Amygdalar lesions block discriminative avoidance learning and cingulothalamic training-induced neuronal plasticity in rabbits

Abstract

Learning to fear dangerous situations requires the participation of neurons of the amygdala. Here it is shown that amygdalar neurons are also involved in learning to avoid dangerous situations. Amygdalar lesions severely impaired the acquisition of acoustically cued, discriminative instrumental avoidance behavior of rabbits. In addition, the development of anterior cingulate cortical and medial dorsal thalamic training-induced neuronal plasticity in the early stages of behavioral acquisition was blocked in rabbits with lesions. The development of training-induced neuronal plasticity in the medial dorsal and anterior thalamic nuclei in late stages of behavioral acquisition was also blocked in rabbits with lesions. These results indicate that the integrity of the amygdala is essential for the establishment of both early and late training-induced cingulothalamic neuronal plasticity. It is hypothesized that amygdalar training-induced neuronal plasticity in the initial trials of conditioning represents a substrate of learned fear, essential for the early and late cingulothalamic plasticity that is involved in mediation of acquisition of the instrumental avoidance response.

Fig. 1.

Schematic coronal sections at three AP levels of the rabbit brain: bregma (AP 0), 1.5 mm posterior to bregma (AP +1.5), and 2.0 mm posterior to bregma (AP +2.0). The largest and smallest amygdalar lesions are shown, respectively, by the hatched and dark areas. The corresponding schematic sections in the lower part of the figure portray the central (CE), lateral–anterior (LA), basolateral (BL), basomedial (BM), medial (ME), cortical (CO), lateroposterior (LP), and basal accessory (BA) amygdalar areas.

Fig. 2.

Percentage of conditioned responses performed in response to the CS+ during each daily training session (day) for controls (n = 15), lesioned rabbits that learned (n = 3), and lesioned rabbits that did not learn (n = 5). Training was terminated for the lesioned rabbits that did not reach significant behavioral discrimination (see text) by the seventh training day. The plotted scores for the control group exclude data of one rabbit that did not learn.

Fig. 3.

Scatter plots of the percentage of conditioned response and the percentage of lesion-induced brain damage in the central, lateral, and basolateral amygdalar nuclei of the rabbits with lesions. The regression line represents the prediction ofy (conditioned responses) from x (brain damage). The corresponding Pearson product–moment correlations are shown in the top right corner of each plot.PT, pretraining; FE, first exposure to conditioning; FS, first significant discrimination;CRIT, criterion attainment.

Fig. 4.

Average multiunit neuronal activity of the AV thalamic nucleus (left two columns), MD thalamic nucleus (middle two columns), and anterior cingulate cortex in response to CS+ (dark bars) and CS− (open bars) presented to rabbits with sham lesions (top row, Control) and amygdala lesions (bottom row, Lesion). The bars in each panel represent the neuronal activity in the form of z scores (see text) in 40 consecutive 10 msec intervals after the onset of the CS+ and CS−. The first, third, and fifth columnsrepresent the neuronal activity recorded during the preliminary training session in which the tones that would be used as CS+ and CS− and the foot shock were presented in an explicitly unpaired manner (neither tone predicted the foot shock). The second, fourth, and sixth columns show the neuronal activity recorded during the training session in which the acquisition criterion was attained by rabbits with sham lesions or (for rabbits that did not reach the criterion) during their last training session.

Fig. 5.

Schematic depiction of the brain structures that mediate the processes necessary for discriminative avoidance learning. Amygdalar efferents depicted by the arrow on theleft are involved in establishment of early developing cingulothalamic discriminative plasticity. Amygdala efferents depicted by the obliquely angled arrows are involved in establishment of late-developing cingulothalamic discriminative plasticity. US, Unconditioned stimulus.