Septo-temporal gradients of neurogenesis and activity in 13-month-old rats
Introduction
While a role for the hippocampus in spatial memory is well established (Frankland and Bontempi, 2005), more recent evidence also points to a role for the hippocampus in regulating anxiety-related behavior. There is substantial evidence suggesting that these two functions of the hippocampus are at least partially subserved by different anatomical subregions: the septal hippocampus is particularly important for spatial learning and the temporal hippocampus regulates defensive, anxiety-related, and odor-mediated behaviors (Bannerman et al., 2004, Pentkowski et al., 2006, Hunsaker et al., 2008). Other studies suggest that the temporal hippocampus contributes to spatial learning as well, but to different aspects than the septal hippocampus, including processing larger spatial environments (Jung et al., 1994, Kjelstrup et al., 2008), learning over longer timescales (de Hoz et al., 2003), and mediating context-based inhibitory associations (McDonald et al., 2006). Thus, the function of the temporal hippocampus in regulating anxiety and spatial processing appears to differ from that of the septal hippocampus.
Given the septo-temporal functional dissociation, and findings suggesting that adult neurogenesis in the hippocampus is involved in both spatial learning and anxiety-related behavior (Leuner et al., 2006, Drew and Hen, 2007), we previously examined septo-temporal gradients (there referred to as “dorso-ventral” gradients) of neurogenesis and activity (i.e. Fos+ cells) in young neurons in young adult rats after learning in a spatial water maze task (Snyder et al., 2009). In that study, both neurogenesis and granule neuron Fos expression were higher in the septal dentate gyrus of the hippocampus. However, expression of Fos by young neurons after water maze training was specific for the temporal dentate gyrus, suggesting that young granule neurons may play a different role than older granule neurons in water maze learning.
It is well documented that neurogenesis declines with age (Altman and Das, 1965, Seki and Arai, 1995, Kuhn et al., 1996, McDonald and Wojtowicz, 2005), and there are also reports that the expression of activity-dependent immediate early genes (IEGs) is reduced with age (Small et al., 2004). However, it is unclear whether there are changes in septo-temporal gradients of neurogenesis and activity with aging, which could alter distinct aspects of hippocampus-dependent learning in old age. Therefore, in the current study, we examined neurogenesis and water maze-induced Fos expression in septo-temporal and infrapyramidal-suprapyramidal axes of the dentate gyrus in 13-month-old rats. We found weak subregional differences in levels of neurogenesis but strong biases for Fos expression in the septal dentate gyrus and in the suprapyramidal blade after water maze experience. In the temporal dentate gyrus, but not septal dentate gyrus, water maze training activated adult-born neurons (in the subgranular zone) more than older neurons (in the outer rows).
Section snippets
Animals and treatments
Fourteen 13-month-old male Long Evans rats (Charles River, Quebec) were used in the following experiments. All animals were individually housed, and all treatments conformed to animal health and welfare guidelines of the University of Toronto. To label adult-born DG granule cells, all rats were given 2 intraperitoneal injections of 5-bromo-2′-deoxyuridine (BrdU; Sigma, 50 mg/kg/injection, dissolved at 20 mg/ml in saline, 0.007N NaOH) spaced 10 h apart, for 5 consecutive days. Beginning 3 weeks
Water maze behavior
Rats showed a decreased latency to find the hidden platform over 4 blocks of trials in the water maze, indicating rapid acquisition of spatial information (repeated measures ANOVA, main effect of block, F3,21 = 9.9, p < 0.001; Fig. 1A). The latency for block 1 was significantly higher than all other blocks (post hoc, p < 0.05 for all) and blocks 2, 3 and 4 were not different from each other (p > 0.05). To verify that decreases in latency reflected spatial search strategies, the mean distance
Neurogenesis gradients and aging
No suprapyramidal-infrapyramidal gradient in neurogenesis was observed in these 13-month-old rats. A significant septo-temporal gradient was observed but only in the mid-septal quadrant; the septal pole showed levels of neurogenesis identical to that in the temporal pole. This contrasts with young adults, which have higher neurogenesis in the infrapyramidal blade than in the suprapyramidal blade and twice as much neurogenesis in the septal pole than in the temporal pole (Snyder et al., 2009),
Disclosure statement
The authors declare no actual or potential conflicts of interest regarding this work.
Acknowledgements
This work was funded by an Ontario Graduate Scholarship (JSS), the Canadian Institutes of Health Research (JMW) and the Intramural Program of the National Institute of Mental Health, Z01-MH002784 (HAC).
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