Can One Concurrently Record Electrical Spikes from Every Neuron in a Mammalian Brain?

Abstract

The classic approach to measure the spiking response of neurons involves the use of metal electrodes to record extracellular potentials. Starting over 60 years ago with a single recording site, this technology now extends to ever larger numbers and densities of sites. We argue, based on the mechanical and electrical properties of existing materials, estimates of signal-to-noise ratios, assumptions regarding extracellular space in the brain, and estimates of heat generation by the electronic interface, that it should be possible to fabricate rigid electrodes to concurrently record from essentially every neuron in the cortical mantle. This will involve fabrication with existing yet nontraditional materials and procedures. We further emphasize the need to advance materials for improved flexible electrodes as an essential advance to record from neurons in brainstem and spinal cord in moving animals.

Keywords: action potentials; connectomics; cortex; electrodes; multisite recording; neurocomputation.

Figure 1.. Schematic of the proposed stiff electrode.

(a) The proposed triangular grid of electrodes spaced on top of primary vibrissa sensory cortex. Image from Knutsen et al. (2016). (b) The electrode is constructed of a diamond shaft that is covered with five layers. First is the leads and the mineral insulation between leads, second is mineral insulation, third is a conduction shield, fourth is a second is mineral insulation, and fifth is the electrode pads. Each pad is connected to one lead via a thru-hole interconnects that pierce the shield. Illustration is not to scale. (c) The multi-electrode shaft with an expanded view of the face to show the arrangement of pads.

Figure 2.. A state-of-the-art rigid probe.

(a) Photograph of the distal 68 sites of the 960 sites on a shank of a Neuropixels probe. The shank is 10 mm long, 70 µm wide, and 24 µm thick, with 12 µm by 12 µm TiN recording sites pitched at 2 per 20 µm of shank length. (b) Two example recordings from Neuropixels probe pads. The probe was chronically implanted in rat prefrontal cortex one day prior to data acquisition. Blue traces and green traces are 30 raw traces in the vicinity of a spike near the top (green) and bottom (blue) of the probe; black lines are average of those traces. Adapted from Jun et al. (2017).

Figure 3.. A state-of-the-art flexible probe.

(a) The electrode is constructed of gold pads and epoxy insulators. A diamond shank provides temporary rigidity for insertion. (b) A flexible multi-channel neural probe fabricated by electron beam lithography, with a shank width of 8 µm, thickness of 0.8 µm, and electrode pad size of 5 µm by 15 µm. (c) Representative electrical traces from the probe in panel b. (d) Three dimensional reconstruction of vasculature by in vivo two-photon microscopy (Kleinfeld et al., 1998) around a probe (red). Data obtained two months after implantation and shown as a maximum projection 100Ð320µm below the pia. Adapted from Wei et al. (2018).