Sidman Instrumental Avoidance Initially Depends on Lateral and Basal Amygdala and Is Constrained by Central Amygdala-Mediated Pavlovian Processes

Abstract

Background The lateral (LA) and central (CE), but not basal (B), amygdala nuclei are necessary for reactive Pavlovian fear responses such as freezing. The amygdala also plays a key role in the acquisition and expression of active instrumental defensive behaviors, but little is known about the specific roles of amygdala nuclei. Using a Sidman active avoidance (AA) task, we examined the necessity of LA, B, and CE for learning and performance. Pavlovian freezing was simultaneously assessed to examine the contributions of amygdala nuclei to the transition from reactive to active defensive responding. Methods Rats received electrolytic lesions of LA, CE or B before AA training, or following overtraining. Rats that expressed low levels of AA performance during training received bilateral electrolytic lesions to CE to eliminate competing freezing reactions and rescue AA. AA performance and freezing were assessed. Results Damage to LA and B, but not CE, impaired the acquisition of AA. Performance of AA became amygdala-independent following overtraining. CE lesions abolished Pavlovian freezing and rescued instrumental AA performance in rats that expressed low levels of avoidance responses and high levels of freezing during training. Conclusions While the acquisition of Pavlovian fear depends on LA and CE, but not B, acquisition of instrumental AA is dependent on LA and B, but not CE. CE-dependent Pavlovian processes that control freezing can constrain avoidance behavior. Performance of well-trained AA becomes independent of all three amygdala nuclei. Thus, it appears that different output pathways of LA mediate reactive and active conditioned defensive responding.

Bimodal Control of Fear-Coping Strategies by CB1Cannabinoid Receptors

“…Third, both freezing and active behaviors reached higher levels during tone presentation than during the pre-tone period in all animals, indicating that they were tone-induced (i.e., fear-elicited) behavioral responses. Finally, as previously reported in rats (Lázaro-Muñoz et al, 2010;Vicens-Costa et al, 2011), we were able to measure the relationship between the type of coping adopted by individual mice in fear conditioning and active avoidance performances. Altogether, these observations indicate that passive or active fear coping strategies likely represent individual behavioral traits maintained over different experimental conditions.…”

“…tioning were those performing the poorer in active avoidance learning (Lázaro-Muñoz et al, 2010;Vicens-Costa et al, 2011). Previously fear-conditioned mice were submitted to one active avoidance session.…”

“…The ability to efficiently cope with potential dangers strongly influences the consequences of aversive stimuli on the organisms (Hartley and Phelps, 2010). Human and animal studies revealed individual differences in the way of mastering imminent environmental challenges (Blanchard et al, 2001;Lázaro-Muñoz et al, 2010;Schlund et al, 2010). In rodents, defensive behaviors were clustered in either passive (or reactive) coping or active (or proactive) coping, respectively (Koolhaas et al, 1999).…”

“…The amygdaloid complex is a major integration site for learning and adaptation of passive and active responses to fear conditioned stimuli (LeDoux, 2000;Myers and Davis, 2007;Choi et al, 2010;Hartley and Phelps, 2010;Lázaro-Muñoz et al, 2010), and amygdalar CB 1 receptors are necessary for a normal expression of conditioned freezing (Marsicano et al, 2002;Tan et al, 2010Tan et al, , 2011Kamprath et al, 2011). The virus-mediated re-expression of CB 1 receptors in CB 1 Ϫ/Ϫ mice shows that amygdalar CB 1 receptor signaling is sufficient to mediate adaptation of conditioned freezing and, importantly, to restore a normal switch between passive and active coping.…”

Amygdala Subregions Tied to SSRI and Placebo Response in Patients with Social Anxiety Disorder

“…Animal studies have reported differential distributions of the serotonin transporter protein (Rourke and Fudge, 2006) as well as serotonin-1A and other receptors (Pazos et al, 1987) across these subnuclei, which may underlie variation in treatment effects on amygdala firing. Damaging neurons of the central, basal, and lateral nuclei yields different mediation of fear-related behaviors in animals (Lázaro-Muñoz et al, 2010). Pharmacological studies have shown that the BLA and central amygdala, in particular, have distinct roles in the anxiolytic effect of benzodiazepines (Green and Vale, 1992).…”