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至关重要。虽然有几个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/输出特性。本研究的长期目标是研究突触输入对前额叶皮层第五层锥体神经元整合特性的影响。本提案的第一个具体目标将进一步测试最初的观察，即低速率的突触刺激产生的变化，在第五层的PFC锥体神经元的兴奋性。这些实验将确定电导和神经递质受体参与所观察到的变化。这些实验涉及全细胞膜片钳记录从索马的第V层PFC神经元。第二个具体的目标将测试假设的变化发生在树突的方式，取决于频率和刺激的网站。这个目标的完成将提供洞察力的可塑性是短期或长期的，它是稳态或pueretics参与学习。这些实验将涉及全细胞体细胞和树突记录。第三个具体目标是测试两类具有不同膜电导的神经元特性变化的差异：在皮层内投射的神经元和在皮层下投射的神经元。这一特定目标的首要假设是，输入/输出特性的变化取决于可用于修改的特定膜电导。

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.