Parvalbumin interneuron inhibition onto anterior insula neurons projecting to the basolateral amygdala drives aversive taste memory retrieval

Intrinsic excitability in layer IV-VI anterior insula to basolateral amygdala projection neurons encodes the confidence of taste valence

“…Guided by evidence regarding the induction of plasticity cascades, the expression of immediate early genes, as well as the timeframes involved in LTP and LTD at the IC (Rosenblum et al, 1997;Hanamori et al, 1998;Jones et al, 1999;Escobar and Bermúdez-Rattoni, 2000), the five treatment groups were sacrificed 1 hour following taste consumption. Even though changes in activity can be observed within seconds to minutes, depending on their novelty, salience and valence (Barot et al, 2008;Lavi et al, 2018;Wu et al, 2020), sensory experiences can modulate the function of IC neurons for hours (Juárez-Muñoz et al, 2017;Rodríguez-Durán et al, 2017;Haley et al, 2020;Yiannakas et al, 2021).We had previously identified a CaMKII-dependent short-term memory trace at the IC that last for the first 3 hours following taste experiences, regardless of their valence (Adaikkan and Rosenblum, 2015). To address whether similar time-dependency of the physiological correlations engaged by the IC during novel taste learning, a 6 th group was sacrificed 4 hours following novel saccharin exposure (Figure 1 -Saccharin 1x (4hrs)).…”

“…At the IC, the maturation of GABAergic PV circuits is key for multisensory integration and pruning of cross-modal input to coordinate the detection of relevant information (Gogolla et al, 2014). Activation of IC PV disrupts the expression of taste-guided goal-directed behavior (Vincis et al, 2020), and enhances taste-guided aversive responses (Yiannakas et al, 2021). Our findings could be indicative of a prediction-dependent decoupling mechanism at the IC, whereby the restriction of bursting activity in LIV-VI aIC-BLA neurons impinges on innate drives towards the tastant and further learning, depending on prior experience.…”

“…Electrophysiological studies of the influence of learned aversive taste memory retrieval on aIC-BLA excitability WT mice were treated with viral constructs labelling aIC-BLA projecting neurons to assess the electrophysiological properties of the projection during aversive or appetitive taste memory retrieval. Upon recovery, mice in CTA retrieval group were trained in CTA for saccharin (LiCl 0.14M, 1.5% body weight), while the appetitive saccharin retrieval group (Saccharin 2x) received a matching body weight adjusted injection of saline (Yiannakas et al, 2021). Three days following conditioning, both groups underwent a memory retrieval task, receiving 1.0mL of the conditioned tastant 1 hour prior to sacrifice (Figures 2, 4).…”

“…Electrophysiological studies of the influence of learned aversive taste memory extinction and reinstatement on aIC-BLA excitability Electrophysiological studies of CTA extinction and reinstatement were conducted in a cohort of WT male mice (Yiannakas et al, 2021). Following surgery, recovery and water restriction, animals were randomly assigned to the extinction and reinstatement groups (Figures 3-4).…”

The Engram’s Dark Horse: How Interneurons Regulate State-Dependent Memory Processing and Plasticity

“…CFM consolidation relies on activity of D1/5 dopamine receptors, and downstream activation of cAMP and ERK, in hippocampal PV+ interneurons in the hours following CFC (Karunakaran et al, 2016). PV+ interneurons in various brain structures, including the insular cortex, medial septum, and nucleus accumbens also play critical roles during memory recallcoordinating activity within limbic structures during recall of appetitive and aversive associations (Trouche et al, 2019;Sans-Dublanc et al, 2020;Yiannakas et al, 2021). Altogether, these data highlight the importance of PV+ interneurons for memory processing, and underscore that the connectivity between PV+ interneurons and the principal cells they target is crucial for engram formation.…”