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Conditioned fear inhibits c-fos mRNA expression in the central extended amygdala - PubMed

Heidi E W Day  1 ,

Conditioned fear inhibits c-fos mRNA expression in the central extended amygdala

Heidi E W Day et al. Brain Res. .

Abstract

We have shown previously that unconditioned stressors inhibit neurons of the lateral/capsular division of the central nucleus of the amygdala (CEAl/c) and oval division of the bed nucleus of the stria terminalis (BSTov), which form part of the central extended amygdala. The current study investigated whether conditioned fear inhibits c-fos mRNA expression in these regions. Male rats were trained either to associate a visual stimulus (light) with footshock or were exposed to the light alone. After training, animals were replaced in the apparatus, and 2 h later injected remotely, via a catheter, with amphetamine (2 mg/kg i.p.), to induce c-fos mRNA and allow inhibition of expression to be measured. The rats were then presented with 15 visual stimuli over a 30 minute period. As expected, fear conditioned animals that were not injected with amphetamine, had extremely low levels of c-fos mRNA in the central extended amygdala. In contrast, animals that were trained with the light alone (no fear conditioning) and were injected with amphetamine had high levels of c-fos mRNA in the CEAl/c and BSTov. Animals that underwent fear conditioning, and were re-exposed to the conditioned stimulus after amphetamine injection had significantly reduced levels of c-fos mRNA in both the BSTov and CEAl/c, compared to the non-conditioned animals. These data suggest that conditioned fear can inhibit neurons of the central extended amygdala. Because these neurons are GABAergic, and project to the medial CEA (an amygdaloid output region), this may be a novel mechanism whereby conditioned fear potentiates amygdaloid output.

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Figures

Figure 1

Experiment 1: Relative levels of c-fos mRNA in the BSTov and CEA. Animals either remained in their home cages within the colony room (Control) or were exposed to footshock, under the same paradigm used for the fear conditioning procedure (Experiment 2), on 2 consecutive days (Shock), before injection with amphetamine, 2 mg/kg i.p., in a different environment the following day. Amphetamine administration resulted in strong c-fos mRNA expression in both the BSTov and CEA, but previous shock experience did not diminish this expression in either brain region.

Figure 2

Experiment 2: Startle response amplitudes (% baseline) to a 95dB or 100 dB noise burst, co-terminating with a 3.7 s light stimulus in (i) animals with no previous light-shock association (control group) and (ii) animals which had been trained to associate the light with a 0.6 mA, 0.5 s footshock (fear conditioned group). Data are expressed as a percentage of baseline startle, which was taken as the mean startle response to the previous 3 noise burst stimuli at either 95 dB or 100 dB as appropriate. * p < 0.01 with respect to the control group.

Figure 3

Experiment 2: Relative levels of c-fos mRNA in the BSTov and CEA. Animals were trained to associate a 3.7 s light (L) with a 0.6 mA, 0.5 s footshock (S), or were exposed to the light (L) but did not receive shock (−). On the test day animals were either re-exposed to the light (L) or the startle apparatus alone (−), and either received amphetamine (A; 2 mg/kg i.p.) via the i.p. catheter, or no injection (−). The no injection animals served as a control for c-fos mRNA expression elicited by a conditioned fear stimulus alone. * p < 0.05, ** p < 0.01, *** p < 0.001 with respect to the fear conditioned group that did not receive an amphetamine injection (Train L/S; Test L/-). † p < 0.05 with respect to control animals that did not undergo fear conditioning, and received amphetamine on the test day (Train L/−; Test L/A).

Figure 4

Experiment 2: Photographs of x-ray films showing the expression of c-fos mRNA in the BSTov (A, B, C) and CEA (D, E, F) 30 minutes after (A,D) the presentation of 15 conditioned light stimuli, but with no amphetamine injection (Group 1: animals had been trained to associate the light stimuli with foot shock), (B,E) amphetamine injection, 2 mg/kg i.p. plus the presentation of 15 unconditioned light stimuli (Group 2: animals had been exposed to the visual stimuli alone, without footshock), (C,F) amphetamine injection, 2 mg/kg i.p. plus the presentation of 15 conditioned light stimuli (Group 3: animals had been trained to associate the light stimuli with foot shock).

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