Ih-Dependent Regulation of Intrinsic Excitability in CA1 Pyramidal Neurons

6. 项目总结

6. Project Summary This proposal is designed to investigate the relationship between the hyperpolarization-activated cation current (I{h}) and intrinsic excitability (IE) of CA1 pyramidal neurons. Previous work demonstrated enhanced or reduced IE following the induction of long-term depression (LTD) and long-term potentiation (LTP), respectively, and several physiological studies have implicated I{h} as the most likely mediator of IE plasticity (Fan et al., 2005; Brager and Johnston, 2007; Narayanan and Johnston, 2007). However, all evidence describing the plasticity of I{h}mediated IE comes from indirect measurements of I{h} using the whole cell current-clamp method. The mechanism underlying this phenomenon therefore remains unclear, and represents a substantial gap in our understanding of the regulation of IE in these neurons. This proposal investigates the biophysical mechanism of IE plasticity directly, using voltage-clamp methods capable of determining the biophysical properties of single h-channels (the ion channels responsible for I{h}) as the primary tool. Specifically, the reduction in IE following LTP and the increase in IE following LTD will be investigated. This work will represent a substantial contribution to our understanding of IE homeostasis in CA1 pyramidal neurons.