Frequency Dependence of Excitatory Synaptic Transmission

描述（由申请人提供）：在CA1锥体细胞上的兴奋性突触，短期可塑性导致突触强度在大范围内被调节，以响应这些突触在体内接受的不规则刺激模式。突触传递的这种频率依赖性使突触能够进行计算，并决定突触前和突触后细胞之间传递的信息的内容。然而，关于兴奋性突触到CA1中间神经元的突触传递的短期可塑性和频率依赖性知之甚少。与CA1锥体细胞一样，CA1的中间神经元通过Schaffer侧轴突接受来自CA3锥体细胞的输入。然而，中间神经元在海马体回路中的作用是完全不同的。由于这些细胞对CA1锥体细胞提供关键的前馈抑制，它们的兴奋性输入的频率依赖性将是决定电路中兴奋和抑制平衡的关键。抑制和兴奋之间的平衡对海马体至关重要，海马体是大脑中易患癫痫的区域。本实验采用电生理学方法，利用传统刺激模式和基于体内动作电位计时记录的时间复杂刺激模式，比较CA1中间神经元和锥体细胞在兴奋性突触上突触传递的短期可塑性和频率依赖性。这些实验将提供突触后靶细胞在决定突触前特性中的作用，以及突触传递的频率依赖性如何与神经编码相关的信息。

DESCRIPTION (provided by applicant): At excitatory synapses onto CA1 pyramidal cells, short-term plasticity causes synaptic strength to be modulated over a wide range in response to irregular stimulus patterns such as these synapses receive in vivo. This frequency-dependence of synaptic transmission enables computation at synapses, and determines the content of information transmitted between the pre- and post-synaptic cells. Very little is known, however, about short-term plasticity and frequency-dependence of synaptic transmission at excitatory synapses onto CA1 interneurons. Like CA1 pyramidal cells, interneurons in CA1 receive inputs from CA3 pyramidal cells via Schaffer collateral axons. However, the role of interneurons in the hippocampal circuit is quite different. Since these cells provide critical feed forward inhibition to the CA1 pyramidal cells, the frequency-dependence of their excitatory inputs will be crucial in determining the balance of excitation and inhibition in the circuit. The balance between inhibition and excitation is critical to the hippocampus, a brain region that is highly susceptible to epilepsy. Experiments in this proposal use electrophysiology to compare short-term plasticity and the frequency dependence of synaptic transmission at excitatory synapses onto CA1 interneurons vs. pyramidal cells, using traditional stimulus paradigms and temporally complex stimulus patterns based on in vivo recordings of action potential timing. These experiments will provide information about the role of the postsynaptic target cell in determining presynaptic properties, and how the frequency dependence of synaptic transmission is related to neural coding.