Memory trace reactivation and behavioral response during retrieval are differentially modulated by amygdalar glutamate receptors activity: interaction between amygdala and insular cortex

Abstract

The insular cortex (IC) is required for conditioned taste aversion (CTA) retrieval. However, it remains unknown which cortical neurotransmitters levels are modified upon CTA retrieval. Using in vivo microdialysis, we observed that there were clear elevations in extracellular glutamate, norepinephrine, and dopamine in and around the center of the gustatory zone of the IC during CTA retrieval. Additionally, it has been reported that the amygdala-IC interaction is highly involved in CTA memory establishment. Therefore, we evaluated the effects of infusions of an AMPA receptor antagonist (CNQX) and a NMDA receptor antagonist (APV) into the amygdala on CTA retrieval and IC neurotransmitter levels. Infusion of APV into the amygdala impaired glutamate augmentation within the IC, whereas dopamine and norepinephrine levels augmentation persisted and a reliable CTA expression was observed. Conversely, CNQX infusion into the amygdala impaired the aversion response, as well as norepinephrine and dopamine augmentations in the IC. Interestingly, CNQX infusion did not affect glutamate elevation in the IC. To evaluate the functional meaning of neurotransmitters elevations within the IC on CTA response, we infused specific antagonists for the AMPA, NMDA, D1, and β-adrenergic receptor before retrieval. Results showed that activation of AMPA, D1, and β-adrenergic receptors is necessary for CTA expression, whereas NMDA receptors are not involved in the aversion response.

Activity of Insula to Basolateral Amygdala Projecting Neurons is Necessary and Sufficient for Taste Valence Representation

“…Presentation of the CS for CTA induces marked ERK activation in both the IC and BLA (Berman, 2003;Lin et al, 2010) and activation of BLA projections to reward centers (Inui et al, 2013). However, electrophysiological activity is inhibited in the majority of recorded BLA units in vivo (Uwano et al, 1995;Kim et al, 2010), Nonetheless, electrophysiological and molecular changes within excitatory BLA neurons have indeed been reported in a number of studies examining CTA acquisition and retrieval (Yasoshima and Yamamoto, 2005;Barot et al, 2008;Guzman-Ramos and Bermudez-Rattoni, 2012;Osorio-Gó mez et al, 2017). Perhaps, despite their activation during acquisition, only a small proportion of BLA neurons is reactivated during retrieval, while the contribution of fibers projecting through or away from the BLA is indeed significant (Dunn and Everitt, 1988;Bahar et al, 2004;Inui et al, 2019).…”

The Insula and Taste Learning

“…Furthermore, unlike blockade of the NMDAR-CaMKIIα effects, CNQX (competitive AMPA/kainate receptor antagonist) microinfusion into the IC 1 h following novel taste learning suppresses CTA retrieval even when the US is delivered 4 h later (Adaikkan and Rosenblum, 2015 ). On the other hand, microinfusion of CNQX into the amygdala disrupts CTA expression and suppresses norepinephrine and dopamine augmentations in the IC (Osorio-Gomez et al, 2016 ). Novel taste learning itself induces up-regulation of the GluR1 AMPAR subunit, while AMPAR trafficking and signaling in the IC influences the ability of long-term memory trace inputs to form negative CS-US associations (Adaikkan and Rosenblum, 2015 ; Osorio-Gomez et al, 2016 ).…”

“…On the other hand, microinfusion of CNQX into the amygdala disrupts CTA expression and suppresses norepinephrine and dopamine augmentations in the IC (Osorio-Gomez et al, 2016 ). Novel taste learning itself induces up-regulation of the GluR1 AMPAR subunit, while AMPAR trafficking and signaling in the IC influences the ability of long-term memory trace inputs to form negative CS-US associations (Adaikkan and Rosenblum, 2015 ; Osorio-Gomez et al, 2016 ). AMPAR-dependent activity in the IC might underlie the ability of the brain to encode the aversion expected by a sensory experience and to re-evaluate its relevant weight in predicting the US in relation to inputs arising from the extended taste learning circuit upon subsequent consolidation trials (Eisenberg et al, 2003 ).…”

Transcriptomic Characterization of the Human Insular Cortex and Claustrum

“…Studies have indicated its role in working memory of taste (Ragozzino and Kesner, 1999), conditioned taste aversion (Schier et al, 2016) and taste learning [see review by Yiannakas and Rosenblum (2017)]. This is in part mediated by glutamatergic and dopaminergic transmission (Guzmán-Ramos et al, 2010; Osorio-Gómez et al, 2017), which also showed enrichment in the insula. However, no gene ontology groups corresponding to taste specifically were enriched in the IC.…”