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

描述(申请人提供)：神经元的输入/输出属性是可修改的。表征输入/输出属性的变化对于理解神经活动如何随着网络活动的持续变化而变化是至关重要的。虽然有几个由输入驱动的神经兴奋性变化的例子，但尚不清楚正在进行的突触活动如何调节神经元的输入/输出属性。这项研究的长期目标是表征正在进行的突触输入如何影响前额叶皮质(PFC)V层锥体神经元的整合特性。这项提议的第一个具体目标将进一步检验最初的观察结果，即低突触刺激率会改变PFC第五层锥体神经元的兴奋性。这些实验将确定与观察到的变化有关的电导和神经递质受体。这些实验包括从V层PFC神经元胞体进行全细胞膜片钳记录。第二个具体目标将检验这样一种假设，即这种变化发生在树突中的方式取决于刺激的频率和位置。完成这一目标将使我们深入了解可塑性是短期的还是长期的，以及它是自稳的还是与学习有关的。这些实验将包括全细胞、体细胞和树突的记录。第三个具体目标将测试具有不同膜电导谱系的两类神经元的特性变化的差异：那些投射在皮质内的神经元和那些投射在皮质下的神经元。这一特定目的的压倒一切的假设是，输入/输出特性的变化取决于可被修改的特定膜电导。

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.