Role of amygdala and hippocampus in the neural circuit subserving conditioned defeat in Syrian hamsters

Abstract

We examined the roles of the amygdala and hippocampus in the formation of emotionally relevant memories using an ethological model of conditioned fear termed conditioned defeat (CD). Temporary inactivation of the ventral, but not dorsal hippocampus (VH, DH, respectively) using muscimol disrupted the acquisition of CD, whereas pretraining VH infusions of anisomycin, a protein synthesis inhibitor, failed to block CD. To test for a functional connection between the VH and basolateral amygdala (BLA), we used a classic functional connectivity design wherein injections are made unilaterally in brain areas either on the same or opposite sides of the brain. A functional connection between the BLA and VH necessary for the acquisition of CD could not be found because unilateral inactivation of either BLA alone (but not either VH alone) was sufficient to disrupt CD. This finding suggested instead that there may be a critical functional connection between the left and right BLA. In our final experiment, we infused muscimol unilaterally in the BLA and assessed Fos immunoreactivity on the contralateral side following exposure to social defeat. Inactivation of either BLA significantly reduced defeat-induced Fos immunoreactivity in the contralateral BLA. These experiments demonstrate for the first time that whereas the VH is necessary for the acquisition of CD, it does not appear to mediate the plastic changes underlying CD. There also appears to be a critical interaction between the two BLAs such that bilateral activation of this brain area must occur in order to support fear learning in this model, a finding that is unprecedented to date.

Figure 1.

Histological recreation of injection sites of animals receiving infusions of muscimol into the (A) DH and (B) VH. (Dots) The site of injection in one or more animals; (squares) misplaced injection sites. (Drawings are adapted from Morin and Wood [2001] and reprinted here with permission from Elsevier ©2001.)

Figure 2.

Histological recreation of injection sites of animals receiving infusion of muscimol into the (A) BLA and (B) VH. (Dots) The site of injection in one or more animals; (squares) misplaced injection sites. (Drawings are adapted from Morin and Wood [2001] and reprinted here with permission from Elsevier ©2001.)

Figure 3.

Total duration (mean ± SEM) of submissive, aggressive, social, and nonsocial behavior displayed by defeated hamsters during a 5-min test with a nonaggressive intruder. Animals received bilateral infusions of muscimol in the DH immediately before being defeated for 15 min. There was no effect of drug on any behavior class.

Figure 4.

Total duration (mean ± SEM) of submissive, aggressive, social, and nonsocial behavior displayed by defeated hamsters during a 5-min test with a nonaggressive intruder. Animals received bilateral infusions of muscimol in the VH immediately before being defeated for 15 min. Significant differences are indicated by unshared letters (P < 0.05).

Figure 5.

Total duration (mean ± SEM) of submissive, aggressive, social, and nonsocial behavior displayed by defeated hamsters during a 5-min test with a nonaggressive intruder. Animals received bilateral infusions of anisomycin in the VH immediately before being defeated for 15 min. There was no effect of drug on any behavior class.

Figure 6.

Total duration (mean ± SEM) of submissive, aggressive, social, and nonsocial behavior displayed by defeated hamsters during a 5-min test with a nonaggressive intruder. Animals received infusions of muscimol in the VH and/or BLA immediately before being defeated for 15 min. Significant differences are indicated by unshared letters (P < 0.05).

Figure 7.

Photomicrographs of Fos-immunoreactive cells (dark dots) in the basolateral amygdala (BLA) and surrounding areas in the (A) saline/defeat, (B) muscimol/defeat, and (C) muscimol/no defeat groups.