Medial orbitofrontal inactivation does not affect economic choice
- NIDA Intramural Research Program, United States
- University of Maryland School of Medicine, United States
- The Johns Hopkins University, United States
Figures
Figure 1
Inactivation of medial OFC on Economic Choice Behavior in Rats during the Cue Period.
(A) Illustrative example of a single trial on the choice task. White noise cues the availability to initiate a trial by nosepoking within a central port. Images representing the current offer emerge on both screens after a 1s hold. Rats must then continue to hold for 1s, while visualizing the offers, before the white noise is turned off indicating that the animal can then touch one of the screens in order to make a choice. The shapes of the two displayed symbols signify the goods being offered (i.e. vertical bars and crescents), whereas the number of segmentations of the symbols indicate the number of pellets available for each good. For each session, rats experience one pair of the 10 possible pairs of learned associations. (B) Design for the inactivation experiment. (C) Histological verification of viral expression (middle) and fiber placement (left) for each of the rats at ~4.7 mm anterior of bregma. Example of NpHR3.0-eYFP expression (green) and DAPI (blue) (right).
Figure 2 with 1 supplement
Effects of Optogenetic Inhibition of Medial OFC on Economic Choice.
(A) Typical examples of observed behavior on the choice task during sessions with inactivation of medial OFC using halorhodopsin (patent fiber, right panel) or during control sessions (blocked fiber, left panel). The trials were equally split with the laser either on (yellow) or off (grey). (B) Average behavior of all sessions on the choice task for blocked (n = 50, left) and patent fibers (n = 50, right) and for laser-on (yellow curves) and laser-off (grey curves) trials. To show the mean behavior for all sessions, the chosen offers from each session were first realigned to the IP of that session before being averaged. Note that the two curves, laser-on and laser-off, are overlapping one another in most panels. The dark grey dotted line shows the average behavior expected if all sessions shifted to an IP of 1:1. Error bars: SEM. (C) Average reaction times for blocked (left) and patent fibers (right) as well as for laser-on (yellow) or laser-off (dark grey) trials. Offers are binned relative to the indifference point of a session (X-axis) as in (B) Average reaction times are in seconds (Y-axis, average of all sessions shown in (B). Error bars: SEM. See Figure 2—figure supplement 1 for breakdown of average behavior over the course of the experiment.
Figure 2—figure supplement 1
Average Effects of Medial Orbitofrontal Inactivation on the Economic Choice Divided into Three Epochs.
Average behavior on the choice task divided chronologically into three sets of sessions arranged in thirds from the early (top) to the late (bottom) part of the experiment. Results are shown for each condition: blocked and patent fibers (left and right respectively) and for laser-on and laser-off trials (yellow and grey curves respectively). Mean behavior was displayed by realigning the chosen offers from each session to the IP of that session before being averaged. Note that the two curves, laser-on and laser-off, are overlapping in most panels. The dark grey dotted line shows the average behavior expected if all sessions shifted to an IP of 1:1. Error bars: SEM.
Figure 3 with 1 supplement
Optogenetic Inhibition of Medial OFC during the Cue Period Does Not Affect the Indifference Point.
Histograms of the indifference points (IPs) from 50 sessions are shown for the blocked and patent fibers (A left/right), split by laser-on trials (yellow) and laser-off trials (grey). (B) A scatterplot showing the difference between same session laser-on and laser-off trials for paired blocked and patent fiber sessions (x- and y-axis respectively) with the corresponding histograms on each axis. (C) Boxplots of IPs for each treatment corresponding to the histograms in (A). To be sure that shifts in the indifference point were not masked by sessions with IPs near 1:1, sessions close to 1:1 were progressively removed using a sliding threshold (D). The average difference in IP for laser-on and -off trials were calculated only using sessions with IPs greater than the IP threshold (x-axis) for the blocked (grey) and patent (yellow) fiber sessions. The grey vertical line in (D) is the IP threshold corresponding to an IP significantly shifted from 1:1 (equal preference) as determined by a bootstrap method (see Materials and methods). All axes representing indifference points are plotted in log scale. See Figure 3—figure supplement 1 for comparison with virus control group.
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Figure 3—source data 1
Text File Containing the Source Data for Figure 3.
IP data is arranged as follows. Rows correspond to experimental replications. The first two columns (B-off and B-on) contain data for the blocked fiber with the laser-off and laser-on trials respectively. The latter two columns (P-off and P-on) contain data for the patent fiber with the laser-off and laser-on trials respectively.
- https://doi.org/10.7554/eLife.38963.007
Figure 3—figure supplement 1
Comparison of the Effects of Optogenetic Inhibition of Medial OFC on the Indifference Point with a Virus Control Group.
Indifference points (IPs) from 46 sessions in which rats were injected with a virus not containing the halorhodopsin gene in the nearby lateral orbitofrontal cortex (eYFP condition, n = 7, (A) left, data previously published [Gardner et al., 2017]) and 50 sessions from the current dataset (Halo condition, n = 6, (A) right, same data as in Figure 3) are shown for the blocked and patent patch cable fibers (A) top/bottom), split by laser-on trials (colored histograms) and laser-off trials (grey histograms). (B), Scatterplot of the paired within-session differences between laser-on and laser-off trials for each session-type (blocked and patent fibers, x- and y-axis respectively) bounded by corresponding histograms on each axis for the eYFP and Halo conditions (green and yellow respectively).
Figure 4 with 1 supplement
Optogenetic inhibition of medial OFC during the cue period does not affect the inverse slope.
Histograms of the inverse slope (, probit regression) from 50 sessions are shown for the blocked and patent fibers (A left/right), split by laser-on trials (yellow) and laser-off trials (grey). (B) A scatterplot showing the difference between same session laser-on and laser-off trials for paired blocked and patent fiber sessions (x- and y-axis respectively) with the corresponding histograms on each axis. (C) Boxplots of the inverse slope for each treatment corresponding to the histograms in (A). (D) The average difference in inverse slope for laser-on and -off trials calculated only using sessions with IPs greater than the IP threshold (x-axis) for blocked (grey) and patent (yellow) fibers. For this analysis sessions close to 1:1 were progressively removed to up to 90% of the total sessions analyzed. The grey vertical line in (D) is the IP threshold corresponding to an IP significantly shifted from 1:1 (equal preference) as determined by a bootstrap method (see methods). All axes representing indifference points are plotted in log scale. See Figure 4—figure supplement for comparison with virus control group.
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Figure 4—source data 1
Text File Containing the Source Data for Figure 4.
Slope data is arranged as follows. Rows correspond to experimental replications. The first two columns (B-off and B-on) contain data for the blocked fiber with the laser-off and laser-on trials respectively. The latter two columns (P-off and P-on) contain data for the patent fiber with the laser-off and laser-on trials respectively.
- https://doi.org/10.7554/eLife.38963.010
Figure 4—figure supplement 1
Comparison of the Effects of Optogenetic Inhibition of Medial OFC on the Slope with a Virus Control Group.
Estimates of the slope (, from 46 sessions in which rats were injected with a virus not containing the halorhodopsin gene in the nearby lateral orbitofrontal cortex (eYFP condition, n = 7, (A) left, data previously published [Gardner et al., 2017]) and 50 sessions from the current dataset (Halo condition, n = 6, (A) right, same data as in Figure 4) are shown for the blocked and patent patch cable fibers (A top/bottom), split by laser-on trials (colored histograms) and laser-off trials (grey histograms). (B) Scatterplot of the paired within-session differences between laser-on and laser-off trials for each session-type (blocked and patent fibers, x- and y-axis respectively) bounded by corresponding histograms on each axis for the eYFP and Halo conditions (green and yellow respectively).
Figure 5
Transitivity Is Unaffected by medial OFC Inactivation.
(A) Example of economic choice behavior from six sessions comprising one experimental unit of the test for transitivity. Sessions in each column show choice behavior between each pairing of three pellets referred to as (A, B, and C) based on decreasing order of preference (left: pair with the greatest IP - A vs C; middle: A vs B; right: B vs C). Top and bottom row show consecutive sessions, counterbalanced for order, in which the blocked or patent fiber, respectively, was used. Behavior is shown for both laser-on (yellow) and laser-off (trials) as well as the respective indifference point for each condition. (B), Transitivity plots are shown for the blocked (left) and patent (right) fiber types. Transitivity measures represent the consistency of food pellet preferences across six sessions in which animals experienced each of the possible pairs of three pellets (A–C,A–B,B–C) for both fiber-type conditions. Stable and consistent preferences should be in accordance with the relation: which can be visualized in the scatterplots as points falling close to the identity line. The Y- and X- axes show the IP, in log scale, for the pellet pair with the largest preference difference, , and the product of the IPs from the other two pairs (). The within-session pairs of laser-on trials (yellow symbols) and laser-off trials (grey symbols) are indicated by a dark grey line connecting the scatterplot pairs. Histograms comparing laser-on and -off trials are shown in the background for each of the plots. The six sessions shown in (A) are marked with a red outline on the respective scatter points in (B) Data is provided in Supplementary file 3 and Figure 5—source data 1. (C) The distances between within-session pairs (the lengths of the grey lines connecting the scatterplot pairs in (B) plotted as the cumulative empirical distribution function for each of the fiber-type conditions (blocked: yellow, patent: brown). For data see Figure 5—source data 1.
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Figure 5—source data 1
Text File Containing the Source Data for Figure 5 with the Same Layout as in Supplementary file 3.
SeeSupplementary file 3 for layout of data.
- https://doi.org/10.7554/eLife.38963.012
Figure 6
Confirmation of the Efficacy of Light to Inhibit Medial OFC Neurons Expressing Halorhodopsin in Slice Preparation.
(A) Example trace showing hyperpolarization caused by 10 s light exposure in an OFC neuron (left). Summary graphs showing effect of 10 s light exposure on membrane potential for both the initial peak and the steady state conditions (right). (B) Example traces showing effect of current injection in an OFC neuron. When current injection is given with light exposure, firing frequency decreases (left). Summary graph showing spikes elicited by a 400 pA current injection alone or with light exposure (middle). Summary graph showing the effect of light exposure on the number of spikes elicited per unit of injected current.
Figure 7
Confirmation of the Efficacy of medial OFC Inactivation on Behavior Using a Progressive Ratio Task.
In order to determine whether optogenetic inactivation of medial OFC was sufficient to affect behavior, we inactivated medial OFC on the progressive ratio task which has been previously shown to be disrupted with medial OFC using pharmalogical inactivation. (A) Rats which were used in the choice task learned to press a lever for food delivery, FR1 schedule, and then were run for four subsequent days on a progressive ratio five schedule (see Materials and methods for details) with the fiber-types counterbalanced in a fully balanced design. The average break point (Y-axis, left, top) is shown for blocked (grey) and patent fibers (yellow) as well as the individual data points. Black lines show paired sessions (first two or last two sessions) for the two runs of each animal. A histogram of the paired differences is shown in the bottom left panel. The right two panels show the average lever presses (top) and histogram of the differences in lever presses from paired sessions (bottom). (B) Histograms of the inter-press interval for the blocked and patent conditions (bin size = 0.5 s, top), and the cumulative distribution of the inter-press intervals (bottom). Insets show only the 0 – 10 s bins of the plots. (C) To determine whether medial OFC inactivation reduced rats’ motivation to consume pellets, we repeated the design used for the progressive ratio test, four consecutive days with fiber-types counterbalanced, while rats consumed pellets from a bowl for 30 min. Top panel shows the average pellets consumed over the 30 min (Y-axis) for each condition (blocked: grey, patent: yellow). Black lines show paired sessions (first two or last two sessions) for the two runs of each animal. A histogram of the paired differences is shown in the bottom panel. All bars represent mean ±SEM. *p<0.05 significance level.
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Strain, strain background (Rattus norvegicus) | Long-Evans Rat | Charles River | RRID: RGD_2308852 | |
| Transfected construct (Rattus norvegicus) | AAV5/CamKIIa-eNpHR3.0-eYFP | UNC Vector Core | ||
| Chemical compound, drug | DAPI-Fluorescent- G | Electron Microscopy Services | Cat No. 17984–24 | |
| Chemical compound, drug | Triton X-100 | Sigma-Aldrich | Cat No. X100- 500ML | |
| Software, algorithm | MATLAB | Mathworks | RRID: SCR_001622 | |
| Other | Doric dual optical commutators | Doric Lenses | Cat No. FRJ_1 × 2i_FC-2FC_0.22 | |
| Other | 200 micron diameter fiber optic patch cable | Thor Labs | M72L01 | |
| Other | Fiber optic cannulae | Thor Labs | Cat No. CFM12U- 20 | |
| Other | ceramic zirconia ferrule bore 230 um | Precision Fiber Products | Cat No MM- FER2002S15-P | |
| Other | FC multimode connector | Precision Fiber Products | Cat No. MM-CON2004-2300-2- BLK | |
| Other | 543 nm DPSS Laser | Shanghai Lasers | Cat No. GL543T3- 100 | |
| Other | Arduino Mega | Adafruit Industries | Cat No. 191 | |
| Other | 3.5’ Resistive Touch Screen | Adafruit Industries | Cat No. 2050 | |
| Other | Raspberry Pi 3 B | Adafruit Industries | Cat No. 3055 |
Additional files
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Supplementary file 1
Three-way ANOVA Results Comparing Medial OFC Inactivation with Behavioral Measures from a Virus Control Group.
- https://doi.org/10.7554/eLife.38963.015
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Supplementary file 2
Results of Two-Way ANOVA with Factors Laser and Fiber Performed on a Subset of Trials Taken from the Beginning of each Session.
- https://doi.org/10.7554/eLife.38963.016
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Supplementary file 3
Indifference Points for Sets of Transitivity Measures across Three Pellet-Types.
- https://doi.org/10.7554/eLife.38963.017
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Transparent reporting form
- https://doi.org/10.7554/eLife.38963.018
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Medial orbitofrontal inactivation does not affect economic choice
eLife 7:e38963.
https://doi.org/10.7554/eLife.38963
