Generalisation and Novelty in the Egocentric Reversal Learning Task
In some variants of the task used here, animals were challenged with choice of a previously experienced response-arm and a novel response-arm. Animals may have generalised between the 90° and 45° turns in the same direction that were used to generate novel alternatives, and such generalisation would result in the perseverance and learned non-reward tests resembling tests of full reversal learning. However the test condition-dependent effects of SB242084-treated and 5-HT2CR KO mice, as well as the significantly increased number of trials required and larger number of incorrect responses made in the full reversal test than the learned non-reward and perseverance tests of the SB242084 experiment, suggest that animals perceived a 45° shift in arm location as novel. In Experiment 3, which relied on measures of unconditioned exploratory behaviour, a 45° shift in arm location led to significant increases in time spent and entries made into that arm, also suggesting it was recognised as novel.
Treatment-dependent changes in response to novelty may also affect performance in this task. The novel response arm is correct in the perseverance test but incorrect in the learned non-reward test. Increased novelty attraction would therefore facilitate learning in the perseverance test where the novel arm is correct, and retard learning in the learned non-reward test, where the novel arm is incorrect. Thus, one potential explanation for the pattern of results in the SB242084 experiment is that 5-HT2CR antagonism enhances responding for a novel choice in the maze. However, we are unaware of prior evidence for a role of the 5-HT2CR in novelty attraction or novelty recognition. SB242084 also failed to affect performance in the novelty recognition test (Experiment 3), suggesting the observed effects on cognitive flexibility (Experiment 1) instead are related to the ability to overcome previously learned contingencies of reward and non-reward.
Although the discrepant effects in visuospatial and egocentric tasks are most likely due to the tasks tapping different brain-regions and subpopulations of the 5-HT2CR, there are substantial differences in the two types of tasks. Additional to the use of different discriminanda, the current egocentric task involves perseverance to a greater extent than visuospatial reversal learning in the mouse [16]. The current protocol also involves less discrimination training than a visuospatial protocol in the rat [15], [30].