Threat Memory in the Sensory Cortex: Insights from Olfaction

Abstract

The amygdala has long held the center seat in the neural basis of threat conditioning. However, a rapidly growing literature has elucidated extra-amygdala circuits in this process, highlighting the sensory cortex for its critical role in the mnemonic aspect of the process. While this literature is largely focused on the auditory system, substantial human and rodent findings on the olfactory system have emerged. The unique nature of the olfactory neuroanatomy and its intimate association with emotion compels a review of this recent literature to illuminate its special contribution to threat memory. Here, integrating recent evidence in humans and animal models, we posit that the olfactory (piriform) cortex is a primary and necessary component of the distributed threat memory network, supporting mnemonic ensemble coding of acquired threat. We further highlight the basic circuit architecture of the piriform cortex characterized by distributed, auto-associative connections, which is prime for highly efficient content-addressable memory computing to support threat memory. Given the primordial role of the piriform cortex in cortical evolution and its simple, well-defined circuits, we propose that olfaction can be a model system for understanding (transmodal) sensory cortical mechanisms underlying threat memory.

Auditory Aversive Generalization Learning Prompts Threat-Specific Changes in Alpha-Band Activity

“…Consistent with findings using fMRI (Yin et al, 2020) and event-related potentials (Thigpen, 2017), the present trial-by-trial analyses suggest that initial discrimination between threat and safety cues involves higher-order cortices involved in parietal alpha power changes. The observation that the discrimination between threat and safety cues is attenuated rather than increased later in the acquisition phase supports the notion that sustained aversive conditioning prompts discrimination at increasingly lower levels of the cortical hierarchy, eventually leading to threat representations in sensory areas (Li & Wilson, 2023).…”

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

“…The cross-talk demonstrated between epigenetic marks makes them reciprocally regulating ( Gupta et al, 2010 ; Parrish et al, 2010 ; Ell et al, 2023 ) which is a complexity that potentially occurs during any type of learning. The strong correlation seen between epigenetic marks in the BLA and pPC in adult rats during associative learning and extinction, and their correlations with neuronal activity indexed by cFos, support the view that both BLA and PC are critical memory encoding and storage structures ( Li and Wilson, 2023 ). A larger interaction, which includes the correlated epigenetic changes between the aPC and BLA of aged brains, may implicate a shift to a less specific epigenetic dynamic emerging with aging.…”

“…One novel finding in this study is that BLA and pPC neuronal activities indexed by cFos, are highly synchronized in odor threat conditioning and extinction learning. Similar to hippocampus-dependent memory that undergoes substantial system consolidation, which engages cortical areas for remote memory storage ( Frankland and Bontempi, 2005 ), recent evidence has portrayed BLA as the initial encoding structure for emotional learning, while sensory cortices serve as long-term storage of emotional memory ( Sacco and Sacchetti, 2010 ; Cambiaghi et al, 2016a ; Mouly et al, 2022 ; You et al, 2022 ; Li and Wilson, 2023 ). This theory is supported anatomically by the existence of strong mutual connections between the pPC and BLA ( Majak et al, 2004 ).…”

Sensing fear: fast and precise threat evaluation in human sensory cortex

“…Together, extant findings suggest that threat conditioning generates lasting memory traces in the sensory cortex. Importantly, the sensory cortex likely serves as a key site of long-term repository of mnemonic threat codes [13,14], underpinning stable, enduring AAR of threat (also see [79] for a review of threat engrams in the sensory cortex). Consequently, as sensory information about a threat cue reaches the sensory cortex in the initial afferent volley, it will activate these mnemonic codes/AAR (aka, "threat schemata" [36,80]), eliciting fast and precise threat evaluation.…”