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Prefrontal-insular gamma synchrony promotes modality-specific cognitive flexibility

Abstract

The ability to alter our behavior based on sensory inputs, such as odors or textures, is a necessity for adaptation. The medial prefrontal cortex (mPFC), important for cognitive function(Miller et al., 2001), produces gamma synchrony that is necessary for this behavioral flexibility tested in mice(Cho et al., 2015; Cho et al., 2020; Cho et al., 2023). It is unclear what contributes to this necessary gamma synchrony. The insula is also known to be necessary for proper cognitive function (Gehrlach et al., 2020; Menon et al., 2010; Kayyal et al., 2021), and also has bidirectional connectivity with the mPFC (Gehrlach et al., 2020). Here we apply optogenetic inhibition on the medial insular cortex (mIC) to mPFC projecting (mIC-mPFC) cell bodies and terminals during a Rule-Shifting task in mice to show that this projection is necessary for texture to odor cue rule shifts. We further determine the existence of gamma synchrony between mIC and mPFC parvalbumin interneurons (PVIs) during this task and find a difference in synchrony based on the cue type using a novel recording technique called transmembrane electrical measurements performed optically (TEMPO) (Marshall et al., 2016). This gamma synchrony was shown to be necessary for rule shifts to odor due to a deficit from out-of-phase optogenetic gamma stimulation. Overall, the results show the mIC is necessary for optimal rule shifting to an odor cue.