The central nucleus of the amygdala is essential for acquiring and expressing conditional fear after overtraining

Abstract

The basolateral complex of the amygdala (BLA) is critical for the acquisition and expression of Pavlovian fear conditioning in rats. Nonetheless, rats with neurotoxic BLA lesions can acquire conditional fear after overtraining (75 trials). The capacity of rats with BLA lesions to acquire fear memory may be mediated by the central nucleus of the amygdala (CEA). To examine this issue, we examined the influence of neurotoxic CEA lesions or reversible inactivation of the CEA on the acquisition and expression of conditional freezing after overtraining in rats. Rats with pretraining CEA lesions (whether alone or in combination with BLA lesions) did not acquire conditional freezing to either the conditioning context or an auditory conditional stimulus after extensive overtraining. Similarly, post-training lesions of the CEA or BLA prevented the expression of overtrained fear. Lastly, muscimol infusions into the CEA prevented both the acquisition and the expression of overtrained fear, demonstrating that the effects of CEA lesions are not likely due to the destruction of en passant axons. These results suggest that the CEA is essential for conditional freezing after Pavlovian fear conditioning. Moreover, overtraining may engage a compensatory fear conditioning circuit involving the CEA in animals with damage to the BLA.Pavlovian fear conditioning is an important model for studying the neural mechanisms contributing to emotional learning and memory (Davis 1992;LeDoux 2000;Maren 2001Maren , 2005a. In this paradigm, a conditioned stimulus (CS), such as a tone, is presented with an aversive unconditional stimulus (US), such as a footshock. The pairing of the CS and the US comes to elicit conditioned fear responses (CRs), including increased heart rate, blood pressure, acoustic startle, and somatomotor immobility (i.e., freezing). It is now well established that the amygdala is critical for this form of learning (Fendt and Fanselow 1999 In contrast, the medial division of the CEA (CEm) has been posited to be the primary output structure of the amygdala. The CEA receives information from the LA via the intercalated nuclei, and it also receives direct projections from the BL and thalamus. The CEm, in turn, projects to brain areas involved in the production of the CR, including the periaqueductal gray and the lateral hypothalamus, which mediate freezing and cardiovascular response, respectively (LeDoux et al. 1988). However, recent studies suggest that the CEA may also have a role in the acquisition of conditional fear (Goosens and Maren 2003;Maren 2005a;Wilensky et al. 2006), and it is anatomically positioned to serve this role (Pare et al. 2004). These findings lend support to two competing models of information processing within the amygdala during learning. In the serial model, information about the CS and US enter and are associated within the BLA, and this information is then transmitted to the CEA for the expression of fear. Alternatively, the parallel model proposes that the BLA and CEA both perform associative function...

Activation of Group II Metabotropic Glutamate Receptors Inhibits the Discriminative Stimulus Effects of Alcohol via Selective Activity Within the Amygdala

“…Therefore, mGlu2/3 receptor activation may have interfered with the expression of the learned association in the amygdala, but not the nucleus accumbens. Indeed, the amygdala has been well characterized for its role in conditioned associations (Gallagher and Holland, 1994;LeDoux, 2003;Maren, 2005;Zimmerman et al, 2007), and mounting evidence suggests that this region has an important role in modulating associations between drugs of abuse and stimuli such as internal or environmental cues See et al, 2003;Theberge et al, 2010). It will be interesting for future experiments to examine the expression and function of mGlu2/3 receptors in the amygdala during different stages of discrimination learning (ie, acquisition vs maintenance) to determine whether learning the discrimination induces changes in mGlu2/3 receptors.…”

Inhibition of learning and memory by general anesthetics

“…[46][47][48][49][50][51] Unlike the hippocampus, the amygdala is necessary for the acquisition of fearful memories and their long-term storage and retrieval. 38,[52][53][54] In summary, explicit memory requires structures in the medial temporal lobe, such as the hippocampal formation and several cortical regions. Implicit memory involves a number of diverse brain regions, including the cerebellum, striatum, and midbrain.…”

Persistence of fear memory across time requires the basolateral amygdala complex

“…In addition, regardless of whether fear memories are 1 day or 1.5 years old, posttraining BLA lesions completely abolish the expression of fear (3). Collectively, such findings are consistent with a mnemonic role of the BLA in fear learning.However, recent studies have challenged this view and suggest that plasticity in other brain regions are capable of supporting fear conditioning (24,25). Indeed, there is growing evidence that fear conditioning can be established in the absence of the BLA.…”

“…However, recent studies have challenged this view and suggest that plasticity in other brain regions are capable of supporting fear conditioning (24,25). Indeed, there is growing evidence that fear conditioning can be established in the absence of the BLA.…”

“…Indeed, there is growing evidence that fear conditioning can be established in the absence of the BLA. In particular, deficits resulting from either lesions or inactivations of the BLA can be overcome with extensive overtraining (7,(25)(26)(27). Furthermore, both Zimmerman et al (25) and Wilensky et al (24) have recently shown that disruption of central nucleus of the amygdala (CEA) function can prevent fear conditioning.…”