Article Figures & Data
Figures
- Figure 1.
A, Experimental timeline. B, Rats received 12-d homecage intermittent access to EtOH. Consumption escalated significantly over days. C, Operant task diagram. Rats nosepoked to receive cues predicting sucrose or EtOH. Outcomes were consumed by licking a spigot in a reward port below the nosepoke. D, Rats acquired significantly more sucrose (blue) than 10% EtOH (purple) or 20% EtOH (red) rewards. E, Rats consumed significantly more sucrose than 20% EtOH based on duration of reward consumption; *p < 0.05, **p < 0.01, ****p < 0.0001.
- Figure 2.
A, Recording sites in the OFC (black circles) based on lesions made postrecording. B, Example activity from OFC neuron recorded during a sucrose session. Rasters (bottom) and 50-ms bin histogram (top) show the prominent inhibition during cue presentation followed by excitation during reward seeking and inhibition during reward consumption. C, Z-scored average OFC activity with standard error confidence intervals (CIs) across all neurons aligned on cue presentation in sucrose (blue CI), 10% EtOH (purple CI), and 20% EtOH (red CI) sessions. D, Numbers of neurons significantly excited or inhibited during each epoch in sucrose (blue), 10% EtOH (purple), and 20% EtOH (red) sessions.
- Figure 3.
Index calculations for individual OFC neuron activity during cue presentation (left column), reward seeking (middle column), and reward consumption (right column) during sucrose (top row), 10% EtOH (middle row), and 20% EtOH (bottom row) sessions. Indices calculated as in Materials and Methods. Beh = behavioral epoch; Base = baseline epoch. NS not significant; **p < 0.01, ***p < 0.001, ****p < 0.0001.
- Figure 4.
Rats were separated into HDs and LDs based on homecage EtOH consumption (see Materials and Methods). A, HD rats exhibited significant escalation over the course of homecage intermittent access to EtOH whereas LD rats did not. B, HD rats (filled bars) completed significantly more rewarded trials for 20% EtOH (red) than LD rats (open bars), but there were no differences for sucrose (blue) or 10% EtOH (purple) rewarded trials. C, HD rats consumed significantly more 20% EtOH than LD rats, measured by lick duration, but there were no differences in consumption of sucrose or 10% EtOH. D, OFC neuronal activity in HD versus LD rats was similar during sucrose cues, seeking, and consumption but was significantly different during cues, seeking, and consumption of 10% EtOH (E) and during cues and seeking of 20% EtOH (F). Overall strength of OFC signaling (either excitation or inhibition) was suppressed in LD rats relative to HD rats in EtOH sessions; *p < 0.05, **p < 0.01, ***p < 0.001.
- Figure 5.
OFC neuronal activity was recorded during interleaved trials of 20% EtOH and sucrose. A, During interleaved sessions, HD (filled bars) and LD (open bars) rats completed similar numbers of sucrose (blue) and 20% EtOH (red) trials. B, However, LD rats consumed significantly less 20% EtOH than HD rats. C, Example of activity from a single neuron in sucrose (top) and 20% EtOH (bottom) conditions. D–F, Sucrose/EtOH index profiles for individual neurons recorded during interleaved trials of sucrose and 20% EtOH seeking. Recording the same neuron in both conditions allowed characterization of sucrose/EtOH index profiles for each neuron. Indices were calculated as in blocked conditions. Each dot represents sucrose/20% EtOH index combination for each neuron during cue (D, n = 156 neurons), seeking (E, n = 137 neurons), and reward (F, n = 137 neurons). Only neurons in which seeking and consumption trials were performed for both sucrose and 20% EtOH were included in seeking and reward plots; r and p values indicate significant correlations across all neurons in sucrose and EtOH trials, despite a bias toward significant selectivity in encoding of one versus another outcome. Blue, red, black, and gray dots represent neurons significantly activated/inhibited during sucrose conditions only, 20% EtOH only, both, and neither condition, respectively. Although a subset of neurons exhibited significant modulation in both sucrose and EtOH trials (black dots: 8 in response to cue, 17 during seeking, and 29 during consumption), the majority of significantly-influenced neurons exhibited selectivity for sucrose (blue dots: 14 cue, 16 seeking, and 58 consumption) or EtOH (red dots: 15 cue, 22 seeking, and 19 consumption). Numbers in each quadrant indicate numbers of neurons falling within that quadrant. Neurons with an index of 0 in one axis were not counted in quadrant totals. Most neurons showed inhibition during sucrose and EtOH cues, excitation during sucrose and EtOH seeking, and inhibition during sucrose and EtOH consumption, in line with patterns observed during blocked conditions. G, H, OFC activity was similar in sucrose (G) and 20% EtOH (H) trials in HD rats, but activity of OFC neurons in LD rats was again suppressed relative to activity of those in HD rats. This was true for neuronal responses to the cue, during reward seeking, and during sucrose/EtOH consumption; **p < 0.01, ***p < 0.001, ****p < 0.0001.
Tables
- Table 1
Distribution of response profiles across neurons during blocked sucrose, 10% EtOH, and 20% EtOH recording sessions
Sucrose 10% EtOH 20% EtOH Cue Seeking Reward # Ns Cue Seeking Reward # Ns Cue Seeking Reward # Ns 0 1 –1 43 0 0 –1 37 –1 0 0 20 0 0 –1 30 –1 1 0 17 0 0 –1 11 –1 –1 –1 20 0 1 –1 7 1 0 0 10 0 –1 –1 16 –1 0 –1 5 0 0 1 9 0 1 0 12 –1 –1 0 4 0 1 0 9 1 0 0 8 –1 1 –1 2 1 1 1 8 –1 0 1 4 –1 0 0 1 0 1 1 5 –1 1 –1 4 0 –1 –1 1 0 –1 1 4 –1 0 –1 3 1 0 0 1 1 0 –1 3 –1 1 0 2 1 1 0 1 –1 0 –1 2 0 –1 0 2 1 0 1 2 –1 0 0 1 –1 –1 1 1 0 0 1 1 1 –1 1 1 0 1 1 1 1 0 –1 1 0 0 0 14 0 0 0 18 0 0 0 50 Neuron populations are ordered from those containing most to least members. Category of response to cue, seeking, or reward is demarcated by −1 (significant inhibition during that epoch), +1 (significant excitation during that epoch), or 0 (no significant activity during that epoch). At the bottom of each section is the number of non-responsive neurons [0,0,0]. Any combination of responses not shown in this table was not observed during recording.
- Table 2
Distribution of response profiles across neurons during interleaved sucrose, 10% EtOH, and 20% EtOH recording sessions
Sucrose 20% EtOH Cue Seeking Reward Cue Seeking Reward # Ns 0 0 –1 0 0 0 28 0 0 –1 0 1 0 10 0 0 –1 0 0 –1 9 0 1 –1 0 0 0 8 0 0 0 0 1 1 4 1 1 1 1 1 1 4 0 0 –1 –1 1 0 3 0 1 –1 0 0 –1 3 0 1 0 0 1 0 3 –1 0 –1 –1 0 0 2 –1 0 –1 0 0 –1 2 0 0 –1 –1 0 –1 2 0 0 –1 –1 0 0 2 0 0 –1 0 1 1 2 0 0 1 0 0 1 2 0 1 –1 0 1 0 2 1 0 0 0 0 1 2 1 0 0 1 0 1 2 1 1 0 1 1 1 2 –1 0 –1 –1 0 –1 1 –1 0 0 –1 0 0 1 –1 0 0 0 0 0 1 –1 0 0 0 0 1 1 0 –1 –1 –1 –1 0 1 0 –1 –1 –1 0 0 1 0 –1 –1 0 0 –1 1 0 –1 0 0 –1 –1 1 0 –1 0 0 0 –1 1 0 –1 0 1 –1 –1 1 0 –1 1 0 –1 –1 1 0 0 0 –1 0 0 1 0 0 0 0 –1 –1 1 0 0 0 0 0 –1 1 0 0 0 0 0 1 1 0 0 0 0 1 0 1 0 1 –1 0 1 1 1 0 1 0 0 1 1 1 0 1 0 1 0 0 1 1 0 0 0 0 0 1 1 1 0 0 0 0 1 1 1 0 0 1 1 1 1 1 1 0 1 1 1 0 0 0 0 0 0 19 Format is the same as Table 1, except that the same neurons were recorded in sucrose/20% EtOH interleaved sessions and neurons are categorized based on responses in both trial types.
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