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April 21st, 2025
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University of Pennsylvania
neuroscience
biorxiv

The role of inhibitory neurons in novelty sound detection in regular and random statistical contexts.

Ding, X.Open in Google Scholar•Vogler, N. W.Open in Google Scholar•Tobin, M.Open in Google Scholar•Garami, L.Open in Google Scholar•Wood, K. C.Open in Google Scholar•Geffen, M. N.Open in Google Scholar

Detecting statistical regularities in sound and responding to violations of these patterns, termed novelty detection, is a core function of the auditory system. Human studies have shown that novelty responses are enhanced in regular compared to random auditory contexts, but the underlying circuit mechanisms remain unclear. Here, we examined how inhibitory neurons contribute to context-dependent novelty responses in mouse auditory cortex. Using two-photon calcium imaging in the auditory cortex of awake head-fixed male and female mice, we recorded neuronal activity during presentation of spectro-temporally rich ripple sounds, with novel ripples embedded in either regular or random ripple sequences. AC neurons exhibited enhanced responses to novel sounds in regular contexts compared to random ones. To identify circuit mechanisms, we selectively inactivated parvalbumin (PV), somatostatin (SST), or vasoactive intestinal polypeptide (VIP) inhibitory neurons using optogenetics during imaging. Inactivation of PV and SST neurons broadly increased novelty responses in both contexts. In contrast, VIP inactivation selectively reduced responses to novel stimuli in the regular context, abolishing the context-dependent enhancement. At the population level, inactivating all three neuronal subtypes increased detectability of the novel stimulus, but with VIP inactivation, the shift was stronger for regular than random context. These findings reveal a distinct role for VIP neurons in modulating prediction error signals based on temporal structure, suggesting that VIP circuits are critical for context-sensitive auditory processing.

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