Frequency Dependence of Excitatory Synaptic Transmission

描述(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广泛的范围内被调节，以响应不规则的刺激模式，例如这些突触在体内接收。突触传递的这种频率依赖性使突触的计算成为可能，并决定了突触前和突触后细胞之间传递的信息的内容。然而，对兴奋性突触向CA1中间神经元传递突触的短期可塑性和频率依赖性知之甚少。与CA1锥体细胞类似，CA1内的中间神经元通过Schaffer侧支轴突接受CA3锥体细胞的输入。然而，中间神经元在海马环路中的作用却截然不同。由于这些细胞为CA1锥体细胞提供关键的前馈抑制，它们兴奋输入的频率依赖性将在决定回路中兴奋和抑制的平衡中起关键作用。抑制和兴奋之间的平衡对海马体至关重要，海马体是大脑中极易患癫痫的区域。该方案中的实验使用电生理学来比较兴奋性突触对CA1中间神经元和锥体细胞的突触传递的短期可塑性和频率依赖性，使用传统的刺激范式和基于活体动作电位计时记录的时间复杂刺激模式。这些实验将提供有关突触后目标细胞在决定突触前属性中的作用，以及突触传递的频率依赖如何与神经编码有关的信息。

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.