Elsevier

Neurobiology of Aging

Volume 32, Issue 6, June 2011, Pages 1149-1156
Neurobiology of Aging

Septo-temporal gradients of neurogenesis and activity in 13-month-old rats

https://doi.org/10.1016/j.neurobiolaging.2009.05.022Get rights and content

Abstract

Recent studies suggest that hippocampal function is partially dissociable along its septo-temporal axis: the septal hippocampus is more critical for spatial processing, while the temporal hippocampus may be more important for non-spatial-related behavior. In young adults, water maze training specifically activates new neurons in the temporal hippocampus, but it is unknown whether subregional differences are maintained in older animals, which have reduced neurogenesis levels. We therefore examined gradients of activity-related Fos expression and neurogenesis in 13-month-old rats and found that neurogenesis occurs relatively evenly throughout the dentate gyrus. Water maze experience significantly increased Fos expression in the suprapyramidal blade and Fos was highest in the septal pole of the dentate gyrus whether the animal learned a platform location, swam in the absence of a platform or remained in their cage. No Fos+ young neurons were found using typical markers of immature neurons. However, Fos expression in the subgranular zone, where adult-born neurons predominate, was disproportionally high in the temporal dentate gyrus. These findings indicate that adult-born neurons in the temporal hippocampus are preferentially activated compared with older neurons.

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).

References (46)

  • A.G. Dayer et al.

    Short-term and long-term survival of new neurons in the rat dentate gyrus

    J. Comp. Neurol.

    (2003)
  • L. de Hoz et al.

    Longitudinal axis of the hippocampus: both septal and temporal poles of the hippocampus support water maze spatial learning depending on the training protocol

    Hippocampus

    (2003)
  • C.L. Dolorfo et al.

    Entorhinal cortex of the rat: topographic organization of the cells of origin of the perforant path projection to the dentate gyrus

    J. Comp. Neurol.

    (1998)
  • M.R. Drew et al.

    Adult hippocampal neurogenesis as target for the treatment of depression

    CNS Neurol. Disord. Drug Targets

    (2007)
  • I. Driscoll et al.

    The aging hippocampus: navigating between rat and human experiments

    Rev. Neurosci.

    (2005)
  • P.W. Frankland et al.

    The organization of recent and remote memories

    Nat. Rev. Neurosci.

    (2005)
  • F.B. Gaarskjaer

    Organization of the mossy fiber system of the rat studied in extended hippocampi. I. Terminal area related to number of granule and pyramidal cells

    J. Comp. Neurol.

    (1978)
  • M. Gallagher et al.

    Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris water maze

    Behav. Neurosci.

    (1993)
  • J.F. Guzowski et al.

    Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles

    Nat. Neurosci.

    (1999)
  • M.R. Hunsaker et al.

    Dissociating the roles of dorsal and ventral CA1 for the temporal processing of spatial locations, visual objects, and odors

    Behav. Neurosci.

    (2008)
  • S. Jessberger et al.

    Adult-born hippocampal neurons mature into activity-dependent responsiveness

    Eur. J. Neurosci.

    (2003)
  • M.W. Jung et al.

    Comparison of spatial firing characteristics of units in dorsal and ventral hippocampus of the rat

    J. Neurosci.

    (1994)
  • N. Kee et al.

    Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus

    Nat. Neurosci.

    (2007)
  • Cited by (29)

    • Consistent within-group covariance of septal and temporal hippocampal neurogenesis with behavioral phenotypes for exploration and memory retention across wild and laboratory small rodents

      2019, Behavioural Brain Research
      Citation Excerpt :

      Adult-born neurons formed at a specific point of the longitudinal axis may contribute to these segregated functionalities [49]. Our findings support this view and are by and large in agreement with reported dissociations between neurogenesis and behavioral traits in the dorsal/septal or ventral/temporal hippocampus in laboratory mice and rats [50–58]. Our data confirm that neurogenesis in the temporal hippocampus covaries positively with a cautious behavioral phenotype.

    • Adult hippocampal neurogenesis for systems consolidation of memory

      2019, Behavioural Brain Research
      Citation Excerpt :

      New neurons that are generated within the DG form synapses and are incorporated into existing HPC circuits [58–62] (Fig. 1). The level of HPC neurogenesis is positively and negatively affected by the environment [16,63], irradiation [19,64], neuronal activity [16,65–69], stress [16,63,70], and aging [16,63,71,72]. Mice with reduced adult neurogenesis in the DG exhibit less contextual fear memory and reduced reactivation of CA3 but not DG neurons that were active during contextual fear conditioning [73].

    • Sex differences in response to chronic mild stress and congenital serotonin deficiency

      2014, Psychoneuroendocrinology
      Citation Excerpt :

      Although our current results did not reveal any significant effects of stress on hippocampal neurogenesis, they do reveal that sex and 5-HT deficiency exhibit a differential impact on cell proliferation along the anterior-posterior dimensions of the hippocampus (at least within the anterior/dorsal/septal two-thirds of the structure). Prior work has shown that the rates of neurogenesis differ along the septo-temporal axis of the hippocampus (Snyder et al., 2009, 2011), but the factors that lead to these regional differences in hippocampal neurogenesis remain poorly defined. Our results identify sex and 5-HT deficiency as two factors regulating regional differences in hippocampal neurogenesis and highlight the possibility that alterations in the regional balance of hippocampal neurogenesis may have important implications for sex- and 5-HT-deficiency-induced behavioral changes.

    • Adult hippocampal neurogenesis: An actor in the antidepressant-like action

      2013, Annales Pharmaceutiques Francaises
      Citation Excerpt :

      Chronic antidepressant treatment can restore the relationship between the hippocampus and the HPA axis, but only in the presence of an intact neurogenic niche. Another study also demonstrates that adult-born hippocampal neurons are required for normal expression of the endocrine and behavioral components of the stress response [38]. Future studies will need to use genetic methods to determine more directly if young neurons impact the negative feedback circuit to the HPA axis.

    • Adult neurogenesis. From circuits to models

      2012, Behavioural Brain Research
      Citation Excerpt :

      Likewise, neurogenesis is more active in dorsal than in ventral hippocampus [22]. Reduction of this gradient, together with reduced absolute levels of neurogenesis during aging, parallels decline in physiological performance of the hippocampus [23]. Any changes in the rate of neurogenesis should take the circuitry of the hippocampus into account.

    View all citing articles on Scopus
    View full text