Article Figures & Data
Figures
- Figure 1.
LHb inactivation before threat and extinction training does not affect learning and memory. A1, B1, left, Schematic representation of rats training. Rats were infused with SAL or M&B into LHb (gray arrow) before being trained to associate a tone with foot-shocks (day 1; Cond, conditioning). This training represents threat learning (red). One day later, rats were trained to associate the same tone with the absence of foot-shocks (day 2; Ext, extinction), which represents safety learning (green). Finally, the next day, rats were presented with tones only (day 3, test), which involves the retrieval competition of coexisting threat (red) and safety (green) memories to control defensive responses. Right, Coronal drawings of rat brain atlas showing placements of the injector tips in LHb. A2, LHb inactivation before threat conditioning (day 1; gray arrow and shaded area in graph), did not affect threat learning (day 1) or its memory formation (day 2), as indicated similar levels of tone-elicited freezing and lever-press suppression ratio [inset; late conditioning (last two-tone trial block), early extinction (first two-tone trial block), and test] between groups (SAL, n = 5; M&B, n = 7). B2, Infusion of M&B into LHb before extinction training (day 2; gray arrow and shaded area in graph), did not affect, expression of threat memory (day 2), safety learning (day 2) or its memory formation (day 3), as indicated by similar levels of percent freezing and lever-press suppression ratio [inset, late conditioning (last two-tone trial block), early extinction (first two-tone trial block), and test] between groups (SAL, n = 11; M&B, n = 9). Data are shown as ±SEM in blocks of two trials. LHb, lateral habenula. Inf, infusion. Supp. ratio, suppression ratio; x, baseline (pretone) freezing levels.
- Figure 2.
LHb inactivation before memory test, after extinction, abolishes defensive responses. A1, left, Schematic representation of rats training. Rats were trained to associate tones with foot-shocks (day 1; Cond, conditioning), which represents threat learning (red). One day later, rats were trained to associate the same tone with the absence of foot-shocks (day 2; Ext, extinction), which represents safety learning (green). Finally, the next day, rats were infused with SAL or M&B into LHb (gray arrow) before being presented with tones only (day 3, test), which involves the retrieval competition of coexisting threat (red) and safety (green) memories to control defensive responses. Right, Coronal drawings of rat brain atlas showing placements of the injector tips in LHb. A2, LHb inactivation before retrieval test (day 3), after extinction (gray arrow and shaded area in graph), decreased defensive responses, as indicated by lower levels of tone-elicited percent freezing and lever-press suppression ratio [inset; late conditioning (last two-tone trial block), early extinction (first two-tone trial block), and test] in the experimental group as compared with the control groups (SAL, n = 7; miss M&B, n = 8; hit M&B, n = 9). Data are shown as ± SEM in blocks of two trials. LHb, lateral habenula. Inf, infusion. Supp. ratio, suppression ratio; x, baseline (pretone) freezing levels; *p < 0.05.
- Figure 3.
LHb inactivation effect is extinction-dependent and not attributable to impairments in locomotion or other emotional behaviors. A1, left, Schematic representation of rats training. Rats were trained to associate a tone with foot-shocks (day 1; Cond, conditioning), which represents threat learning (red). One day later, rats were put back in the conditioning chamber (day 2; No Ext, no tone extinction). The next day, rats were infused with SAL or M&B into LHb (gray arrow) before being presented with tones only (day 3, test), which represents the retrieval of the threat-related memory (red). Right, Coronal drawings of rat brain atlas showing placements of the injector tips in LHb. A2, LHb inactivation before retrieval test (day 3) without extinction (gray arrow and shaded area in graph), did not affect defensive responses to the tone, as indicated by similar levels of tone-elicited percent freezing and lever-press suppression ratio (inset, late conditioning; last two-tone trial block and test) between control and experimental groups (SAL, n = 8; M&B, n = 6). Data are shown as ±SEM in blocks of two trials. Supp. ratio, suppression ratio; x, baseline (pretone) freezing levels. B1, left, Schematic representation of open field task. Right, Coronal drawings of rat brain atlas showing the placements of the injector tips in LHb. B2, LHb inactivation did not affect locomotion or anxiety-related behavior, as indicated by similar distance traveled and number of entries to the center of the field (SAL, n = 12; M&B, n = 11). C1, left, Schematic representation of lever pressing. Right, Coronal drawings of rat brain atlas showing the placements of the injector tips in LHb. C2, LHb inactivation did not affect reward-seeking behavior, as indicated by similar presses per minute to obtain food (SAL, n = 5; M&B, n = 7). LHb, lateral habenula. Inf, infusion.
- Figure 4.
LHb inactivation before retrieval test, after conditioned latent inhibition, abolishes defensive responses. A1, Schematic representation of rats training. Rats were either presented with tones (latent inhibition group: LI), which represents safety learning (green), or simply placed in the conditioning chamber (no-latent inhibition group: No-LI; day 1; Pre-exp, preexposure). One day later, both groups were placed in the same behavioral chamber and trained to associate a tone with foot-shocks (day 2; Cond, conditioning), which represents threat learning (red). Finally, the next day, were presented with tones only (day 3, test), which involves the retrieval competition of coexisting safety (green) and threat (red) memories to control defensive responses. A2, Tone preexposure weakened subsequent threat learning, as indicated by lower tone-elicited percent freezing and lever-press suppression ratio (inset; late preexposure, early conditioning, and test) levels of the LI group, as compared with No-LI group at the beginning of conditioning (No-LI, n = 11; LI, n = 12). B1, left, Schematic representation of rats training. Rats were pre exposed to tones alone (day 1; Pre-exp, preexposure), which represents safety learning (green). One day later, rats were trained to associate the tone with foot-shocks (day 2; Cond, conditioning), which represents threat learning (red). Finally, the next day, rats were infused with SAL or M&B into LHb (gray arrow) before being presented with tones only (day 3, test), which involves the retrieval competition of coexisting safety (green) and threat (red) memories to control defensive responses. Right, Coronal drawings of rat brain atlas showing placements of the injector tips in LHb. B2, LHb inactivation before retrieval test (day 3), after latent inhibition and conditioning (gray arrow and shaded area in graph), decreased defensive responses as indicated by lower levels of tone-elicited percent freezing and lever-press suppression ratio [inset; late conditioning (last two-tone trial block), early extinction (first block of trails), and test] in the experimental group as compared with the control group (SAL, n = 8; M&B, n = 5). Data are shown as ±SEM in blocks of two trials. LHb, lateral habenula. Inf, infusion. Supp. ratio, suppression ratio; x, baseline (pretone) freezing levels; *p < 0.05.
- Figure 5.
LHb inactivation before PMA retrieval test biases choice-mediated defensive behavior toward reward-seeking. A, left, Schematic representation of rats training. Rats were trained to associate tone with foot-shocks as well as associating the tone with moving to a safety platform learn to avoid the shock (day 1–10; PMA). Early PMA (day 2) represents classical conditioned-mediated threat learning (red), whereas late PMA (day 10) represents instrumental avoidance-mediated safety learning (green). One day later, rats were infused with SAL or M&B into LHb (gray arrow) before being presented with tones only (day 11, test), which involves the retrieval competition of coexisting threat (red) and safety (green) memories to control choice behavior. Right, Coronal drawings of rat brain atlas showing placements of the injector tips in LHb. B, During early PMA training (day 2), freezing and avoidance levels are similar. In contrast, during late PMA training (day 10), avoidance levels are higher than freezing levels. Thus, avoidance levels dramatically increased with PMA training while freezing levels remain similar (n = 15). C, LHb inactivation before PMA test (gray arrow and shaded area in graph), impaired retrieval of PMA memory, as indicated by lower tone-elicited percent freezing responses (but not suppression ratio) of the experimental group as compared with control group (SAL, n = 7; M&B, n = 8). D, LHb inactivation before PMA test (gray arrow) biased choice-mediated avoidance toward reward-seeking behavior as indicated by lower tone-elicited percent avoidance (D1) and time spent in platform (D2), as well as lower suppression ratio (inset) in the experimental group as compared with the control group (SAL, n = 7; M&B, n = 8). Data are shown as ±SEM in blocks of two trials in B, C, D1 and in 6-s bins in D2. LHb, lateral habenula. Inf, infusion. Supp. ratio, suppression ratio; ****p < 0.00001, *p < 0.05.
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