ACC-projecting claustral neurons are required during cue pre-exposure for latent inhibition

In a noisy world, learning to ignore stimuli that repeatedly occur without consequence is essential for adaptive behavior. Latent inhibition, in which prior inconsequential cue exposure slows subsequent associative learning, captures this capacity. The claustrum is densely interconnected with frontal cortex and implicated in cortical modulation and attentional control, yet whether it contributes to the pre-exposure-dependent processes that support latent inhibition remains unclear.

Here we show, using projection-defined chemogenetic inhibition in rats, that claustral neurons projecting to anterior cingulate cortex, a prefrontal region implicated in attention and strongly interconnected with the claustrum, are required during cue pre-exposure for latent inhibition. Inhibition during cue pre-exposure abolishes latent inhibition, whereas the chemogenetic drug alone does not disrupt latent inhibition in control rats. Inhibition during conditioning leaves cue–reward acquisition intact and spares learning in an odor-guided go/no-go task.

Thus, activity in claustral neurons projecting to anterior cingulate cortex during nonreinforced exposure is necessary for the subsequent expression of latent inhibition, without broadly disrupting reinforcement learning or response control. Together, these results provide projection-defined causal evidence that claustral neurons projecting to anterior cingulate cortex contribute to pre-exposure-dependent modulation of later cue learning. We thank the Laboratory Animal Resource Center and the Optical Imaging Facility at the Chinese Institute for Brain Research, Beijing, for their support.

This work was supported by the Brain Science and Brain-like Intelligence Technology—National Science and Technology Major Project (2022ZD0207500) and the Chinese Institute for Brain Research, Beijing. State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University & Chinese Institute for Brain Research, Beijing, China IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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