Insula to mPFC reciprocal connectivity differentially underlies novel taste neophobic response and learning in mice

Abstract

To survive in an ever-changing environment, animals must detect and learn salient information. The anterior insular cortex (aIC) and medial prefrontal cortex (mPFC) are heavily implicated in salience and novelty processing, and specifically, the processing of taste sensory information. Here, we examined the role of aIC-mPFC reciprocal connectivity in novel taste neophobia and memory formation, in mice. Using pERK and neuronal intrinsic properties as markers for neuronal activation, and retrograde AAV (rAAV) constructs for connectivity, we demonstrate a correlation between aIC-mPFC activity and novel taste experience. Furthermore, by expressing inhibitory chemogenetic receptors in these projections, we show that aIC-to-mPFC activity is necessary for both taste neophobia and its attenuation. However, activity within mPFC-to-aIC projections is essential only for the neophobic reaction but not for the learning process. These results provide an insight into the cortical circuitry needed to detect, react to- and learn salient stimuli, a process critically involved in psychiatric disorders.

Brain-wide screen of prelimbic cortex inputs reveals a functional shift during early fear memory consolidation

“…The INS as a whole has classically been involved in taste learning (Yiannakas & Rosenblum, 2017) and the encoding of conditioned taste aversion (Sano et al, 2014), but has also been been implicated in recent CFC recall (Alves et al, 2013) as well as in auditory fear memory extinction (Klein et al, 2021). The INS to mPFC reciprocal connectivity has only been investigated in the context of taste learning, where it was recently found necessary for the expression of novel taste aversion (Kayyal et al, 2021). However, a direct role of INS input to PL during fear memory consolidation has not been described before.…”

Optogenetic stimulation of anterior insular cortex neurons reveals causal mechanisms underlying suppression of the default mode network by the salience network

“…We suggest that information flow between AI and RSC may rely on one or more intermediary nodes in the mPFC. Indeed, rodent tract-tracing studies reveal that the AI is connected to Cg and PrL (17, 19, 63, 67), which in turn are connected to the RSC via the cingulum bundle (63). The PrL is also directly connected to Cg, and given that RSC has relatively dense connectivity with Cg compared to other prefrontal regions, a multi-node pathway for information flow from AI→PrL→Cg→RSC is also plausible.…”

The impact of familiarity on cortical taste coding

“…Furthermore, the effect was not likely due to cells merely dropping out of the imaging field of view with time, as active cell number remained stable across an identical number of pre-taste days in which mice only drank water. Prior immunocytochemical studies reported reduced numbers of activated neurons (i.e., c-Fos or pERK expression) in animals consuming familiar tastes versus novel tastes (Lin et al, 2012;Bamji-Stocke et al, 2018;Kayyal et al, 2021). In each of these studies, the familiar condition was achieved by allowing animals 6 or more days of exposure prior to perfusion.…”

“…Relatively few studies have explored the neural correlates of taste familiarization, and those have reported somewhat conflicting results. Expression of neuronal activity markers such as the immediate early gene c-Fos, or pERK (phosphorylated extracellular regulated kinase), is increased in GC and other taste-related forebrain areas following exposure to novel taste stimuli and subsequently decreases with repeated experience (Koh et al, 2003; Lin et al, 2012; Bamji-Stocke et al, 2018; Kayyal et al, 2021). In contrast, a study of multiunit activity in the GC in rats actively sampling a taste stimulus over several days found that the average response to the stimulus actually increased as the taste became familiar, although this change was only apparent in the late phase of the response (Bahar et al, 2004).…”