The role of amygdala nuclei in the expression of auditory signaled two-way active avoidance in rats

Abstract

Using a two-way signaled active avoidance (2-AA) learning procedure, where rats were trained in a shuttle box to avoid a footshock signaled by an auditory stimulus, we tested the contributions of the lateral (LA), basal (B), and central (CE) nuclei of the amygdala to the expression of instrumental active avoidance conditioned responses (CRs). Discrete or combined lesions of the LA and B, performed after the rats had reached an asymptotic level of avoidance performance, produced deficits in the CR, whereas CE lesions had minimal effect. Fiber-sparing excitotoxic lesions of the LA/B produced by infusions of N-methyl-d-aspartate (NMDA) also impaired avoidance performance, confirming that neurons in the LA/B are involved in mediating avoidance CRs. In a final series of experiments, bilateral electrolytic lesions of the CE were performed on a subgroup of animals that failed to acquire the avoidance CR after 3 d of training. CE lesions led to an immediate rescue of avoidance learning, suggesting that activity in CE was inhibiting the instrumental CR. Taken together, these results indicate that the LA and B are essential for the performance of a 2-AA response. The CE is not required, and may in fact constrain the instrumental avoidance response by mediating the generation of competing Pavlovian responses, such as freezing.

Figure 1.

Acquisition of the avoidance response. Data were averaged from animals that had reached the learning criterion on day 5 (<80% avoidance CR, n = 16). (A) Day-to-day changes in avoidance CR rate. (B) Corresponding freezing and ultrasonic vocalizations (USVs) measured from the 15-sec pre-CS period on every trial.

Figure 2.

Histological reconstruction of amygdala subnuclei lesions. The black regions indicate the least extensive lesion, and the gray regions indicate the most extensive lesion. In the leftmost column, the numbers indicate the distance in millimeters from the bregma. AMG, entire amygdala; L, LA, lateral nucleus; B, basal nucleus; C, CE, central nucleus; Bm, basomedial nucleus. Brain images were adapted from Paxinos and Watson (1998) and reprinted here with permission from Elsevier © 1998.

Figure 3.

Effects of amygdala subnuclei lesions on avoidance response. (A) Comparison of avoidance CR rates on the last day of training (Before Surgery) and on the first and second day of postsurgical training (Day 1 and Day 2). (B) Comparison of avoidance CR latencies on the last day of training and on the first and second day of postsurgical training. Numbers of subjects included in the analysis were: SHAM = 10; AMG = 9; LA/B = 9; LA = 9; B = 8; CE = 9. An asterisk (*) indicates statistically significant difference from the SHAM group.

Figure 4.

Histological lesion reconstruction for NMDA-lesioned animals. The dark gray areas indicate the lesion size in the least extensive lesioned animal, and the lighter gray areas are from the most extensive lesioned animal. In the leftmost column, numbers indicate the distance in millimeters from the bregma. See Figure 1 for anatomical notations of the amygdala subnuclei. Brain images were adapted from Paxinos and Watson (1998) and reprinted here with permission from Elsevier © 1998.

Figure 5.

Photomicrographs of representative SHAM and chemical lesions in the LA and B. (A) SHAM-lesion, (B) NMDA lesion.

Figure 6.

Effect of NMDA lesions on the avoidance response. (A) Comparison of avoidance CR rates. (B) Comparison of avoidance latencies. An asterisk (*) indicates statistically significant difference from the SHAM group. Numbers of subjects included in the analysis were: SHAM = 9; Lesion = 9.

Figure 7.

Effect of CE lesions on retarded avoidance learning. Rats with an avoidance CR rate of 20% or below for 3 consecutive days from the beginning of training were subjected to either a SHAM operation or an electrolytic CE lesion. The graph shows performance in avoidance learning for 3 d before and 5 d after the surgery. Numbers of subjects included in the final analysis were: Sham = 6; CE Lesion = 7.