Brain region specific molecular activity changes in the mouse brain induced by reversal learning
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1
KU Leuven, Laboratory of Neuroplasticity and Neuroproteomics, Belgium
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2
KU Leuven, Laboratory of Biological Psychology, Belgium
Neuroplasticity, a phenomenon that can be defined as the possibility of the nervous system to adapt to new experiences, plays a crucial role in experience-dependent learning. More specifically, reversal learning requires the modulation or adaptation of learned associations and implicates what some authors have called higher-level cognitive processes. Reversal of a navigation task, a type of learning that can be studied in laboratory rodents, modulates previously learned spatial information by subsequent experiences, which most likely establishes new spatial memories as well as inhibits the old ones.
In order to elucidate the contribution of the hippocampus (CA1), the anterior cingulate cortex (aCC) as part of the prefrontal cortex, and striatal subregions including the dorsomedial (DMS) and the dorsolateral (DLS) striatum to this type of learning, adult mice were trained in the Morris water maze (MWM). In this well established visually-guided spatial navigation task mice were trained for 10 days to locate a hidden platform based on distal environmental cues, followed by a reversal protocol of 3 days in which the platform was moved to the opposite quadrant. The involvement of the different brain structures was examined at both the behavioural and molecular level at different time points in the learning curve. The early learning phase, characterized by large and rapid performance gains is represented by the 3 days trained group. Next, we have an advanced learning phase reflected by the 10 days trained group in which subjects had already reached high task proficiency. After translocation of the platform, the course of reversal learning was visualized by three time points: the first and last trial of the first reversal day and 3 days reversal training. Our results indicate an increase in path length during the first trial of reversal compared to the day 10 group. However, after 3 days reversal learning, animals were as proficient in finding the new platform location as 10 days trained animals were in locating the initial platform position.
All learning-related neuronal activity changes in the five aforementioned groups were mapped by in situ hybridization for the immediate early gene zif268, an activity reporter gene.
From day 3 to day 10 in the MWM training the zif268 expression remained unchanged in the aCC, CA1 and DLS. In DMS however we observed a significant decrease. Upon reversal (initial trial of the first reversal day), zif268 expression decreased in all analyzed brain areas.
By the fourth trial on the first day of reversal zif268 expression levels in aCC, CA1, DMS and DLS already returned to the levels reached at day 10 of the MWM. Also, these levels were sustained after 3 days reversal learning.
In conclusion, we demonstrated the most pronounced changes in the activity of several brain regions after the initial reversal trial. Activity levels at this learning stage were consistently lower compared to mice trained for 10 days to locate the previous platform position and mice trained for 3 days to find the new platform location.
Keywords:
Morris water maze,
Reversal Learning,
brain plasticity,
Striatum,
Hippocampus,
Prefrontal Cortex,
Immediate Early Gene (IEG)
Conference:
Belgian Brain Council, Liège, Belgium, 27 Oct - 27 Oct, 2012.
Presentation Type:
Poster Presentation
Topic:
Higher Brain Functions in health and disease: cognition and memory
Citation:
Ytebrouck
E,
Ceulemans
A,
Laeremans
A,
Van Den Bergh
G,
D'Hooge
R and
Arckens
L
(2012). Brain region specific molecular activity changes in the mouse brain induced by reversal learning.
Conference Abstract:
Belgian Brain Council.
doi: 10.3389/conf.fnhum.2012.210.00035
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Received:
10 Sep 2012;
Published Online:
12 Sep 2012.
*
Correspondence:
Prof. Lutgarde Arckens, KU Leuven, Laboratory of Neuroplasticity and Neuroproteomics, Leuven, Vlaams-Brabant, 3000, Belgium, Lut.arckens@kuleuven.be