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处，短期可塑性导致突触强度响应于不规则刺激模式（例如这些突触在体内接收的刺激模式）而在宽范围内被调制。突触传递的这种频率依赖性使得能够在突触处进行计算，并且确定在突触前和突触后细胞之间传递的信息的内容。然而，很少有人知道，在兴奋性突触到CA1中间神经元的突触传递的短期可塑性和频率依赖性。像CA1锥体细胞一样，CA1中的中间神经元通过Schaffer侧支轴突接收来自CA3锥体细胞的输入。然而，中间神经元在海马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，因此它们的兴奋性输入的频率依赖性在确定回路中的兴奋和抑制的平衡中将是至关重要的。抑制和兴奋之间的平衡对海马体至关重要，海马体是一个非常容易患癫痫的大脑区域。本提案中的实验使用电生理学来比较短期可塑性和兴奋性突触到CA1中间神经元与锥体细胞的突触传递的频率依赖性，使用传统的刺激范例和基于动作电位计时的体内记录的时间复杂的刺激模式。这些实验将提供有关突触后靶细胞在确定突触前特性中的作用的信息，以及突触传递的频率依赖性如何与神经编码相关。

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.