Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Dec 5:7:191.
doi: 10.3389/fnbeh.2013.00191.

Differential activation of amygdala Arc expression by positive and negatively valenced emotional learning conditions

Affiliations
Review

Differential activation of amygdala Arc expression by positive and negatively valenced emotional learning conditions

Erica J Young et al. Front Behav Neurosci. .

Abstract

Norepinephrine is released in the amygdala following negatively arousing learning conditions. This event initiates a cascade of changes including the transcription of activity-regulated cytoskeleton-associated protein (Arc) expression, an early-immediate gene associated with memory encoding. Recent evidence suggests that the valence of emotionally laden encounters may generate lateralized, as opposed to symmetric release of this transmitter in the right or left amygdala. It is currently not clear if valence-induced patterns of selective norepinephrine output across hemispheres are also reproduced in downstream pathways of cellular signaling necessary for memory formation. This question was addressed by determining if Arc expression is differentially distributed across the right and left amygdala following exposure to positively or negatively valenced learning conditions respectively. Male Sprague Dawley rats were randomly assigned to groups exposed to the Homecage only, five auditory tones only, or five auditory tones paired with footshock (0.35 mA) during Pavlovian fear conditioning. Western blot analysis revealed that Arc expression in the right amygdala was elevated significantly above that observed in the left amygdala 60 and 90 min following fear conditioning. Similarly, subjects exposed to a negatively valenced outcome consisting of an unexpected reduction in food rewards showed a greater level of Arc expression in only the right, but not left basolateral amygdala. Presenting a positively valenced event involving an unexpected increase in food reward magnitude following bar pressing, resulted in significantly greater Arc expression in the left, but not right basolateral amygdala (p < 0.01). These findings indicate that the valence of emotionally arousing learning conditions is reflected at later stages of synaptic plasticity involving the transcription of immediate early genes such as Arc.

Keywords: Arc expression; amygdala; amygdala lateralization; brain asymmetry; emotional arousal; memory modulation.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The boxed square represents the area of interest between −2.6 and −3.2 from Bregma selected for quantification of Arc signal in the right and left basolateral amygdala after Pavlovian Fear Conditioning (Experiments 1 and 2) or Appetitive Training with positive or negative reinforcement contingencies (Experiment 3).
Figure 2
Figure 2
Mean (+SE) percentage of time freezing during Pavlovian conditioning with a 30 s tone CS that coterminated with a 1 s 35 mA footshock. Subjects in the Fear Conditioning group displayed significantly more freezing during the final three tone presentations than controls in the Tone Only Group (Fear Conditioning 30 min vs. Tone Only, p < 0.01; Fear Conditioning 60 min vs. Tone Only, p < 0.01; Fear Conditioning 90 min vs. Tone Only, p < 0.01). **p < 0.01.
Figure 3
Figure 3
(A) Western blot analysis of left and right amygdala homogenates of Homecage controls, Tone only controls and animals that received Pavlovian fear conditioning with five tone-shock pairings 30, 60, or 90 min prior to sacrifice and brain extraction. (B) Western blot quantification of Arc expression in the left and right amygdala of the three groups described in (A). Fear conditioning produced a significant increase in Arc expression relative to the change produced by resting in the homecage or following tone presentation (FC 30 min vs. Tone Only, p < 0.01, FC 60 min vs. Tone Only, p < 0.01, FC 90 min vs. Tone Only, p < 0.01). Arc levels measured in the left and right amygdala did not differ in Homecage controls, Tone Only or the Fear Conditioning 30 min group. Arc expression was significantly elevated in the right amygdala compared to the left at 60 and 90 min following fear conditioning (FC 60 min: right vs. left, p < 0.05; FC 90 min: right vs. left, p < 0.05). *p < 0.05.
Figure 4
Figure 4
Mean (+SE) percentage of time spent freezing during training to each tone presentation. Animals utilized for immunohistochemistry underwent either five tone presentations or fear conditioning consisting of five tone-shock pairs. Animals that received a footshock coterminating with the tone presentation froze significantly more during Tones 2–5 (Tone 2: Fear Conditioning vs. Tone Only, p < 0.01; Tone 3: Fear Conditioning vs. Tone Only, p < 0.01; Tone 4: Fear Conditioning vs. Tone Only, p < 0.01; Tone 5: Fear Conditioning vs. Tone Only, p < 0.01). **p < 0.01.
Figure 5
Figure 5
(A) Immunohistochemical analysis of the effect of fear conditioning on Arc expression in the right and left basolateral amygdala. Fear conditioning elevates Arc immunoreactivity in the right, but not left basolateral amygdala. (B) Mean (+SE) number of Arc signals measured in the basolateral amygdala. Tone presentation alone did not alter Arc expression in the basolateral amygdala compared to the signals measured in Homecage controls. Fear conditioning with five tone-shock pairings produced a significant increase in Arc expression that was statistically greater in the right, relative to left basolateral amygdala (*p < 0.05). The level of Arc expression in the right amygdala of the Fear Conditioning group was also significantly greater than Arc expression measured in the right or left amygdala of homecage controls or the Tone only controls (*p < 0.05). (C) Quantification of Arc expression in the amygdala reveals that the percentage of cells expressing Arc was only elevated in the right basolateral amygdala of animals that experienced fear conditioning when compared to Homecage controls or Tone only controls (*p < 0.05).
Figure 6
Figure 6
(A) Mean (+SE) number of lever presses on the final day of initial training and in response to the unexpected change in reward magnitude on the Shift Day. On Day 10, animals accustomed to only (1) sucrose pellet following each FR-5 schedule (i.e., open circle and closed triangle), make significantly more lever presses than those given (10) sucrose pellets for each FR-5 during the first 10 days of training, (**p < 0.01). Animals assigned to either of the Nonshift groups (i.e., closed triangle and circle) did not alter lever pressing behavior on the Shift day. A decrease in reward quantity (i.e., Shift 10-1; open triangle) caused a significant increase in lever press responses relative to the number recorded on Day 10 (**p < 0.01) before the decrease in reward magnitude. Subjects in the Down-shift group displayed a significantly higher level of lever presses on the Shift day compared to animals that received (1) sucrose reward throughout the experiment (**p < 0.01; open triangle vs. closed triangle). Conversely, animals that experienced the Up-shift in reward from (1) to (10) sucrose pellets (i.e., open circle) decreased lever pressing behavior on the Shift day compared to Day 10 (**p < 0.01). (B) Mean (+SE) number of nose pokes into the food hopper on the last day of training and on the Shift day. On Day 10, the last day of training, animals that received (10) sucrose pellet following each FR 5, nose poked into the food hopper significantly more than animals that received (1) sucrose pellets (p < 0.05). Non-shift groups received the same reward magnitude throughout the experiment and did not altered nose poke behavior on Day 11. Animals that experienced an Up-shift in reward magnitude from (1) to (10) sucrose pellets increased nose poke behavior following the shift compared to Day 10 (p < 0.01). Additionally, these animals made more nose pokes on the Shift day compared to animals assigned to the Non-shift 10-10 group (p < 0.01). Conversely, animals that received a Down-shift from (10) to (1) sucrose pellets decreased nose poke behavior compared to Day 10 behavior (p < 0.05). *p < 0.05; **p < 0.01.
Figure 7
Figure 7
(A) Immunohistochemical analysis of Arc expression in the basolateral amygdala after an unexpected increase (Shift 1-10), decrease (Shift 10-1) or no change in reward magnitude following FR-5 lever pressing. The behavioral manipulations produced a significant change in left basolateral Arc expression only following an increase in reward quantity (Shift 1-10), whereas right basolateral Arc expression was elevated only by the unexpected reduction in reward quantity after the FR-5 (Shift 10-1). (B) Mean (+SE) number of Arc signals measured following the Shift in reward expectancies. There were no changes in Arc signal sampled from the amygdala of Non-shifted animals. Arc signals in the left basolateral amygdala were significantly greater than levels in the right (**p < 0.01) in subjects assigned to receive an up-shift in reward quantity (Shift 1-10). Conversely, Arc signals in the right basolateral amygdala were elevated compared levels sampled from left, in the group that experienced an unexpected Down-shift (Shift 10-1) in reward magnitude (**p < 0.01). (C) Quantification of the mean percentage of basolateral cells that express Arc following presentation of stimuli of opposing valence. Approximately 2.5% of cells in the basolateral amygdala express Arc in animals that received an expected reward quantity of either 10 or 1 sucrose pellets. Significantly more cells in the left, but not right basolateral amygdala expressed Arc following an expected Up-shift in reward quantity (**p < 0.01). Conversely, following a Down-shift more cells in the right basolateral amygdala expressed Arc compared to levels sampled in the left basolateral amygdala (**p < 0.01).

Similar articles

Cited by

References

    1. Ainge J. A., Keating G. L., Latimer M. P., Winn P. (2006). The pedunculopontine tegmental nucleus and responding for sucrose reward. Eur. J. Neurosci. 20, 1827–1837 10.1111/j.1460-9568.2004.03647.x - DOI - PubMed
    1. Amsel A., Roussel J. (1952). Motivational properties of frustration: I. Effect on a running response of the addition of frustration to the motivational complex. J. Exp. Psychol. 43, 363–368 10.1037/h0059393 - DOI - PubMed
    1. Baker B. B., Kim J. J. (2004). Amygdalar lateralization in fear conditioning: evidence for greater involvement of the right amygdala. Behav. Neurosci. 118, 15–23 10.1037/0735-7044.118.1.15 - DOI - PubMed
    1. Barot S. K., Chung A., Kim J. J., Bernstein I. L. (2009). Functional imaging of stimulus convergence in amygdalar neurons during Pavlovian fear conditioning. PLoS ONE 4:e6156 10.1371/journal.pone.0006156 - DOI - PMC - PubMed
    1. Blanchard D. C., Blanchard R. J. (1972). Innate and conditioned reactions to threat in rats with amygdaloid lesions. J. Comp. Physiol. Psychol. 81, 281–90 10.1037/h0033521 - DOI - PubMed

LinkOut - more resources