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September 26, 2025PLoS Biology3 citationsOpen Access

Extinction and subsequent updating of innate fear responses to a visual looming stimulus rely on hippocampus-dependent mechanisms

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PCPaul ConwayLALivia AutoreAZAndrea Zamora

Key Points

  • Attenuation of innate fear responses occurs with repeated exposure to looming stimuli, enhancing adaptability.
  • Fiber photometry shows attenuated responses in the SC and PAG, which do not recover when behavior does.
  • c-Fos expression analysis identifies a ventral CA1 ensemble active during both innate and learned fear responses.
  • Ventral CA1 is crucial for learned fear responses but not necessary for innate defensive behavior.

Abstract

Animals rely on innate and learned behavior to respond to their environment, but how the brain balances hardwired responses with adaptive flexibility remains unclear. Here, we demonstrate that innate looming stimulus responses in Mus musculus can be attenuated via repeated unreinforced presentation. This attenuation is long-lasting and generalizing, but is rapidly recovered when the stimulus is paired with an electric foot-shock. Fiber photometry recordings reveal attenuation of responses to visual looming stimuli in the SC and PAG, which do not recover following recovery of behavioral responses. Analysis of c-Fos expression uncovered a ventral CA1 (vCA1) ensemble that is active during both innate and learned looming fear responses. We report that this vCA1 engram is not necessary for innate defensive behavior but is necessary for learned fear responses. These findings reveal a novel role of the hippocampus in adapting to looming stimuli, and provide a platform for understanding the interaction of memory and instinct.

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Cite This Study

Conway et al. (2025) studied this question.

synapsesocial.com/papers/68d6c671b1249cec298b2198https://doi.org/10.1371/journal.pbio.3003391
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