Yiannakas, A. | bioRxiv Science

bioRxiv2021

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

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.

neuroscience↗

bioRxiv2021

Parvalbumin Interneurons Inhibition onto BLA Projecting Neurons of the Anterior Insula Orchestrates Aversive Taste Memory Retrieval

Memory retrieval refers to the fundamental ability of organisms to make use of acquired, sometimes inconsistent, information about the world. While memory acquisition has been studied extensively, the neurobiological mechanisms underlying memory retrieval remain largely unknown. The anterior insula (aIC) is indispensable in the ability of mammals to retrieve associative information regarding tastants that have been previously linked with gastric malaise. Here, we show that aversive taste memory retrieval promotes cell-type-specific activation in the aIC. Aversive, but not appetitive taste memory retrieval, relies on specific changes in activity and connectivity at parvalbumin (PV) inhibitory synapses onto aIC pyramidal neurons projecting to the basolateral amygdala. PV aIC interneurons, coordinate aversive taste memory retrieval, and are necessary for its dominance when conflicting internal representations are encountered. This newly described interaction of PV and a subset of excitatory neurons can explain the coherency of aversive memory retrieval, an evolutionary pre-requisite for animal survival. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=188 SRC="FIGDIR/small/433377v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1e73ba2org.highwire.dtl.DTLVardef@1fc234dorg.highwire.dtl.DTLVardef@719d74org.highwire.dtl.DTLVardef@1184bb9_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LIRetrieval of Conditioned Taste Aversion (CTA) memories at the anterior insular cortex activates Parvalbumin (PV) interneurons and increases synaptic inhibition onto activated pyramidal neurons projecting to the basolateral amygdala (aIC-BLA). C_LIO_LIUnlike innately appetitive taste memory retrieval, CTA retrieval increases the amplitude and frequency of synaptic inhibition onto aIC-BLA projecting neurons, that is dependent on activity in aIC PV interneurons. C_LIO_LIActivation of aIC PV interneurons is necessary for the expression of learned taste avoidance, in both sexes, regardless of stimulus identity. C_LIO_LIExtinction of aversive taste memories suppresses the frequency, but not the amplitude of synaptic inhibition on aIC-BLA projecting neurons. C_LIO_LIThe reinstatement of aversive taste memories following extinction is dependent upon activation of aIC PV interneurons and increases in the frequency of inhibition on aIC-BLA projecting neurons. C_LI

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