Central amygdala activity during fear conditioning

Abstract

The central amygdala (Ce), particularly its medial sector (CeM), is the main output station of the amygdala for conditioned fear responses. However, there is uncertainty regarding the nature of CeM control over conditioned fear. The present study aimed to clarify this question using unit recordings in rats. Fear conditioning caused most CeM neurons to increase their conditioned stimulus (CS) responsiveness. The next day, CeM cells responded similarly during the recall test, but these responses disappeared as extinction of conditioned fear progressed. In contrast, the CS elicited no significant average change in central lateral (CeL) firing rates during fear conditioning and a small but significant reduction during the recall test. Yet, cell-by-cell analyses disclosed large but heterogeneous CS-evoked responses in CeL. By the end of fear conditioning, roughly equal proportions of CeL cells exhibited excitatory (CeL(+)) or inhibitory (CeL(-)) CS-evoked responses (∼10%). The next day, the proportion of CeL(-) cells tripled with no change in the incidence of CeL(+) cells, suggesting that conditioning leads to overnight synaptic plasticity in an inhibitory input to CeL(-) cells. As in CeM, extinction training caused the disappearance of CS-evoked activity in CeL. Overall, these findings suggest that conditioned freezing depends on increased CeM responses to the CS. The large increase in the incidence of CeL(-) but not CeL(+) cells from conditioning to recall leads us to propose a model of fear conditioning involving the potentiation of an extrinsic inhibitory input (from the amygdala or elsewhere) to CeL, ultimately leading to disinhibition of CeM neurons.

Figure 1.

Histological identification of recording sites. Coronal sections of the rat amygdala with electrolytic lesions performed at the end of the experiments to mark the recording sites. A, B, The depicted cases show examples of lesions in CeM (A) and CeL (B). BL, Basolateral nucleus of the amygdala; EC, external capsule; Str, striatum.

Figure 2.

The CS responsiveness of CeM neurons increases as a result of fear conditioning. A, Time (average ± SEM) rats (n = 33) spent freezing during the CS in various phases of the behavioral protocol (x-axis). Color-coded symbols indicate the CSs used to average the activity of CeM neurons in B–D. B, C, Peri-CS fluctuations in the firing rates of CeM neurons (5 s bins) on days 1 (B) and 2 (C). Average and ±SEM are shown by solid and dashed lines, respectively. 1, Average of all CeM cells. 2, Average of a subset of CeM cells with significant (p ≤ 0.05) increases in activity during the CS. 3, Activity of the cells used to obtain the averages of 2. D, Frequency distribution of z-scored changes in CS responsiveness on day 1 (D1) and day 2 (D2).

Figure 3.

CS responsiveness of CeL neurons. A, B, Peri-CS fluctuations in the firing rates of CeL neurons (5 s bins) on days 1 (A) and 2 (B). The same color code is used as in Figure 1. Average and ±SEM are shown by solid and dashed lines, respectively. 1, Average of all CeL cells. 2, Average of subsets of CeL cells with significantly (p ≤ 0.05) increased or decreased activity during the CS. 3, 4, Activity of the cells used to obtain the averages of 2. C, Frequency distribution of z-scored changes in CS responsiveness on day 1 (C1) and day 2 (C2).