Generalization of fear learning is shaped by inhibitory sensory processing in mice

Abstract When an organism learns that a sensory stimulus predicts a threat, the brain’s neural representation of the stimulus somehow incorporates that information into early sensory processing. That altered sensory processing may causally shape the organism’s response to the stimulus. We used contextual fear conditioning in mice to induce odor avoidance that generalized across odors in proportion to their similarity to the conditioning odor. Visualization of odor representations in vivo revealed they were being reshaped by reductions in GABA B receptor-mediated inhibitory signaling in the presynaptic terminals of the olfactory nerve and downstream neurons in proportion to the generalized fear of each odor. Locally blocking GABA B receptors in the olfactory bulb caused mice to switch from generalizing fear in proportion to similarity to instead overgeneralizing fear to all odors equally. Learning-induced sensory plasticity thus plays a causal role in shaping fear generalization.