Three-dimensional Localization of Neurons in Cortical 1 Tetrode Recordings 2 3 4

17 18 Abbreviated Title: 3D neuron localization from tetrode recordings 19 20 for the scanning electron-microscopy; and Drs Partha Mitra and Alexander 40 Polyakov for stimulating early discussions and introducing the use of Femlab. Abstract 43 44 The recording radius and spatial selectivity of an extracellular probe is important 45 for interpreting neurophysiological recordings, but is rarely measured. Moreover, an 46 analysis of the recording biophysics of multisite probes (e.g., tetrodes) can provide for 47 source characterization and localization of spiking single units, but this capability has 48 remained largely unexploited. Here we address both issues quantitatively. 49 Advancing a tetrode (≈40-µm contact separation, tetrahedral geometry) in 5-to-50 10-µm steps, we repeatedly recorded extracellular action potentials (EAP's) of single 51 neurons in visual cortex. Using measured spatial variation of EAP's, the tetrodes' 52 measured geometry, and a volume conductor model of the cortical tissue, we solved the 53 inverse problem of estimating the location and the size of the equivalent dipole model of 54 the spike generator associated with each neuron. 55 Half of the 61 visual neurons were localized within a radius of ≈100 µm, and 95% 56 within ≈130 µm around the tetrode tip (i.e., a large fraction was much further than 57 previously thought). Because of the combined angular sensitivity of the tetrode's leads, 58 location uncertainty was less than half the cell's distance. 59 We quantified the spatial dependence of the probability of cell isolation; the 60 isolated fraction; and the dependence of the recording radius on probe size and equivalent 61 dipole size. We also reconstructed the spatial configuration of sets of simultaneously 62 recorded neurons to demonstrate the potential use of 3D dipole localization for functional 63 anatomy. 64 Finally, we have found that the dipole moment vector, surprisingly, tended to 65 point towards the probe, leading to the interpretation that the equivalent dipole represents 66 a " local lobe " of the dendritic arbor. 67 68 69 3D neuron localization from tetrode recordings Mechler et al. (2011)