The Basolateral Amygdala: The Core of a Network for Threat Conditioning, Extinction, and Second-Order Threat Conditioning

Abstract

Threat conditioning, extinction, and second-order threat conditioning studied in animal models provide insight into the brain-based mechanisms of fear- and anxiety-related disorders and their treatment. Much attention has been paid to the role of the basolateral amygdala (BLA) in such processes, an overview of which is presented in this review. More recent evidence suggests that the BLA serves as the core of a greater network of structures in these forms of learning, including associative and sensory cortices. The BLA is importantly regulated by hippocampal and prefrontal inputs, as well as by the catecholaminergic neuromodulators, norepinephrine and dopamine, that may provide important prediction-error or learning signals for these forms of learning. The sensory cortices may be required for the long-term storage of threat memories. As such, future research may further investigate the potential of the sensory cortices for the long-term storage of extinction and second-order conditioning memories.

ParabrachialCalcaneurons mediate second-order conditioning

“…Higher-order conditioning, while not as extensively studied as first-order conditioning, likely plays a significant role in natural environments resembling the complexity of human memory formation 58 . It is well-documented that in first-order classical conditioning, the learning efficiency is maximized when the CS precedes the US 59,60 .…”

Correlational patterns of neuronal activation and epigenetic marks in the basolateral amygdala and piriform cortex following olfactory threat conditioning and extinction in rats

“…The threat conditioning and extinction paradigm in rodents has been a successful model for maladaptive fear learning and associated exposure therapy in humans. The basolateral amygdala (BLA) serves as a core component for contextual and cue-associated threat conditioning and extinction ( Fanselow and LeDoux, 1999 ; Bouton et al, 2021 ; Sepahvand et al, 2023b ). This structure interacts with the prefrontal cortex, hippocampus, sensory and neuromodulatory structures to form a larger network of threat circuitry ( Bouton et al, 2021 ; Sepahvand et al, 2023b ).…”

“…The basolateral amygdala (BLA) serves as a core component for contextual and cue-associated threat conditioning and extinction ( Fanselow and LeDoux, 1999 ; Bouton et al, 2021 ; Sepahvand et al, 2023b ). This structure interacts with the prefrontal cortex, hippocampus, sensory and neuromodulatory structures to form a larger network of threat circuitry ( Bouton et al, 2021 ; Sepahvand et al, 2023b ). As a central hub for threat memory encoding, the BLA converges sensory inputs with aversive stimuli to form long-term potentiation (LTP) at the sensory input synapses, leading to heightened output from the central amygdala defense pathways upon memory recall ( Sigurdsson et al, 2007 ; Pape and Pare, 2010 ; Johansen et al, 2011 ; Sepahvand et al, 2023b ).…”

“…This structure interacts with the prefrontal cortex, hippocampus, sensory and neuromodulatory structures to form a larger network of threat circuitry ( Bouton et al, 2021 ; Sepahvand et al, 2023b ). As a central hub for threat memory encoding, the BLA converges sensory inputs with aversive stimuli to form long-term potentiation (LTP) at the sensory input synapses, leading to heightened output from the central amygdala defense pathways upon memory recall ( Sigurdsson et al, 2007 ; Pape and Pare, 2010 ; Johansen et al, 2011 ; Sepahvand et al, 2023b ). Extinction is acquired through repeat exposure to a non-reinforced sensory conditioned stimulus following threat conditioning.…”

“…Extinction is acquired through repeat exposure to a non-reinforced sensory conditioned stimulus following threat conditioning. Extinction training engages either depotentiation of the synaptic LTP in the BLA, or new inhibitory learning processes to suppress the original threat memory ( Bouton et al, 2021 ; Sepahvand et al, 2023b ). The latter is achieved through a coordination of circuitry which includes inhibitory neurons of the amygdala, hippocampus and infralimbic prefrontal cortex ( Corcoran and Maren, 2001 ; Herry and Mons, 2004 ; Burgos-Robles et al, 2007 ; Mueller et al, 2008 ; Sotres-Bayon et al, 2009 ; Lacagnina et al, 2019 ).…”