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, 15 (4), 046032

Wireless Opto-Electro Neural Interface for Experiments With Small Freely Behaving Animals

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Wireless Opto-Electro Neural Interface for Experiments With Small Freely Behaving Animals

Yaoyao Jia et al. J Neural Eng.

Abstract

Objective: We have developed a wireless opto-electro interface (WOENI) device, which combines electrocorticogram (ECoG) recording and optical stimulation for bi-directional neuromodulation on small, freely behaving animals, such as rodents.

Approach: The device is comprised of two components, a detachable headstage and an implantable polyimide-based substrate. The headstage establishes a bluetooth low energy (BLE) bi-directional data communication with an external custom-designed USB dongle for receiving user commands and optogenetic stimulation patterns, and sending digitalized ECoG data.

Main results: The functionality and stability of the device were evaluated in vivo on freely behaving rats. When the animal received optical stimulation on the primary visual cortex (V1) and visual stimulation via eyes, spontaneous changes in ECoG signals were recorded from both left and right V1 during four consecutive experiments with 7 d intervals over a time span of 21 d following device implantation. Immunostained tissue analyses showed results consistent with ECoG analyses, validating the efficacy of optical stimulation to upregulate the activity of cortical neurons expressing ChR2.

Significance: The proposed WOENI device is potentially a versatile tool in the studies that involve long-term optogenetic neuromodulation.

Figures

Figure 1
Figure 1
(a) A simplified conceptual representation of the WOENI system for optical stimulation and ECoG recording on small freely behaving rats. (b) A 3D view of the WOENI device prototype, including a detachable headstage and a polyimide-based substrate integrating four addressable µLEDs and two epidural recording microelectrodes.
Figure 2
Figure 2
(a) A simplified block diagram of the key building blocks involved in the headstage. Schematic diagram of a single channel of the optical stimulation (b) and the AFE (c).
Figure 3
Figure 3
Simplified control flowchart of the MCU firmware.
Figure 4
Figure 4
The fabrication procedure of the polyimide-based substrate.
Figure 5
Figure 5
(a) Anatomical location of the polyimide-based substrate on rat brain. (b) WOENI device with four optical stimulation and two ECoG recording channels. In vivo experimental setup for (c) optical stimulation on V1 and (d) visual stimulation.
Figure 6
Figure 6
(a) Theoretical estimate and measured current through one of the µLEDs used in the WOENI device as a function of the digital potentiometer input. (b) Light intensity of the µLED vs. current. (c) Two-channel AFE frequency response. (d) Input-referred voltage noise spectral density of 2-ch AFEs. (e) Changes in the gold microelectrode impedance magnitude and phase vs. frequency.
Figure 7
Figure 7
c-Fos expression in the left and right V1 of (a) rat #1 and (b) the non-transfected rat with optical stimulation on the left V1.
Figure 8
Figure 8
Examples of 2 s long ECoG data recorded from the left and right V1 of (a) rat #2, (b) rat #3, and (c) the non-transfected rat, with V1 optical stimulation flags on the stimulated side. RMS values of the ECoG recorded from Ch1-left and Ch2-right in each experiment performed on (d) rat #2, (e) rat #3, and (f) the non-transfected rat, indicating the optically stimulated V1. Evoked-to-spontaneous (E/S) ECoG RMS ratios of the experiments performed on (g) rat #2 and (h) rat #3, and (i) the non-transfected rat.
Figure 9
Figure 9
Time-frequency maps of the averaged and normalized PSD from two ECoG channels of (a) rat #2, (b) rat #3, and (c) the non-transfected rat, within 1~200 Hz frequency range and 1 s time window, with stimulation markers. The dashed line indicates the 1~40 Hz frequency band, where most of the ECoG power has been concentrated.
Figure 10
Figure 10
(a) Averaged time-varying ECoG power for Ch1-left and Ch2-right channels of (a) rat #2, (b) rat #3, and (c) the nontransfected rat, within 1~40 Hz band and 1s time window, with stimulation markers.
Figure 11
Figure 11
Instantaneous phase of the ECoG from Ch1-left and Ch2-right channels of (a) rat #2, (b) rat #3, and (c) non-transfected rat, within 1~40 Hz band and 1s time window, with stimulation markers. The dashed line indicates the phase locking period.
Figure 12
Figure 12
Time-varying ECoG power from Ch1-left and Ch2-right channels in a single trial at visual angles of (a) VA = 0°, (b) VA = 180°, (c) VA = −90°, and (d) VA = 90°, within 1~40 Hz band and 10 s time window, with stimulation markers.
Figure 13
Figure 13
Comparing ECoG power in each trial in experiments 1~4, marked based on VA (orientation) and trial number (radius). Grey: low ECoG power in both channels, Orange: high ECoG power in both channels. Blue: higher ECoG power in Ch1-left. Green: higher ECoG power in Ch2-right.

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