Strong Aversive Conditioning Triggers a Long-Lasting Generalized Aversion

Abstract

Generalization is an adaptive mnemonic process in which an animal can leverage past learning experiences to navigate future scenarios, but overgeneralization is a hallmark feature of anxiety disorders. Therefore, understanding the synaptic plasticity mechanisms that govern memory generalization and its persistence is an important goal. Here, we demonstrate that strong CTA conditioning results in a long-lasting generalized aversion that persists for at least 2 weeks. Using brain slice electrophysiology and activity-dependent labeling of the conditioning-active neuronal ensemble within the gustatory cortex, we find that strong CTA conditioning induces a long-lasting increase in synaptic strengths that occurs uniformly across superficial and deep layers of GC. Repeated exposure to salt, the generalized tastant, causes a rapid attenuation of the generalized aversion that correlates with a reversal of the CTA-induced increases in synaptic strength. Unlike the uniform strengthening that happens across layers, reversal of the generalized aversion results in a more pronounced depression of synaptic strengths in superficial layers. Finally, the generalized aversion and its reversal do not impact the acquisition and maintenance of the aversion to the conditioned tastant (saccharin). The strong correlation between the generalized aversion and synaptic strengthening, and the reversal of both in superficial layers by repeated salt exposure, strongly suggests that the synaptic changes in superficial layers contribute to the formation and reversal of the generalized aversion. In contrast, the persistence of synaptic strengthening in deep layers correlates with the persistence of CTA. Taken together, our data suggest that layer-specific synaptic plasticity mechanisms separately govern the persistence and generalization of CTA memory.

Conditioning by a Previous Experience Impairs the Rewarding Value of a Comfort Meal

“…Our conditioning paradigm introduced a colour clue (coloured meal during and after conditioning versus non-coloured meal pre-conditioning), but we do not know whether conditioned postprandial dissatisfaction was selective to the colour or if it would also affect the non-coloured meal; indeed, other forms of conditioning express generalisation and affect related stimuli [ 33 , 34 ].…”

“…Furthermore, only women were included and the effect of conditioning on men remains to be explored. This pilot study, proving a new concept, opens a series of questions, particularly in relation to the specificity versus generalisation of the conditioned response, extinction interval and the relation between aversive stimulus/conditioned response [30,33,34], that remain to be addressed.…”

Effects of exposure to novel taste stimuli on taste aversive conditioning (TAC) in rats / Efectos de la exposición a estímulos gustativos novedosos sobre el condicionamiento aversivo a sabores (CAS) en ratas

“…Por otro lado, puede presentarse un fenómeno denominado generalización de estímulos, pero aún no está claro cuánto tiempo puede mantenerse la generalización resultante del CAS y tampoco se conoce cuáles son los factores que influyen en su duración. Se ha reportado que un condicionamiento moderado (concentración baja de LiCl, 0.15 M, 1 ml/100 g de peso corporal, a través de inyecciones intraperitoneales) induce una generalización que puede revertirse en 24 horas en comparación con un condicionamiento fuerte (concentración más alta de LiCl, 0.30 M), que puede estar presente de 24 horas hasta dos semanas después (Bures et al, 1998;Ramos et al, 2022).…”

Reversal of Conditioned Food Aversion Using a Cognitive Intervention: A Sham-Controlled, Randomized, Parallel Study

“…As a result, conditioning by exposure to this meal blunted the postprandial hedonic response to the comfort meal, but it did not affect homeostatic sensations, and did not induce nausea or abdominal pain; furthermore, conditioning reduced meal liking but did not induce real taste aversion. It remains uncertain whether cognitive intervention may revert stronger food aversions with homeostatic or emotive components, which are more resistant to extinction [19,20].…”

“…However, in the control group, the response to the regular-fat meal on the fourth day induced an aversive response even without the colour label, indicating that conditioning was not colour-specific. It has been previously shown that other forms of conditioning affect related stimuli by a phenomenon of generalization [19,21].…”