Article Figures & Data
Figures
- Figure 1.
Calcium imaging fiber photometry reveals that NAc GABAergic neurons activate during spontaneous exploratory movement. A, Parasagittal section showing the optical fiber tract reaching NAc and GCaMP7f fluorescence expressed in GABAergic neurons around the fiber ending. The sections were aligned with the Allen Brain Atlas. The right panel depicts the range of fiber endings for photometry and optogenetic experiments. OT, olfactory tubercle; AON, anterior olfactory nucleus; SI, substantia innominata; BST, bed nucleus of stria terminalis; Str, dorsal striatum. B, Cross-correlation between movement and NAc F/Fo for the overall (black traces), rotational (red), and translational (blue) components top panel). Per session (dots) and mean ± SEM (rectangle) linear fit (correlation, r) between overall movement and NAc F/Fo, including the rotational and translational components (bottom panel). The lighter dots show the linear fits after scrambling one of the variables (bottom panel, shuffled). C, F/Fo calcium imaging time extracted around detected spontaneous movements. Time zero represents the peak of the movement. The top traces show F/Fo mean ± SEM of all movement peaks (black), those that had no detected peaks 3 s prior (red), and peaks taken at a fixed interval >5 s (cyan). The bottom traces show the corresponding movement speed for the selected peaks (n = 7 mice).
- Figure 2.
NAc GABAergic neurons code the direction of spontaneous contraversive exploratory turning movements. A, F/Fo calcium imaging, overall movement, rotational movement, and angle of turning direction for detected movements classified by the turning direction (ipsiversive and contraversive; red and cyan) versus the side of the recording (implanted optical fiber). At time zero, the animals spontaneously turn their head in the indicated direction. The columns show all turns (left), those that included no turn peaks 3 s prior (middle), and peaks selected at a fixed interval >5 s (right). Note that the speed of the movements was similar in both directions. B, Population measures (area of traces 3 s around the detected peaks) of F/Fo and movement (overall, rotational, and translational) for the different classified peaks. The measures that were different (p < 0.05) between ipsiversive and contraversive movements are indicated by * (n = 7 mice).
- Figure 3.
NAc GABAergic neurons discharge to auditory tones in association with movement. A, Example F/Fo calcium imaging and movement traces (mean ± SEM) evoked from NAc neurons by auditory tones (1 s) of different saliency. The tones vary in frequency (4–16 kHz) and SPL (low and high dB). B, Area of F/Fo, overall movement, and movement components (rotational and translational) measured during a time window (0–2 s) after the tone onset (n = 7 mice).
- Figure 4.
NAc GABAergic activation in the context of signaled active avoidance. A, Arrangement of the shuttle box used during signaled avoidance tasks. B, Behavioral performance during the four different avoidance procedures showing the percentage of active avoids (black circles), avoidance latency (orange triangles), and ITCs (cyan bars). C, F/Fo and overall movement traces from the CS onset for AA1, AA2, and AA3 (CS1 and CS2) procedures per trials classified as avoids (left) or escapes (right) of CS-evoked orienting responses measured by tracking overall head speed. D, Same as C from response occurrence. E, Population measures of F/Fo and speed for avoids and escapes during AA1, AA2, and AA3 (CS1). Asterisks denote p < 0.05 versus avoids (n = 7 mice).
- Figure 5.
NAc GABAergic neurons track the avoidance and escape movement. A, F/Fo and overall movement traces from the CS onset (left) and response occurrence (right) for avoids during the AA4 procedure, which include three CS’s that signal avoidance intervals of different durations. B, Population measures (−3 to 3 s area, mean ± SEM) from response occurrence. Asterisks denote significant differences versus other stimuli. C, F/Fo and overall movement traces from the US onset for escapes during the unsignaled US procedure, which includes the US, or each of its components delivered alone (footshock and white noise). D, Population measures (0–5 s area, mean ± SEM) for the data in C. Asterisks denote significant differences versus other CS's (n = 7 mice).
- Figure 6.
Optogenetic inhibition of NAc GABAergic neurons has little effect on signaled avoidance. A, B, Effect of Cont green light delivered at different powers on AA1/2 (A) and AA3 (B) in mice expressing eArch3.0 in NAc GABAergic neurons (n = 5 mice). C, Traces of overall movement (speed) during AA1 or AA2 for CS trials, and CS + light trials combined. The trials are aligned by the CS onset, which reveals the orienting response evoked by the CS followed by the ensuing avoid action. Note that CS + light trials suppress ongoing movement prior to the onset of the avoid action without impairing the ability to respond. D, Same as C but traces are aligned by the avoidance response occurrence, which reveals the peak speed of the response. Note that avoids are not different between CS and CS + light trials. As usual, AA2 produces faster avoids than AA1. E, Same as C but for AA3. CS1 and CS2 are control trials for active avoidance and passive avoidance, respectively. As per AA1 and AA2, ongoing movement is suppressed by the light. F, G, Same as A and B but for a control group of mice that do not express Arch in GABAergic NAc neurons as they were injected with an AAV targeting glutamatergic neurons. The light has negligible effects on AA1, AA2 (F), and AA3 (G; (n = 4 mice). H, I, Effect of blue light on Chat-Cre mice that express ChR2 in NAc cholinergic neurons. Patterns of blue light were applied into NAc during AA1 (H) and AA3 (I). The light caused negligible effects on the performance of the mice. CS trials are control trials without light. CS + light trials include the CS and light patterns (trains of 1 ms pulses at the noted frequencies in Hz or Cont). During AA3, CS1 trials are active avoidance trials (like CS trials in AA1/2), and CS2 trials are passive avoidance trials. The plots show the percentage of active avoids, the response latency, and the ITCs per trial. NoCS trials are catch trials without CS or consequence (n = 5 mice).
- Figure 7.
Lesions of NAc GABAergic neurons do not impair signaled avoidance learning or performance. A, Coronal NeuroTrace (green) stained section of a Vgat-Cre mouse injected with a Cre-dependent AAV-dtA in the NAc to kill GABAergic neurons. We counted the number of cells in the NAc in controls and lesion mice. There was a significant reduction in the number of NAc neurons in the lesion mice. B, Behavioral performance during learning of AA1, followed by AA2 and AA3 procedures showing the percentage of active avoids (top), avoid latency (middle), and ITCs (bottom) for control and lesion mice. The AA3 procedure shows CS1 and CS2 trials for the same sessions. Active avoids during AA3-CS2 trials are errors, as the mice must passively avoid during CS2. Lesion mice tended to have shorter avoid latencies, but as is usual both control and lesion mice shifted their avoid latencies longer during AA2 compared with AA1 (n = 9 lesion mice; n = 6 control mice). C, Movement (speed) from the CS onset (left) and from avoid occurrence (right) during AA1 and AA2 procedures for control and lesion mice. The lesion had little effect on movement other than the tendency to shift avoid movement sooner. However, the overall avoid speed measured from response occurrence was not faster in lesion mice. As typically observed in controls, lesion mice avoided faster during AA2 compared with AA1. D, Same as C for AA3. E, Population measures of orienting, avoidance, and escape responses from the CS onset (left) and from response occurrence (right) for overall movement. F, Bilateral electrolytic lesions targeting the NAc. G, Effect of bilateral electrolytic NAc lesions on behavioral performance in a RM design. The plot shows the percentage of active avoids (filled black circles), avoid latency (open orange squares), and ITCs (cyan bars). Mice were trained in AA1 prior to the lesion and then placed back in AA1, followed by AA2 and AA3. The main effect of the lesion was to increase the number of ITCs during AA1, with little negative effect on active avoids. During AA2, lesion mice normally abolished their ITCs, which are punished, and shifted avoid latencies longer with little effect on avoidance performance. During AA3, lesion mice also performed AA3 normally, actively avoiding during CS1 and passively avoiding during CS2 (n = 9 lesion mice).
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