Level of Individual Differences in a Population of Sprague Dawely Rats in a Behavioral Test Battery and Effect of Dopaminergic Signaling Modulation on Spatial Reference Memory as well as Prefrontal Cortex Protein Expression

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Addis Abeba University


Level of Individual Differences in a Population of Sprague Dawely Rats in a Behavioral Test Battery and Effect of Dopaminergic Signaling Modulation on Spatial Reference Memory as well as Prefrontal Cortex Protein Expression Daniel Daba Feyissa, Addis Ababa University, 2019 Spatial reference memory is known to be modulated by the dopaminergic system involving different brain regions with projections to the hippocampus. The roles of dopamine type 1 and 2 receptors are reported to be different upon learning or memory in an activation and task dependent manner. While the hippocampus is traditionally considered a key structure in the formation of spatial memories, recent data has converged on the importance of its connections to the prefrontal cortex supporting memory consolidation, as well as controlling memory retrieval. However, the role of dopamine signaling on prefrontal cortex-mediated spatial reference memory consolidation, and especially on proteomic changes after learning tasks, remains poorly investigated. On the other hand, different early pre-and postnatal experiences and environmental complexity support individual behavior, physiology, and molecular processes during adulthood. For these reasons, it is difficult to generalize between different laboratories but individuality should be estimated for each local population of animals and may then provide more reliable results in animal models of mental and cognitive diseases and individual vulnerability. The current research is focused on investigation of the role of dopamine type 1 and 2 like receptor signaling on spatial reference memory in “simple” and “difficult” hole-board paradigm as well as the change in proteomic landscape in prefrontal cortex. Furthermore, the current research helps to investigate the level of individual differences in a given population of SpragueDawley rats which may indirectly provide some evidences about whether dopaminergic signaling improves spatial reference learning and memory through direct effect or through increasing motivation of animals for search of the reward. Briefly for the investigation of the level of individual differences in a population of SpragueDawley rats, 162 naïve rats were underwent a behavioral test battery including commonly used test paradigm for spatial learning and memory (hole-board) and different behavioral patterns test paradigms such as open field, elevated plus maze, forced swim test as well as rota rod for motor abilities. And to assess the contribution of D 1 and D -like dopamine receptor signaling on spatial learning and memory in a food rewarded hole-board task, a canula was implanted surgically into right side lateral ventricle of 60 rats’ age 12-13 weeks. The rats were grouped into 6 groups with 10 rats each. The first four groups were treated with SKF-81297 (1μg and 5μg) and Sumanirole 2 (1μg and 5μg) through intracerebroventricular infusion once 30 min prior to daily training sessions. The other two groups were treated with 1μg of SCH 23390 and Remoxipride following similar procedure. D1 agonist at one dosage (5µg) was used in a more demanding hole-board task. In addition, proteomics studies were carried out to identify proteins that could be influenced by the dopaminergic signaling during the spatial reference memory acquisition and consolidation in a more demanding hole-board task. The high dimensional behavioral results from behavioral test batteries mentioned above were reduced to fewer components associated with spatial cognition, motivation, anxiety and depression-like behaviors. The behavioural battery test indicated that, 24 % showed a high, 19 % a low and 57 % an intermediate intrinsic state of motivation. The largest 'low' portion (41%) was given for the factor cognition and the largest 'high' portion (29%) for the intrinsic anxiety. Thus, almost every third rat was intrinsically at a high level in the population. Because the animals were intact, untreated and experimentally naïve the results reflect trait patterns of behavior and thus individuality. On the other hand, the hole-board spatial reference memory assessment revealed that D1R agonism induced persistent enhancement of performance, whereas D1R antagonism had no significant effect on spatial reference memory formation. D2R agonist and antagonist exerted no effects. Phase specific comparisons revealed an enhancement of spatial acquisition in the presence of the D1R but not D2R agonism on acquisition, but not during retention. The D1R agonist tested in the hole-board task with increased “difficulty” revealed that D1R agonist treated animals performed significantly better during all training phases, with results better resolved than in the “easy” task. Additionally, proteomic analysis of the prefrontal cortex revealed ninety six proteins to be regulated by D1R agonism, from which 35 were correlated with behavioral performance. Obtained targets were grouped by function, showing synaptic transmission, synaptic remodeling, and dendritic spine morphology as the major functional classes affected. The behavioral test batteries pointed out that an experimenter recruiting experimental samples can expect about ≥24 % probability to have intrinsically high animals in terms of anxiety, cognitive, motivation and depressive like behaviours in the sample. Furthermore, activation of D1R signaling during spatial acquisition and consolidation improved reference memory index depending on the task difficulty, with greater effect in a “difficult” task and altered the proteome landscape of the prefrontal cortex indicative of massive organizational synaptic restructuring.



Learning , Memory,Memory Consolidation,Memory and Prefrontal Cortex