Biophysics of Extracellular Action Potentials

The goal of this thesis is to analyze the generation of single unit extracellular action potentials (EAPs), and to explore pertinent issues in the interpretation of EAP recordings. I use the line source approximation to model the EAP produced by individual neurons. I compare simultaneous intracellular and extracellular recordings of CA1 pyramidal neurons in vivo with simulations using the same cells’ reconstructions. The model accurately reproduces both the waveform and the amplitude of the EAPs. The composition of ionic currents is reflected in the features of each cell’s EAP, while dendritic morphology has little impact. I compared constraining a compartmental model to fit the EAP with matching the intracellular action potential (IAP). I find that the IAP method underconstrains the parameters. The distinguishing characteristics of the EAP constrain the parameters and are fairly invariant to electrode position and cellular morphology. I conclude that matching EAP recordings are an excellent means of constraining compartmental models. I recorded spikes from cat primary visual cortex (V1) and recreated them in the model. I calculated the distance at which an electrode could record the EAPs given the prevalent background noise. My analysis suggests that in the superficial cortical layers 50%–80% of the neurons were active, while in deeper layers only 10%–20% were active. I analyzed the bias towards recording the large neurons in the deep layers. If the detection and clustering algorithm is sensitive enough to include low-amplitude spikes then bias is moderate. If only high amplitude units (> 200 μV) are picked up, then recording will be significantly biased towards the deep layers. The majority of spikes in cortex had a negative peak with a mean of -0.11 mV, but a minority of units (<10%) had a large positive peak of up to 1.5 mV. Simulations demonstrate that a pyramidal neuron may generate a negative spike with amplitude greater than 1 mV, but a positive spike of at most 0.5 mV. I conclude that high-amplitude positive spikes cannot result from a single neuron EAP. I suggest that they may result from synchronized action potentials in groups of L5 pyramidal neurons.