plasticity is short-term or long-term and whether it is homeostatic or putatively involved in learning. These experiments will involve both whole-cell somatic and dendritic recordings. The third specific aim will test for differences in changes in the properties of two classes of neurons with different repertoires of membrane conductances: those that project within the cortex and those that project subcortically. The overriding hypothesis of this specific aim is that changes in input/output properties depend on the specific membrane conductances available to be modified.