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

Abstract

Conditioned taste aversion (CTA) is an associative learning paradigm, wherein consumption of an appetitive tastant (e.g., saccharin) is paired to the administration of a malaise-inducing agent, such as intraperitoneal injection of LiCl. Aversive taste learning and retrieval require neuronal activity within the anterior insula (aIC) and the basolateral amygdala (BLA). Here, we labeled neurons of the aIC projecting to the BLA in adult male mice using a retro-AAV construct and assessed their necessity in aversive and appetitive taste learning. By restricting the expression of chemogenetic receptors in aIC-to-BLA neurons, we demonstrate that activity within the aICto-BLA projection is necessary for both aversive taste memory acquisition and retrieval, but not for its maintenance, nor its extinction. Moreover, inhibition of the projection did not affect incidental taste learning per se, but effectively suppressed aversive taste memory retrieval when applied either during or before the encoding of the unconditioned stimulus for CTA (i.e., malaise). Remarkably, activation of the projection after novel taste consumption, without experiencing any internal discomfort, was sufficient to form an artificial aversive taste memory, resulting in strong aversive behavior upon retrieval. Our results indicate that aIC-to-BLA projecting neurons are an essential component in the ability of the brain to associate taste sensory stimuli with body states of negative valence and guide the expression of valence-specific behavior upon taste memory retrieval.

LTD at amygdalocortical synapses as a novel mechanism for hedonic learning

“…Recent work has identified a role for corticoamygdala projecting neurons in CTA ( Lavi et al, 2018 ; Kayyal et al, 2019 ), suggesting that this population of GC neurons is involved in the acquisition and retrieval of the aversive taste memory. Whether the population of amydala-projecting and amygdala-recipient neurons in GC overlap is currently unknown, but this study raises interesting questions about how and when reciprocal connections between BLA and GC are recruited in CTA.…”

“…In naïve animals, analysis of GC neurons’ activity following inactivation of BLA indicates that amygdalar inputs to GC provide information about the affective dimension of taste stimuli ( Piette et al, 2012 ). Recent studies suggest that the expression of aversive behaviors related to taste depend on the output of GC to the amygdala ( Lavi et al, 2018 ; Schiff et al, 2018 ; Kayyal et al, 2019 ).…”

Cortico-amygdala interaction determines the insular cortical neurons involved in taste memory retrieval

“…In the IC, LTP is induced by the high frequency stimulation of BLA, which modulates CTA memory formation [ 18 – 22 ]. Recently, it is shown that IC-to-BLA projecting neurons are an essential components of the CTA acquisition and memory retrieval [ 26 ]. Consistent with these findings, c-fos expression after memory retrieval was preferentially observed in the IC neurons reciprocally connected to the BLA in our experiment.…”

“…In addition, CTA training induces subsequent LTP in the BLA-IC pathway and increases amygdala-cortical function connectivity [ 23 , 24 ]. Recently, it was shown that IC neurons projecting to the BLA is involved in the CTA memory formation and retrieval [ 25 , 26 ]. However, the mechanism by which a neuronal population encoding CTA memory in the IC is determined is not fully understood.…”

Taste Processing: Insights from Animal Models

“…In addition to lesion studies, other methods and approaches have also pointed to the basolateral amygdala as a selective amygdaloid nucleus mediating the acquisition of CTA. By two-photon calcium imaging it has been revealed that a CTA-dependent neuronal activation of specific neurons of the insular cortex that project to the basolateral amygdala [54], and chemical activation of the insular cortex-basolateral amygdala projection by Clozapine-N-oxide after taste exposure, can induce aversive taste memory in mice [55]. Thus, the function of the basolateral amygdala on CTA might be controlled by afferent axons from the gustatory insular cortex [53].…”