Research Involving Animals – Division of Biomedical Services

An invertebrate model for studies of learning and memory

The observation that some treatments (pharmacological and behavioural) can induce amnesia after a memory has been reactivated (a.k.a., memory reconsolidation) has captured the attention of researchers because it opens the possibility of modifying the strength of previously acquired memories after retrieval. This can shed light on the development of novel therapeutic treatments for trauma-based disorders like PTSD, anxiety disorders, and also drug abuse. However, there are controversial findings and debates across the studies and inconsistencies between laboratories, which obviously hamper the potential translation of these findings to the clinic. Therefore, many have focused on boundary conditions for the observation of this phenomenon, to better understand the mechanisms underlying this process. Yet, there are significant ethical shortcomings in using humans and rodents with available methods causing pain, suffering or lasting distress. 

In order to better understand the underlying mechanisms of memory maintenance and modification, we developed an invertebrate model that can be used as an alternative to vertebrate models. Flatworm planaria (large brown Dugesia) are an ideal candidate because they have a rudimentary nervous system that expresses various neurotransmitter systems (dopamine, serotonin, acetylcholine, GABA) and structural features at the individual neuronal level (e.g., dendritic spines) which are similar to those see in vertebrates and mammals. Moreover, previous research has shown that planaria show mammalian-like behaviours in response to drugs of abuse and natural reinforcers such as sucrose, and develop Conditioned Place Preference (CPP), which is form of Pavlovian learning that establishes long lasting memories. Using this preparation, we observed acquisition, extinction and reinstatement of sucrose CPP. In the current paper, we exposed planaria to pairings of a distinctive surface with sucrose, using a protocol that has previously been validated in the laboratory, and results in a preference for that surface. Following this training, we investigated the amnestic effects of Heat Shock (a known stressor in planaria) following different amounts of memory reactivation (i.e., exposure to the trained surface in the absence of sucrose). We observed that Heat-Shock administered after a short reactivation period (4 sessions) abolished excitatory CPP memory when probed through a sucrose-reinstatement test. When Heat-Shock was administered following 10 sessions of reactivation, we did not find any effect of Heat-Shock in subsequent reinstatement test. However, Heat-Shock administration following a long reactivation period (16 sessions) attenuated the expression of inhibitory memory (surface - no sucrose). Consistent with previous findings in other species, these findings show that excitatory and inhibitory memories interact in complex ways and these may determine the effectiveness of amnestics following memory reactivation. Importantly, we observed that the amount of exposure is a critical variable in determining the effect of the amnestic. Planaria’s breeding and maintenance are of low cost, and high-throughput can be easily achieved. Thus, we believe that planaria is a promising invertebrate model that might bring some further insights into the changes in memory traces after reactivation, whilst reducing the number of rodents used. 

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