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

Abstract

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.