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Research ArticleResearch Article: Methods/New Tools, Novel Tools and Methods

Synchronous Measurements of Extracellular Action Potentials and Neurochemical Activity with Carbon Fiber Electrodes in Nonhuman Primates

Usamma Amjad, Jiwon Choi, Daniel J. Gibson, Raymond Murray, Ann M. Graybiel and Helen N. Schwerdt
eNeuro 25 June 2024, 11 (7) ENEURO.0001-24.2024; https://doi.org/10.1523/ENEURO.0001-24.2024
Usamma Amjad
1Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15213
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Jiwon Choi
1Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15213
2Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, Maryland 20815
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Daniel J. Gibson
3Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
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Raymond Murray
1Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15213
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Ann M. Graybiel
3Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
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Helen N. Schwerdt
1Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15213
2Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, Maryland 20815
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  • Figure 1.
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    Figure 1.

    A, ECP recording setup for synchronous recording of dopamine and neuronal action potentials as recorded from separate CF electrodes implanted in the monkey striatum (colored purple and green) and connected to electrochemical (FSCV) and EPhys recording systems, respectively. B, Example recordings from ECP system in a task-performing monkey. FSCV-recorded dopamine signals are plotted as a function of time as displayed on a color plot where current changes (color scale) are clearly observed at the redox potentials for dopamine (∼−0.2 and 0.6 V) and its PCA-extracted dopamine concentration change ([ΔDA]) below it. Task events for the display of the initial central cue (C), peripheral reward-predictive target (T), and reward delivery (RW) are displayed as vertical lines. Below this, the concurrent EPhys recording is shown for a small time window (black dashed rectangle) during the dopamine trace, showing the interfering FSCV scan artifacts. A close-up of the EPhys recording between two scan artifacts (green dashed rectangle) is shown to visualize clear spike action potentials (arrowheads on top right inset). The bottom panel shows the signal after high-pass filtering at 250 Hz using forward-only filters as would be applied for standard spike detection algorithms. This period includes a close-up of the scan artifact demonstrating its triggering of multiple threshold (dashed line)-crossings (circles). Three physiological units are also detected but the first of these is largely distorted by the forward-filtering of the artifact.

  • Figure 2.
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    Figure 2.

    Flow chart of temporal interpolation algorithm used to extract spike activity from ECP recordings. Details may be found in the text.

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    Figure 3.

    Temporal interpolation process applied to an example ECP recording. A, Signals from five electrodes containing FSCV scan artifacts, electrode sites are labeled in the legend (c denotes CN site and p denotes putamen site). B, All these signals are then averaged (step 1 in interpolation algorithm). C, The averaged signal is bandpass filtered (BPF) and a threshold is computed (1.75 × STD) to find the positive-crossings and local peaks for each of these (circles). Only periodic peaks are retained (or added if they did not cross the threshold initially). D, Linear interpolation is performed around each of these identified peaks using a window of −3 to 7 ms for each electrode channel. An example is shown for site c34 in the bottom left plot, as well as a close-up on the bottom right, to visualize recorded unit spike activity.

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    Figure 4.

    A, Validation setup showing three different simulated FSCV artifact types (RC, R, Rail; green trace) added onto EPhys-only recording (black trace; session 65B and site p32). B, Top, Spike waveforms projected onto PC space (top) with colored clusters. Bottom, Average spike waveforms for drawn clusters from the PC space (top). Shading represents ± SD.

  • Figure 5.
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    Figure 5.

    Analysis of task modulated-signaling from concurrent recordings of dopamine and spike activity from three sites in the CN and putamen measured from a single session (session 127). A, Top, FSCV color plot; middle, PCA-computed dopamine concentration change ([ΔDA]); and bottom, concurrent measurements of electrical neural activity high-pass filtered (HPF) to visualize spike action potentials. Two windows (blue rectangles) are magnified to show the individual spike action potential waveforms (right). Task events are labeled following notation in Figure 1. B, Left, Average waveform of unit detected (shading represents ± SD). Right, ISI histogram of the detected unit. C, Top, Trial-by-trial raster plot of spike activity (dot) measured in the CN (c34) as aligned to the peripheral target display event (0 s). Ton represents the average time from the peripheral target display event at which the monkey begins fixation on the peripheral target. Bottom, Average spike rate for large and small reward trial conditions (shading represents ± SE). Large and small reward trials are denoted by red and blue colors, respectively. D, Dopamine concentration changes measured at neighboring sites in the CN (c66) and putamen (p15) as aligned to the same events as C for large and small reward conditions (shading represents ± SE). Color coding is the same as in C.

  • Figure 6.
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    Figure 6.

    Dopamine and spike activity recorded concurrently from a single session show diverse responses to behavioral events related to reward size and spatial target direction. A, Average waveform of a putative MSN (top) and its ISI histogram (bottom) as recorded in the CN (c33). B, Raster plot of spike activity for the unit in A as plotted in Figure 5C, except for left (purple) and right (green) peripheral target conditions, demonstrating higher neural responses to gaze of the right peripheral targets than to left targets. C, Dopamine concentration changes measured at a neighboring site in the CN (c54) displaying oppositive sensitivity to target direction (higher for left than for right target) in comparison with the unit in B (top; color coding is the same as in B), and stronger modulation by reward size (bottom; color coding is the same as in Fig. 5C). Only left target conditions are plotted on the bottom panel as reward sensitivity was not observed in right target conditions. D, Same as A except for another unit (putative TAN) recorded in a separate session (69) and site in the putamen (p23). E, Same as B except for large (red) and small (blue) reward conditions. No distinction is observed in the cell firing for the reward size or target direction. F, Dopamine concentration changes measured at neighboring sites in the CN (c62) and putamen (p13) where stronger modulation by reward size is observed in comparison with the unit response in E. Color coding is the same as in E.

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    Table 1.

    Validation results showing percent recovery of spikes extracted after interpolating simulated artifacts relative to spikes extracted from clean EPhys recording for the different types of artifacts (R, RC, and Rail)

    SessionChannelR recoveryRC recoveryRail recovery
    65Bp2387.1386.3979.55
    p3287.2386.983.51
    109Bp3588.6686.0776.07
    c3491.7884.4881.02
    161bp3685.3585.0677.94

Extended Data

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  • Figure 3-1

    Same as Fig. 3 but demonstrating an example with 60  Hz + harmonics noise and the additional steps to remove these signals. (D) After high pass filtering, the noise was enhanced. (E) Unit spike activity is more clearly discernible after interpolating both 60  Hz harmonics noise and the FSCV artifacts. Download Figure 3-1, TIF file.

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eneuro: 11 (7)
eNeuro
Vol. 11, Issue 7
July 2024
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Synchronous Measurements of Extracellular Action Potentials and Neurochemical Activity with Carbon Fiber Electrodes in Nonhuman Primates
Usamma Amjad, Jiwon Choi, Daniel J. Gibson, Raymond Murray, Ann M. Graybiel, Helen N. Schwerdt
eNeuro 25 June 2024, 11 (7) ENEURO.0001-24.2024; DOI: 10.1523/ENEURO.0001-24.2024

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Synchronous Measurements of Extracellular Action Potentials and Neurochemical Activity with Carbon Fiber Electrodes in Nonhuman Primates
Usamma Amjad, Jiwon Choi, Daniel J. Gibson, Raymond Murray, Ann M. Graybiel, Helen N. Schwerdt
eNeuro 25 June 2024, 11 (7) ENEURO.0001-24.2024; DOI: 10.1523/ENEURO.0001-24.2024
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Keywords

  • dopamine
  • electrophysiology
  • fast-scan cyclic voltammetry
  • multimodal electrochemical and electrical recording
  • neurotransmitters
  • striatum

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