In traditional Pavlovian fear conditioning paradigms, animals associate a neutral sensory cue, such as a sound or light, with an aversive stimulus like a mild electric shock. Over time, they develop a conditioned fear response to the cue alone. However, in the real world, cues that predict danger usually lack temporal predictability. Environmental unpredictability is known to enhance aversive memory. The basolateral amygdala (BLA) plays a critical role in forming aversive memories, mediating the convergence of multimodal sensory information. Previous research on the BLA has shown that different neuronal populations within this area encode valence-associative memories during fear conditioning. Our study aims to explore neuronal network activity within the BLA between predictable versus unpredictable fear conditioning. We employed time-lapse microendoscopic recording techniques to observe BLA neurons' somal calcium activity during fear conditioning and an auditory fear recall test (Chapter 3). We identified neurons with different patterns during these paradigms. 'Memory Winners' showed successful convergence of sensory information consistent with retention of the fear memory, while 'Memory Losers' failed to display conditioned stimulus (CS)-evoked calcium responses during fear recall, indicating a loss of fear memory. A further group, the 'Fear Expression' neurons lacked learning-related plasticity for the tone and shock but showed early CS-evoked activity during fear recall.
When we introduced unpredictability during fear conditioning, we observed that the distinct functional classes of neurons remained consistent across paradigms. However, the tone and footshock evoked activity did differ within these neuronal classifications. 'Memory Winners' showed early tone- and shock-evoked increased responsivity, while 'Memory Losers' displayed varying shock responsivity depending on whether the conditioning was predictable or unpredictable. Additionally, we identified an extinction-related functional sub-classification of neurons within the BLA. These included neurons that became less responsive during late extinction trials ('extinction-sensitive'), neurons that showed increased CS-evoked activity during late extinction ('extinction learning'), and neurons that maintained consistent activity levels during fear recall and late extinction trials ('fear sustained'). In a departure from most studies that focus on unexpected stimuli or outcomes, we also investigated whether attention signals, defined by transient changes in BLA neuronal calcium activity, are generated when expected stimuli are omitted (Chapter 4). Using neuronal calcium imaging in the BLA, we found that many amygdala neurons displayed attention signals in a stochastic manner during omitted punishment. These neurons showed enhanced sensory processing and plasticity compared to neurons without error signals. Finally, in Chapter 5, we found that unpredictable fear conditioning affected fear-related freezing behaviors and increased the cFos expression in both the BLA and the lateral septum (LS). This supports the notion that the amygdala is strategically positioned to perceive unpredictable aversive cues during conditioning. Collectively, our findings suggest that unpredictability of aversive cues results in specific alterations in the BLA and other brain areas. / 2025-01-24T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/47957 |
| Date | 24 January 2024 |
| Creators | Burgess, JoColl Alexis |
| Contributors | Rockland, Kathleen |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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