Muscarinic Cholinergic Neuromodulation Reduces Proactive Interference Between Stored Odor Memories During Associative Learning in Rats
Eve De Rosa, Michael E. Hasselmo
Behavioral Neuroscience (2000)
DOI: 10.1037//0735-7044.114.1.32
Brief summary: Rosa and Hasselmo shown that the injection of a central muscarinic receptor antagonist (scopolamine) intraperitoneally, at a low dose, made rats specifically more susceptible to the proactive interference (PI) by previously learned associative memory. The injection of scopolamine at a higher dose led to a general deficits in learning a two-odor discrimination task.
This is a typical hypothesis- and model- driven study. As the authors stated: ‘A computational model, based on this physiological evidence,suggests that when ACh induces these effects on the cortex, it may act to reduce interference between associated items stored in memory‘. In fact, the previous modeling work was done by Hasselmo and his colleagues. Based on the prediction of the model, they deployed the current study. To specifically test acetylcholine’s role in PI, they designed an two-odor discrimination task. In this task, rats were trained to discriminate multiple pair-odors. Firstly, rats were trained to learn one odor pair. Let’s say A+B- (A is rewarded, B is non-rewarded). Within each trial, two odors were delivered simultaneously and independently from two ports and only one of them was rewarded. Rat was required to poke the rewarded port (A+) to get reward. After learning the first odor-pair, rats were trained to learn two more odor pairs: A-C+ or D-E+. Because rats previously learned that A was rewarded, so it was more challenging for them to discriminate A-C+ comparing to that of D-E+. This phenomenon was defined as proactive interference (PI), which meant that the previous memory will interfere the formation of associated new memory. In line with the prediction, they observed that the injection of the antagonist of acetylcholine muscarinic receptors intraperitoneally specifically impaired the learning under the conditions with PI (A-C+), but not a totally new odor-pair (D-E+). The results confirmed the functional role of acetylcholine in reducing the PI effects under physiological conditions.
Although we can criticize the thoroughness of the experiments, the strategy underneath is still inspiring. It also manifests the value of computational modeling in neuroscience investigations.
