Conditioned Taste Aversion Depends on Long-Term Depression of Neuronal Signaling

Vignesh Subramanian ’24

Figure 1: The amygdala, a collection of nuclei deep within the temporal lobe of the human brain, integrates and processes emotional, behavioral, and memory-based inputs. 

Conditioned taste aversion (CTA) is a learned association, made by humans as well as other animals, between the taste of food consumed and a subsequent period of illness assumed to be caused by said consumption. This period of illness is paired with an aversive stimulus, such as gastrointestinal malaise, and produces visceral distress that encourages the animal to avoid the food in question. CTA is considered an adaptive, evolutionarily developed trait, with the survival response activated by signaling in the gustatory portion of the insular cortex (GC) as well as the basolateral nucleus of the amygdala (BLA) of the animal’s brain. However, the underlying synaptic connections and expression of contributing genes are poorly understood. A study led by Dr. Arianna Maffei of Stony Brook University aimed to better characterize the relationship between amygdalocortical synaptic efficacy and hedonic, or sensation-based, learning as they collectively establish CTA in animals.

The researchers first trained male and female Long Evans rats in a CTA paradigm involving sucrose solution diets paired with gastric malaise-inducing intraperitoneal injections of lithium chloride. These subjects were then submitted to conditioning sessions and 2-bottle tests to assess their learning and consolidation of the aversive memory based on rates of solution consumption. Finally, a combination of whole-cell patch clamp recordings, selective optogenetic activations of terminal fields, and immediate early gene immunohistochemistry was utilized to assess stimulus patterns and circuit plasticity, or the ability to modify the strength of a synapse, among the involved signaling neurons.

It was found that the establishment of CTA learning is largely dependent on synaptic long-term depression (LTD), a process in which neuronal signaling responses are decreased in amplitude, or reduced, for extended periods. While CTA directly reduced activity in the GC, LTD was also detected at BLA synapses onto pyramidal neurons in the GC, confirming the crucial role of the BLA-to-GC signaling pathway in establishing CTA. Additionally, it was found that low stimulation of BLA terminal fields is sufficient to change the hedonic value of a taste stimulus. Collectively, these findings provide the first known evidence that such plasticity at amygdalocortical synapses can alter the degree of ‘unpleasantness’ expressed by the sensory stimulus in the two regions, and reveal that CTA learning-induced circuit changes rely on decreases in synaptic input rather than the strengthening of remodeled connections. 

Works Cited:

[1] A. Maffei, et al., LTD at amygdalocortical synapses as a novel mechanism for hedonic learning. eLife 9, 1–21 (2020). doi: 10.7554/eLife.55175

[2] Image retrieved from:


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