Decision letter: A molecular mechanism underlying gustatory memory trace for an association in the insular cortex

Abstract

The survival of animals, including us humans, depends on the ability to discriminate good food from bad. We would prefer eating a given taste if it did not cause any negative feelings after eating it for the first time; however, we would avoid eating that specific taste if it caused any digestive discomfort. This ability to connect sensory events that happen close in time is called associative learning. One longstanding theory of associative learning suggests that if the neurons that are activated by a taste fire at the same time as those that control nausea, the connections between the two groups of neurons are strengthened. This helps that particular taste to become associated with the feeling of illness. Animals can also link events that are separated in time – for example, they can become averse to a food even when its ill effects are felt several hours after eating it. An important question is how a new event (such as a new food) is internally represented and maintained for a certain time so that it associates with a response (sickness) that occurs much later. One method used to investigate associative learning is to feed rats a new food, and then later make them feel nauseous to measure how much this causes them to avoid the food in the future. The gustatory cortex is the part of the brain responsible for perceiving taste. Chinnakkaruppan and Rosenblum now use this experimental method to investigate the molecular mechanisms in the gustatory cortex that enable the internal representation (or memory trace) of a new taste to be associated with an unwell feeling that occurs much later. The results of the experiments show that rats will avoid food with a certain flavor if they feel unwell within eight hours of eating it. However, the response of the rats differs depending on when the rat becomes ill. Underpinning these behaviors is the formation of two parallel internal representations of the new taste: a short-term, robust trace that lasts for three hours; and a parallel, longer lasting, weaker trace that lasts for eight hours to associate the taste with its outcome. The weaker, longer-lasting memory trace only forms if the shorter, stronger trace also occurs. Chinnakkaruppan and Rosenblum found that forming the shorter, stronger memory requires the activity of a signaling pathway in the gustatory cortex that involves biochemical molecules called NMDAR-CaMKII-GluA1. These molecules can increase the strength of signaling between neurons and are already implicated in learning and memory. The next challenge is to put this newly identified molecular mechanism within the relevant neural circuit in the gustatory cortex.