Inflammatory modulation of learning and memory- A role for hippocampal neurogenesis?
Neurogenesis is the birth of new neurons. It is a multistep process which consists of asymmetric division of neural stems ultimately leading to the generation of new neurons. In the hippocampus, neurogenesis occurs predominantly during embryonic development and also during adulthood (Altman and Das, 1965). In the human brain, adult neurogenesis occurs in the subgranular zone of the dentate gyrus throughout life (Eriksson et al., 1998). Newly formed cells in the subgranular layer then migrate to the granular layer of the dentate gyrus where they express a neuronal phenotype (Kuhn et al., 1996). These adult-formed granule cells are integrated into the existing hippocampal circuitry where they participate in hippocampal function after several weeks (Jessberger and Kempermann, 2003).
The role of hippocampal neurogenesis in learning and memory
The extent in which hippocampal neurogenesis plays a role in learning and memory is an active area of research. Evidence suggests that learning enhances adult hippocampal neurogenesis. The effects of associative learning on hippocampal neurogenesis in adult rats were determined by labelling new cells with the thymidine analogue bromodeoxyuridine (BrdU) and analysing these cells after specific behavioural tasks. The number of BrdU labelled cells dramatically increased in the dentate gyrus following specific hippocampus-dependent tasks whereas there was no significant increase after completing hippocampus-independent tasks (Gould et al., 1999).
The object location test (OLT) is a behavioural test to assess the ability of a rodent to differentiate between a familiar and novel spatial location. Rodents with hippocampal lesions are impaired in this specific test, suggesting a role for the hippocampus (Ennaceur et al., 1997). There is evidence to suggest that a reduction in adult hippocampal neurogenesis impairs spatial memory in the hippocampal dependent object location task. Methylazoxymethanol (MAM) is an antimitotic agent (Johnston and Coyle, 1979) that was used to reduce the number of young granule cells before the object location test was carried out. The mice were placed in an open-field square which had a striped pattern on one wall of the field. Two identical objects were placed in the field. The test consisted of an exploration phase and a test phase. During the exploration phase the MAM treated mice as well as the control mice spent the same amount of time exploring the objects. However during the test phase, in which one object was moved to a new location, the MAM treated mice spent a significantly less amount of time exploring the object in the new location in comparison to the control mice. This suggests that the MAM treated mice were unable to discriminate between the novel and familiar location (Goodman et al., 2010).
The Morris Water Maze (MWM) is a behavioural test that can test the...