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
No Thumbnail Available
Date
2019-12
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Addis Abeba University
Abstract
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.
Description
Keywords
Learning , Memory,Memory Consolidation,Memory and Prefrontal Cortex