We find that through volume conduction, the LFP typically spreads well beyond this microdomain extent, and indeed is observable Ibrutinib ic50 many millimeters distant to the active neuronal tissue in which it is generated. It is worth noting that the conclusion the LFP in general spreads only over a ∼250 μm domain is fundamentally inconsistent

with the evidence indicating that stimulus-evoked and event-related potentials recorded on the scalp in humans reflect a summation of LFP generated in the brain (Luck, 2005, Mitzdorf, 1985, Nunez et al., 1991, Nunez and Srinivasan, 2006 and Schroeder et al., 1991). We have discussed a number of ways in which LFP recordings can be managed to improve their spatial resolution and the precision of their physiological interpretation. We conclude that both physiological factors (e.g., strength, spatial extent and symmetry of activation in the neuronal substrate), and technical factors (e.g., electrode reference site) are critical to understanding the source and sampling area of an LFP, and that any general model of the LFP must account for these factors. All procedures were approved by the IACUC of Trametinib mouse the Nathan Kline Institute. Recordings were made in six awake macaques. Binaural auditory stimuli of tones and BBN were delivered through directional free field speakers. Linear array multielectrodes,

having 23 electrical contacts with either 100 or 200 μm intercontact below spacing were used. Electrodes were advanced downward from the surface of brain with steps of 2 or 4 mm for arrays of 100 or 200 μm spacing, respectively, until they reached the auditory cortex. At each step, responses to 50∼100 repetitions of BBN were recorded. Reference electrodes were positioned above dura. See Supplemental Experimental Procedures for more details. LFP and MUA signals were averaged across trials. CSD was calculated from LFPs by numerical differentiations to approximate the second order spatial derivative of the LFP. One channel at the depth of layer 4 was selected for further analyses. Mean amplitudes were estimated during

a postonset response period (10 ms) during which MUA increased and CSD and LFP signals deflected downward, and baseline amplitudes (−30∼−5 ms from the stimulus onset) were subtracted before derivation of tuning curves. The best frequencies (BFMUA, BFCSD, and BFLFP) and the tuning bandwidths (BWMUA, BWCSD, and BWLFP) were estimated from tuning curves. To quantify tuning curves across recording sites, curves were normalized by their peaks, and were further shifted on the frequency axis to align the BFMUA to zero. The amplitudes of LFP responses to BBN were measured at 24 ms postonset of sound and baseline subtracted at each recording depth. For each penetration site, the distribution of amplitudes was normalized to the mean of absolute amplitudes across depths.