Pre-Training Reversible Inactivation of the Basal Amygdala (BA) Disrupts Contextual, but Not Auditory, Fear Conditioning, in Rats

Abstract

The basolateral amygdala complex (BLA), including the lateral (LA), basal (BA) and accessory basal (AB) nuclei, is involved in acquisition of contextual and auditory fear conditioning. The BA is one of the main targets for hippocampal information, a brain structure critical for contextual learning, which integrates several discrete stimuli into a single configural representation. Congruent with the hodology, selective neurotoxic damage to the BA results in impairments in contextual, but not auditory, fear conditioning, similarly to the behavioral impairments found after hippocampal damage. This study evaluated the effects of muscimol-induced reversible inactivation of the BA during a simultaneous contextual and auditory fear conditioning training on later fear responses to both the context and the tone, tested separately, without muscimol administration. As compared to control rats micro-infused with vehicle, subjects micro-infused with muscimol before training exhibited, during testing without muscimol, significant reduction of freezing responses to the conditioned context, but not to the conditioned tone. Therefore, reversible inactivation of the BA during training impaired contextual, but not auditory fear conditioning, thus confirming and extending similar behavioral observations following selective neurotoxic damage to the BA and, in addition, revealing that this effect is not related to the lack of a functional BA during testing.

Inhibition of Pyramidal Neurons in the Basal Amygdala Promotes Fear Learning

“…While studies have consistently illustrated the role of LA pyramidal neuron excitation in auditory fear conditioning, most of the published lesion and pharmacological inhibition studies have not supported a role for the BA in the acquisition of cue fear memories (Nader et al, 2001; Anglada-Figueroa and Quirk, 2005; Calandreau et al, 2005; Onishi and Xavier, 2010; Akagi Jordão et al, 2015). However, given that lesions and pharmacologic inhibitors lack neuronal specificity and can have broad and nonspecific effects on neural circuits, we revisited the role of the BA in auditory fear learning using a neuron-specific chemogenetic approach.…”

“…The BA receives glutamatergic input from the LA (Krettek and Price, 1978; Smith and Paré, 1994), as well as from the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC; Maren et al, 2013; Zelikowsky et al, 2014; Rozeske et al, 2015; McDonald and Mott, 2017). Although connections with the vHPC and mPFC are consistent with its role in contextual fear learning and in the expression of fear memories (Goosens and Maren, 2001; Calandreau et al, 2005; Amano et al, 2011; Akagi Jordão et al, 2015), the relevance of the BA to the acquisition of fear memories is less clear (Goosens and Maren, 2001; Nader et al, 2001; Anglada-Figueroa and Quirk, 2005). To address this issue, we used a neuron-specific chemogenetic approach to probe the relevance of BA pyramidal and GABA neurons to auditory fear conditioning.…”