Endocannabinoids disrupt stressed snails’ memories

Abstract

Life has never been easy, and the physical mechanisms that were evolved by the earliest life forms for protection are fundamental to survival even today. However, fast-forward to our 24/7 news-saturated millennial culture and those stress systems are saturating. ‘We all know that when we are under stress we perform differently’, says Ken Lukowiak, from the University of Calgary, Canada, who is investigating the impact of stress on memory. However, instead of trying to untangle the complex networks that underpin human memory, Lukowiak and his colleagues focus on the memory of a simpler creature, pond snails (Lymnaea stagnalis); more specifically, the memory to hold their breath and not extend their breathing tubes above the surface when the water in which they reside is low in oxygen. Explaining that one molecular system – the endocannabinoid system – in our brains is thought to be a key player in mediating stress, disrupting our ability to form memories, Lukowiak, Hiroshi Sunada and their colleague Etsuro Ito, from Waseda University, Japan, wondered whether their humble pond snails also used the same system and, if so, how it affected their ability to form memories. But first they had to find the receptor molecules that could mediate endocannabinoid effects in the snails.Searching a database of the pond snail's genes with the sequence of a cannabinoid receptor that had been identified in the vase tunicate sea squirt, Takayui Watanabe, from the University of Sapporo, and Dai Hatakeyam identified two candidates, before confirming that both of the genes are expressed to produce the necessary receptors, not only in the snail's nervous system, but also in other tissues. In addition, they found more of the second receptor produced in the nervous system than the first receptor, which was more widely distributed throughout the snail's body. Next, the team investigated whether the receptors could disrupt the snail's ability to form memory.Injecting the snails with a drug that is known to trigger the endocannabinoid receptor and disrupt memory formation in mammals, Sunada, Sangmin Lee and Jeremy Forest then trained the molluscs to keep their breathing tubes closed when their water was deoxygenated – by poking the breathing tubes with a toothpick whenever the snails tried to stick them out of the water – to find out whether the snails could still form a memory: but they did not. And when Sunada, Lee and Forest tested whether a traumatic experience would also block the snails’ memories – by jabbing them on the foot before breath-hold training – the snails were equally unable to learn and form the new memory. However, when the team administered a drug that could block the endocannabinoid receptors from disrupting memory formation 1 h before traumatising the snails, this time the snails were able to learn to keep their breathing tubes closed when the water was deoxygenated and they wanted to pop up for air.The stressful jabbing experience had the same effect on the snails' memories as the drug that triggered the endocannabinoid receptor, making it likely that the endocannabinoid receptor was activated by stress to disrupt memory formation. Lukowiak says, ‘We feel pretty confident that this [the endocannabinoid] system in the snail plays a major role in determining how stress alters memory formation’, and he adds, ‘We think that it plays an important role in determining the “state” of the animals and thus whether a specific stimulus will be regarded as a stressor’.