Biology of electrophysiology

In this chapter we will go over the biology related to electrophysiology. Some of the biology is covered in other neuroscience textbooks so in this book we will focus on the measures we can from slice electrophysiology and what they mean. This section is designed for people who will do electrophysiology and those who don’t but want to understand why electrophysiologist capture the data that they do.

Core assumptions¶

Isopotential¶

One of the core assumptions of many patch-clamp electrophysiology experiments make is that of isopotentiality. We essentially assume the cell is a perfect sphere and the environment (membrane voltage, current, etc) is the same everywhere in that sphere. This is absolutely not true. However, assuming a cell is isopential gets us pretty far into understanding how neurons work for things like excitability and membrane resistance. But, it can fail in some specific examples. When we do whole cell experiments to test HCN currents we assume the channels are primarily located in the cell body. Many cells express HCN channels but not all cells express it in the same region of the cell and we have a harder time detecting HCN currents if the channels are in the dendrites or axon. We often assume that any voltage we clamp the cell body at is the voltage the dendrites will be at. This is called space-clamp. In reality we have a limited ability to clamp the entire cell, including dendritic arbor, at a specific voltage. This can impact how well we can measure synaptic events and dendrites can also change spiking behavior.

Cell body-centric experiments¶

Many patch-clamp electrophysiology utilize the cell body as a point of reference. We inject current into the cell body to generate action potentials. We recorded PSCs from the cell body. Action potentials in the cell body are the end result of the summation of dendritic currents not somatically generated currents. Action potentials in the cell body can be influenced by dendritic properites such as in neo-cortical pyramidal cells. While we record PSCs in the soma, there are likely many synapses that don’t influence soma membrane voltage but instead influence other synaptic currents on the dendritic arbor. We only record a subset of all PSCs in a cell which could biase our experiments.

Outro¶

None of these assumptions mean we should not do the experiments that we do or throw out the data we have. We just need to be aware of the limitations that patch-clamp electrophysiology has so we can make better inferences from that data. The better we understand the biology and limitations of our techniques the better we can make causal inferences from our data.