Behavioral and Neural Analysis of GABA in the Acquisition, Consolidation, Reconsolidation, and Extinction of Fear Memory

Abstract

The current review systematically documents the role of g-amino-butyric acid (GABA) in different aspects of fear memoryFacquisition and consolidation, reconsolidation, and extinction, and attempts to resolve apparent contradictions in the data in order to identify the function of GABA A receptors in fear memory. First, numerous studies have shown that pre-and post-training administration of drugs that facilitate GABAergic transmission disrupt the initial formation of fear memories, indicating a role for GABA A receptors, possibly within the amygdala and hippocampus, in the acquisition and consolidation of fear memories. Similarly, recent evidence indicates that these drugs are also detrimental to the restorage of fear memories after their reactivation. This suggests a role for GABA A receptors in the reconsolidation of fear memories, although the precise neural circuits are yet to be identified. Finally, research regarding the role of GABA in extinction has shown that GABAergic transmission is also disruptive to the formation of newly acquired extinction memories. We argue that contradictions to these patterns are the result of variations in (a) the location of drug infusion, (b) the dosage of the drug and/or (c) the time point of drug administration. The question of whether these GABA-induced memory deficits reflect deficits in retrieval is discussed. Overall, the evidence implies that the processes mediating memory stability consequent to initial fear learning, memory reactivation, and extinction training are dependent on a common mechanism of reduced GABAergic neurotransmission.

Effects of Repeated Stress on Age-Dependent GABAergic Regulation of the Lateral Nucleus of the Amygdala

“…Relatively less is known about the effects of stress on amygdala-dependent behaviors in adolescents; however, in several studies increased fear conditioning is accompanied by an impairment of fear extinction in adolescents and enhanced generalization of fear (Morrissey et al, 2011;Zhang and Rosenkranz, 2013;Muller et al, 2014;Padival et al, 2015). Both of these processes are sensitive to GABA within the BLA (Davis and Myers, 2002;Shaban et al, 2006;Lin et al, 2009;Sangha et al, 2009;Makkar et al, 2010;Lange et al, 2014). Similarly, impaired GABAergic systems may contribute to inappropriate affective responses characteristic of depression and anxiety.…”

Induction and Expression of Fear Sensitization Caused by Acute Traumatic Stress

“…During learning, sensory input relating to both the conditional stimulus (CS) and unconditional stimulus (US) converge on the BLA complex, a subregion of the amygdala, where a CS-US association is encoded via long-term potentiation at BLA synapses (Rogan et al, 1997;Kim and Jung, 2006). This plasticity is dependent upon excitatory N-methyl-D aspartate receptors (NMDAR) (Miserendino et al, 1990;Fanselow and Kim, 1994) and is modulated through inhibitory γ-aminobutyric acid (GABA)-ergic neurons (Ehrlich et al, 2009;Makkar et al, 2010). Under normal conditions, the BLA, consisting of lateral and basal nuclei, is critical for fear learning (Maren, 1998;Fanselow and LeDoux, 1999;Gale et al, 2004;McDannald and Galarce, 2011).…”

Aquaporin-4 Deficiency Impairs Synaptic Plasticity and Associative Fear Memory in the Lateral Amygdala: Involvement of Downregulation of Glutamate Transporter-1 Expression

“…Considering that the hearing of AQP4 KO mice is impaired (Li and Verkman, 2001), we used light but not tone as CS in fear conditioning test. In Pavlovian fear conditioning, memory acquisition refers to the process mediating the initial learning of the CS-US association during the training of fear conditioning, whereas memory consolidation refers to the process converting short-term memories into stable long-term memories (Abel and Lattal, 2001;Makkar et al, 2010). Cued fear memory encoded in the amygdala has been shown to be consolidated within 24 h and short-term fear memory is known to be maintained for up to 4 h (Schafe and LeDoux, 2000).…”