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, 4 (4), 041502

Utah Optrode Array Customization Using Stereotactic Brain Atlases and 3-D CAD Modeling for Optogenetic Neocortical Interrogation in Small Rodents and Nonhuman Primates

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Utah Optrode Array Customization Using Stereotactic Brain Atlases and 3-D CAD Modeling for Optogenetic Neocortical Interrogation in Small Rodents and Nonhuman Primates

Ronald W Boutte et al. Neurophotonics.

Abstract

As the optogenetic field expands, the need for precise targeting of neocortical circuits only grows more crucial. This work demonstrates a technique for using Solidworks® computer-aided design (CAD) and readily available stereotactic brain atlases to create a three-dimensional (3-D) model of the dorsal region of area visual cortex 4 (V4D) of the macaque monkey (Macaca fascicularis) visual cortex. The 3-D CAD model of the brain was used to customize an [Formula: see text] Utah optrode array (UOA) after it was determined that a high-density ([Formula: see text]) UOA caused extensive damage to marmoset (Callithrix jacchus) primary visual cortex as assessed by electrophysiological recording of spiking activity through a 1.5-mm-diameter through glass via. The [Formula: see text] UOA was customized for optrode length ([Formula: see text]), optrode width ([Formula: see text]), optrode pitch ([Formula: see text]), backplane thickness ([Formula: see text]), and overall form factor ([Formula: see text]). Two [Formula: see text] UOAs were inserted into layer VI of macaque V4D cortices with minimal damage as assessed in fixed tissue cytochrome oxidase staining in nonrecoverable surgeries. Additionally, two [Formula: see text] arrays were implanted in mice (Mus musculus) motor cortices, providing early evidence for long-term tolerability (over 6 months), and for the ability to integrate the UOA with a Holobundle light delivery system toward patterned optogenetic stimulation of cortical networks.

Keywords: 3-D CAD model; computer–brain interface; macaque monkey; neocortical stimulation; optical interrogation; optogenetics.

Figures

Fig. 1
Fig. 1
Stereotactic method for customizing UOAs. (a) 3-D CAD brain modeling of macaque V4D using Calabrese atlas plates with highlighted Paxinos regions. A 10-mm section of V4D is selected for 3-D CAD modeling, and the section’s 23 atlas plates have been spaced at 450  μm simulating their location within the macaque brain. (b) Two 3-D CAD models of the UOA shown virtually implanted in V4D (13×13 array with TGV and a smaller 8×6); both devices are shown implanted into the 3-D CAD brain model. (c) A completed soda-lime glass 8×6 UOA, and (d) histological results showing successful macaque V4D implantation.
Fig. 2
Fig. 2
(a) A 13×13 Solidworks® 3-D model of the high-density UOA with a Ø1.5-mm TGV. (b) High density array shown just prior to insertion resting on a marmoset’s primary visual cortex after craniotomy and durotomy have been performed. (c) Postfixation tissue damage assessment shows the array caused vascular damage as well as damage from the trauma of insertion, where high amounts of tissue have been compressed between the array’s optrodes. Histological assessment of tissue damage was not performed due to the level of tissue damage seen following device explantation. The white arrows mark the insertion location of a single 150-μm electrode which was successful in recording neural spiking during postinsertion optrode illumination. Active neural action potentials indicated the neural tissue close to the optrodes around the TGV were still firing.
Fig. 3
Fig. 3
(a) A portion of the Calabrese atlas plates as captured from the Scalable Brain Atlas viewer showing the Paxinos region V4D in Solidworks® with each of the Paxnos regions outlined with a B-spline. (a) Conceptualized Solidworks® 3-D model with lofts between the Paxinos regions of each plate of V4D shown between the starting and ending plates. (c) Sagittal view of the 3-D model of V4D with insertion marks where the 8×6 array has been virtually inserted. The white arrows mark the centroid of interest for illumination of layer IV.
Fig. 4
Fig. 4
(Top left) Design parameters for both 13×13 and the 8×6 arrays set to the same scale. (Top right) Side-by-side comparison of the 13×13 high density array and the much smaller 8×6 UOA. Key differences are wider optrode spacing and the removal of all sharp edges that may contact neural tissue on the UOA. Note: (Bottom left) Volumetric representation of neural tissue surrounding optrodes. Each optrode compresses the tissue into the space between optrodes as they penetrate: (a) the 1.50  mm×0.250  mm×0.250  mm optrode has a tissue volume to optrode volume of 2.581, (b) the 0.500  mm×0.250  mm×0.250  mm optrode has a tissue volume to optrode volume of 2.921, and (c) the 0.500  mm×Ø0.075  mm optrode has a tissue volume to optrode volume of 40.11. (Bottom right) Paxinos region V4D with laminae conceptualized showing array tips at the boundary of layers III and IV.
Fig. 5
Fig. 5
(a) A customized 8×6 UOA to specifically target layer IV of Paxinos macaque area V4D. The UOA is fabricated out of soda-lime microscope slides using maskless wafer-level microfabrication processes. (b) Postperfusion histochemical staining with cytochrome oxidase of sagittal sections of area V4D showed the array was successfully inserted into V4D and reached the boundary between layers III and IV, which would allow for illumination of layer IV during optogenetic studies. The same device was successfully used for holographic projection into motor cortex of the common mouse.
Fig. 6
Fig. 6
(a) View of the cortical connector from below after alignment, projecting a pattern of seven lit fibers. (b) The cortical connector with the UOA implanted in a mouse.

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