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Real-time in vivo optogenetic neuromodulation and multielectrode electrophysiologic recording with NeuroRighter.

Laxpati NG, Mahmoudi B, Gutekunst CA, Newman JP, Zeller-Townson R, Gross RE - Front Neuroeng (2014)

Bottom Line: Optogenetic channels have greatly expanded neuroscience's experimental capabilities, enabling precise genetic targeting and manipulation of neuron subpopulations in awake and behaving animals.To address this, we adapted the open-source NeuroRighter multichannel electrophysiology platform for use in awake and behaving rodents in both open and closed-loop stimulation experiments.We then demonstrate the capabilities and versatility of these adaptations in several open and closed-loop experiments, demonstrate spectrographic methods of analyzing the results, as well as discuss artifacts of stimulation.

View Article: PubMed Central - PubMed

Affiliation: Translational Neuroengineering Group, Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine Atlanta, GA, USA ; Department of Neurosurgery, Emory University School of Medicine Atlanta, GA, USA.

ABSTRACT
Optogenetic channels have greatly expanded neuroscience's experimental capabilities, enabling precise genetic targeting and manipulation of neuron subpopulations in awake and behaving animals. However, many barriers to entry remain for this technology - including low-cost and effective hardware for combined optical stimulation and electrophysiologic recording. To address this, we adapted the open-source NeuroRighter multichannel electrophysiology platform for use in awake and behaving rodents in both open and closed-loop stimulation experiments. Here, we present these cost-effective adaptations, including commercially available LED light sources; custom-made optical ferrules; 3D printed ferrule hardware and software to calibrate and standardize output intensity; and modifications to commercially available electrode arrays enabling stimulation proximally and distally to the recording target. We then demonstrate the capabilities and versatility of these adaptations in several open and closed-loop experiments, demonstrate spectrographic methods of analyzing the results, as well as discuss artifacts of stimulation.

No MeSH data available.


Hippocampal LFP response to alternative, customizable optical stimulation patterns in the MS. (A–C) Jittering the frequency of 50 mW/mm2, 10 ms stimulation pulses ±5 Hz within a normal distribution centered on 23 Hz (A) produced a peristimulus average waveform (B) similar to fixed-frequency simulation (Figure 3), but with temporal variance in the peak response frequency during stimulation (C). This stimulation reduced the power at frequencies <10 Hz. (D–F) Poisson 50 mW/mm2 10 ms pulses generated with a frequency of 23 Hz (D) demonstrated a similar LFP peristimulus average response (E) and a broadband increase in power that did not influence <10 Hz power (F). (G–I) Four 50 mW/mm2, 42 Hz, 10 ms pulses generated at a 7 Hz burst frequency (G) produced a sinusoidal peristimulus waveform (H) similar to constant 42 Hz stimulation (Figure 3). Harmonics of the 7 Hz oscillation widely varied in amplitude (I), likely due to constructive and destructive interference between the 42 and 7 Hz stimulation response signals. (J–L) Continuous sinusoidal oscillation (J) generated a sinusoidal peristimulus average (K), of lower amplitude than pulsed stimulation. Power was concentrated at the stimulus frequency (L), with reduced harmonic power.
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Figure 7: Hippocampal LFP response to alternative, customizable optical stimulation patterns in the MS. (A–C) Jittering the frequency of 50 mW/mm2, 10 ms stimulation pulses ±5 Hz within a normal distribution centered on 23 Hz (A) produced a peristimulus average waveform (B) similar to fixed-frequency simulation (Figure 3), but with temporal variance in the peak response frequency during stimulation (C). This stimulation reduced the power at frequencies <10 Hz. (D–F) Poisson 50 mW/mm2 10 ms pulses generated with a frequency of 23 Hz (D) demonstrated a similar LFP peristimulus average response (E) and a broadband increase in power that did not influence <10 Hz power (F). (G–I) Four 50 mW/mm2, 42 Hz, 10 ms pulses generated at a 7 Hz burst frequency (G) produced a sinusoidal peristimulus waveform (H) similar to constant 42 Hz stimulation (Figure 3). Harmonics of the 7 Hz oscillation widely varied in amplitude (I), likely due to constructive and destructive interference between the 42 and 7 Hz stimulation response signals. (J–L) Continuous sinusoidal oscillation (J) generated a sinusoidal peristimulus average (K), of lower amplitude than pulsed stimulation. Power was concentrated at the stimulus frequency (L), with reduced harmonic power.

Mentions: In Figures 4 and 5, each stimulus pulse occurred at the same frequency during the stimulation epoch, producing a very frequency-specific increase in power in the hippocampal LFP. In the first experiment in alternative stimulation patterns, we introduced a jitter in the interpulse interval based on a random normal distribution of ±5 Hz surrounding the arbitrarily examined stimulus frequency of 23 Hz (Figure 7A). The resulting 50 mW/mm2, 10 ms pulsed stimulus produced similar depolarization/hyperpolarization responses to that of the fixed-frequency pulsed stimulation, as seen in the peristimulus averages generated (Figure 7B), but notable differences were observed spectrographically (Figure 7C). First, the response was more broad and effectively tracked the varying stimulation frequency. This is reflective of the neural networks ability to track the variability introduced into to the stimulation signal. This variability may be more reflective of normal neurologic signals, which rarely have the frequency-specificity of artificial stimulation. Note that a stimulation harmonic is also apparent, with similar variability as seen in the primary response signal. The spectrogram also demonstrates an increase in power across frequencies greater than 25 Hz during the stimulation, and a concomitant reduction in power at frequencies less than 10 Hz.


Real-time in vivo optogenetic neuromodulation and multielectrode electrophysiologic recording with NeuroRighter.

Laxpati NG, Mahmoudi B, Gutekunst CA, Newman JP, Zeller-Townson R, Gross RE - Front Neuroeng (2014)

Hippocampal LFP response to alternative, customizable optical stimulation patterns in the MS. (A–C) Jittering the frequency of 50 mW/mm2, 10 ms stimulation pulses ±5 Hz within a normal distribution centered on 23 Hz (A) produced a peristimulus average waveform (B) similar to fixed-frequency simulation (Figure 3), but with temporal variance in the peak response frequency during stimulation (C). This stimulation reduced the power at frequencies <10 Hz. (D–F) Poisson 50 mW/mm2 10 ms pulses generated with a frequency of 23 Hz (D) demonstrated a similar LFP peristimulus average response (E) and a broadband increase in power that did not influence <10 Hz power (F). (G–I) Four 50 mW/mm2, 42 Hz, 10 ms pulses generated at a 7 Hz burst frequency (G) produced a sinusoidal peristimulus waveform (H) similar to constant 42 Hz stimulation (Figure 3). Harmonics of the 7 Hz oscillation widely varied in amplitude (I), likely due to constructive and destructive interference between the 42 and 7 Hz stimulation response signals. (J–L) Continuous sinusoidal oscillation (J) generated a sinusoidal peristimulus average (K), of lower amplitude than pulsed stimulation. Power was concentrated at the stimulus frequency (L), with reduced harmonic power.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4217045&req=5

Figure 7: Hippocampal LFP response to alternative, customizable optical stimulation patterns in the MS. (A–C) Jittering the frequency of 50 mW/mm2, 10 ms stimulation pulses ±5 Hz within a normal distribution centered on 23 Hz (A) produced a peristimulus average waveform (B) similar to fixed-frequency simulation (Figure 3), but with temporal variance in the peak response frequency during stimulation (C). This stimulation reduced the power at frequencies <10 Hz. (D–F) Poisson 50 mW/mm2 10 ms pulses generated with a frequency of 23 Hz (D) demonstrated a similar LFP peristimulus average response (E) and a broadband increase in power that did not influence <10 Hz power (F). (G–I) Four 50 mW/mm2, 42 Hz, 10 ms pulses generated at a 7 Hz burst frequency (G) produced a sinusoidal peristimulus waveform (H) similar to constant 42 Hz stimulation (Figure 3). Harmonics of the 7 Hz oscillation widely varied in amplitude (I), likely due to constructive and destructive interference between the 42 and 7 Hz stimulation response signals. (J–L) Continuous sinusoidal oscillation (J) generated a sinusoidal peristimulus average (K), of lower amplitude than pulsed stimulation. Power was concentrated at the stimulus frequency (L), with reduced harmonic power.
Mentions: In Figures 4 and 5, each stimulus pulse occurred at the same frequency during the stimulation epoch, producing a very frequency-specific increase in power in the hippocampal LFP. In the first experiment in alternative stimulation patterns, we introduced a jitter in the interpulse interval based on a random normal distribution of ±5 Hz surrounding the arbitrarily examined stimulus frequency of 23 Hz (Figure 7A). The resulting 50 mW/mm2, 10 ms pulsed stimulus produced similar depolarization/hyperpolarization responses to that of the fixed-frequency pulsed stimulation, as seen in the peristimulus averages generated (Figure 7B), but notable differences were observed spectrographically (Figure 7C). First, the response was more broad and effectively tracked the varying stimulation frequency. This is reflective of the neural networks ability to track the variability introduced into to the stimulation signal. This variability may be more reflective of normal neurologic signals, which rarely have the frequency-specificity of artificial stimulation. Note that a stimulation harmonic is also apparent, with similar variability as seen in the primary response signal. The spectrogram also demonstrates an increase in power across frequencies greater than 25 Hz during the stimulation, and a concomitant reduction in power at frequencies less than 10 Hz.

Bottom Line: Optogenetic channels have greatly expanded neuroscience's experimental capabilities, enabling precise genetic targeting and manipulation of neuron subpopulations in awake and behaving animals.To address this, we adapted the open-source NeuroRighter multichannel electrophysiology platform for use in awake and behaving rodents in both open and closed-loop stimulation experiments.We then demonstrate the capabilities and versatility of these adaptations in several open and closed-loop experiments, demonstrate spectrographic methods of analyzing the results, as well as discuss artifacts of stimulation.

View Article: PubMed Central - PubMed

Affiliation: Translational Neuroengineering Group, Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine Atlanta, GA, USA ; Department of Neurosurgery, Emory University School of Medicine Atlanta, GA, USA.

ABSTRACT
Optogenetic channels have greatly expanded neuroscience's experimental capabilities, enabling precise genetic targeting and manipulation of neuron subpopulations in awake and behaving animals. However, many barriers to entry remain for this technology - including low-cost and effective hardware for combined optical stimulation and electrophysiologic recording. To address this, we adapted the open-source NeuroRighter multichannel electrophysiology platform for use in awake and behaving rodents in both open and closed-loop stimulation experiments. Here, we present these cost-effective adaptations, including commercially available LED light sources; custom-made optical ferrules; 3D printed ferrule hardware and software to calibrate and standardize output intensity; and modifications to commercially available electrode arrays enabling stimulation proximally and distally to the recording target. We then demonstrate the capabilities and versatility of these adaptations in several open and closed-loop experiments, demonstrate spectrographic methods of analyzing the results, as well as discuss artifacts of stimulation.

No MeSH data available.