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

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.How does the brain balance innate responses with adaptive learning when reacting to threats? This study shows that repeated exposure to looming stimuli reduces innate defensive responses via hippocampal modulation, revealing a ventral CA1 engram essential for learned—but not innate—fear, and highlighting the hippocampus’ role in instinct adaptation.