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Behavioral experience induces zif268 expression in mature granule cells but suppresses its expression in immature granule cells.

Huckleberry KA, Kane GA, Mathis RJ, Cook SG, Clutton JE, Drew MR - Front Syst Neurosci (2015)

Bottom Line: The immediate-early gene (IEG) zif268 appears to be an important mediator of these effects, as its expression can be induced by neural activity and knockout of zif268 impairs survival of adult-born neurons (Richardson et al., 1992; Veyrac et al., 2013).In summary, behavioral experience transiently activated expression of zif268 in mature granule cells but caused a more long-lasting suppression of zif268 expression in immature, adult-born granule cells.We hypothesize that zif268 suppression inhibits memory-related synaptic plasticity in immature neurons or mediates learning-induced apoptosis of immature adult-born neurons.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Center for Learning and Memory, University of Texas at Austin Austin, TX, USA.

ABSTRACT
Thousands of neurons are born each day in the dentate gyrus (DG), but many of these cells die before reaching maturity. Both death and survival of adult-born neurons are regulated by neuronal activity in the DG. The immediate-early gene (IEG) zif268 appears to be an important mediator of these effects, as its expression can be induced by neural activity and knockout of zif268 impairs survival of adult-born neurons (Richardson et al., 1992; Veyrac et al., 2013). Despite the apparent importance of zif268 for adult neurogenesis, its behavior-induced expression has not been fully characterized in adult-born neurons. Here we characterize behavior-evoked expression of zif268 in mature and newborn dentate granule cells (DGCs). We first quantified zif268 expression in doublecortin-positive (DCX+) immature neurons and in the general granule cell population after brief exposure to a novel environment (NE). In the general granule cell population, zif268 expression peaked 1 h after NE exposure and returned to baseline by 8 h post-exposure. However, in the DCX+ cells, zif268 expression was suppressed relative to home cage for at least 8 h post-exposure. We next asked whether suppression of zif268 in DCX+ immature cells occurs in other behavioral paradigms that recruit the hippocampus. Exposure to Morris water maze (MWM) training, an enriched environment, or a NE caused approximately equal suppression of zif268 expression in DCX+ cells and approximately equal activation of zif268 expression among the general granule cell population. The same behavioral procedures activated zif268 expression in 6-week-old BrdU-labeled adult-born neurons, indicating that zif268 suppression is specific to immature neurons. Finally, we asked whether zif268 suppression varied as a function of age within the DCX+ population, which ranges in age from 0 to approximately 4 weeks. NE exposure had no significant effect on zif268 expression in 2- or 4-week-old BrdU-labeled neurons, but it significantly suppressed zif268 expression in 3-week-old neurons. In summary, behavioral experience transiently activated expression of zif268 in mature granule cells but caused a more long-lasting suppression of zif268 expression in immature, adult-born granule cells. We hypothesize that zif268 suppression inhibits memory-related synaptic plasticity in immature neurons or mediates learning-induced apoptosis of immature adult-born neurons.

No MeSH data available.


Related in: MedlinePlus

Novel environment (NE) exposure activates zif268 expression in mature dentate granule cells (DGCs) but suppresses zif268 expression in immature DGCs. (A) Mice were exposed to a novel environment for 10 min and euthanized 1 h (n = 7), 3 h (n = 7), or 8 h (n = 6) later. An additional group was euthanized immediately after being removed from the home cage (HC; n = 6). (B,C) Representative images of DCX and zif268 immunohistochemistry. Scale bars = 27 μm (B) and 9 μm (C). (D) The total number of DCX+ cells did not differ among experimental conditions (F(3,22) = 2.399, p = 0.095). (E) Total number of zif268+ cells in the granule cell layer (GCL) in HC and NE-exposed mice. NE exposure caused a significant increase in the number of DGCs expressing zif268 as compared to HC (F(3,22) = 3.961, p = 0.021). Zif268 expression peaked 1 h after NE exposure. (F) Percentage of DCX+ cells expressing zif268 in HC and NE-exposed mice. The number of DCX+ cells expressing zif268 was significantly reduced as compared to the HC group (t(24) = 2.520, p = 0.019) for at least 8 h after NE exposure. *p < 0.05.
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Figure 1: Novel environment (NE) exposure activates zif268 expression in mature dentate granule cells (DGCs) but suppresses zif268 expression in immature DGCs. (A) Mice were exposed to a novel environment for 10 min and euthanized 1 h (n = 7), 3 h (n = 7), or 8 h (n = 6) later. An additional group was euthanized immediately after being removed from the home cage (HC; n = 6). (B,C) Representative images of DCX and zif268 immunohistochemistry. Scale bars = 27 μm (B) and 9 μm (C). (D) The total number of DCX+ cells did not differ among experimental conditions (F(3,22) = 2.399, p = 0.095). (E) Total number of zif268+ cells in the granule cell layer (GCL) in HC and NE-exposed mice. NE exposure caused a significant increase in the number of DGCs expressing zif268 as compared to HC (F(3,22) = 3.961, p = 0.021). Zif268 expression peaked 1 h after NE exposure. (F) Percentage of DCX+ cells expressing zif268 in HC and NE-exposed mice. The number of DCX+ cells expressing zif268 was significantly reduced as compared to the HC group (t(24) = 2.520, p = 0.019) for at least 8 h after NE exposure. *p < 0.05.

Mentions: First we assessed the time-course of zif268 expression in dentate granule cells (DGCs) after exposure to a novel environment (NE), a manipulation previously demonstrated to robustly induce IEG expression in DGCs (Clark et al., 2012). Mice were euthanized directly from the home cage (n = 6) or 1 (n = 7), 3 (n = 7), or 8 h (n = 6) after a 10-min exposure to a NE (Figure 1A). DCX expression was used to identify immature, adult-born neurons. We quantified overall zif268 expression in the general granule cell population as well as co-labeling of DCX with zif268 (Figures 1B,C). NE exposure caused a significant increase in the total number of zif268+ cells in the DG (F(3,22) = 3.961, p = 0.021; Figure 1E). Pairwise comparisons revealed that the total number of zif268+ cells at 1 h post-exposure exceeded the home cage and 8 h levels (p’s ≤ 0.014); the other comparisons did not reach significance.


Behavioral experience induces zif268 expression in mature granule cells but suppresses its expression in immature granule cells.

Huckleberry KA, Kane GA, Mathis RJ, Cook SG, Clutton JE, Drew MR - Front Syst Neurosci (2015)

Novel environment (NE) exposure activates zif268 expression in mature dentate granule cells (DGCs) but suppresses zif268 expression in immature DGCs. (A) Mice were exposed to a novel environment for 10 min and euthanized 1 h (n = 7), 3 h (n = 7), or 8 h (n = 6) later. An additional group was euthanized immediately after being removed from the home cage (HC; n = 6). (B,C) Representative images of DCX and zif268 immunohistochemistry. Scale bars = 27 μm (B) and 9 μm (C). (D) The total number of DCX+ cells did not differ among experimental conditions (F(3,22) = 2.399, p = 0.095). (E) Total number of zif268+ cells in the granule cell layer (GCL) in HC and NE-exposed mice. NE exposure caused a significant increase in the number of DGCs expressing zif268 as compared to HC (F(3,22) = 3.961, p = 0.021). Zif268 expression peaked 1 h after NE exposure. (F) Percentage of DCX+ cells expressing zif268 in HC and NE-exposed mice. The number of DCX+ cells expressing zif268 was significantly reduced as compared to the HC group (t(24) = 2.520, p = 0.019) for at least 8 h after NE exposure. *p < 0.05.
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Figure 1: Novel environment (NE) exposure activates zif268 expression in mature dentate granule cells (DGCs) but suppresses zif268 expression in immature DGCs. (A) Mice were exposed to a novel environment for 10 min and euthanized 1 h (n = 7), 3 h (n = 7), or 8 h (n = 6) later. An additional group was euthanized immediately after being removed from the home cage (HC; n = 6). (B,C) Representative images of DCX and zif268 immunohistochemistry. Scale bars = 27 μm (B) and 9 μm (C). (D) The total number of DCX+ cells did not differ among experimental conditions (F(3,22) = 2.399, p = 0.095). (E) Total number of zif268+ cells in the granule cell layer (GCL) in HC and NE-exposed mice. NE exposure caused a significant increase in the number of DGCs expressing zif268 as compared to HC (F(3,22) = 3.961, p = 0.021). Zif268 expression peaked 1 h after NE exposure. (F) Percentage of DCX+ cells expressing zif268 in HC and NE-exposed mice. The number of DCX+ cells expressing zif268 was significantly reduced as compared to the HC group (t(24) = 2.520, p = 0.019) for at least 8 h after NE exposure. *p < 0.05.
Mentions: First we assessed the time-course of zif268 expression in dentate granule cells (DGCs) after exposure to a novel environment (NE), a manipulation previously demonstrated to robustly induce IEG expression in DGCs (Clark et al., 2012). Mice were euthanized directly from the home cage (n = 6) or 1 (n = 7), 3 (n = 7), or 8 h (n = 6) after a 10-min exposure to a NE (Figure 1A). DCX expression was used to identify immature, adult-born neurons. We quantified overall zif268 expression in the general granule cell population as well as co-labeling of DCX with zif268 (Figures 1B,C). NE exposure caused a significant increase in the total number of zif268+ cells in the DG (F(3,22) = 3.961, p = 0.021; Figure 1E). Pairwise comparisons revealed that the total number of zif268+ cells at 1 h post-exposure exceeded the home cage and 8 h levels (p’s ≤ 0.014); the other comparisons did not reach significance.

Bottom Line: The immediate-early gene (IEG) zif268 appears to be an important mediator of these effects, as its expression can be induced by neural activity and knockout of zif268 impairs survival of adult-born neurons (Richardson et al., 1992; Veyrac et al., 2013).In summary, behavioral experience transiently activated expression of zif268 in mature granule cells but caused a more long-lasting suppression of zif268 expression in immature, adult-born granule cells.We hypothesize that zif268 suppression inhibits memory-related synaptic plasticity in immature neurons or mediates learning-induced apoptosis of immature adult-born neurons.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Center for Learning and Memory, University of Texas at Austin Austin, TX, USA.

ABSTRACT
Thousands of neurons are born each day in the dentate gyrus (DG), but many of these cells die before reaching maturity. Both death and survival of adult-born neurons are regulated by neuronal activity in the DG. The immediate-early gene (IEG) zif268 appears to be an important mediator of these effects, as its expression can be induced by neural activity and knockout of zif268 impairs survival of adult-born neurons (Richardson et al., 1992; Veyrac et al., 2013). Despite the apparent importance of zif268 for adult neurogenesis, its behavior-induced expression has not been fully characterized in adult-born neurons. Here we characterize behavior-evoked expression of zif268 in mature and newborn dentate granule cells (DGCs). We first quantified zif268 expression in doublecortin-positive (DCX+) immature neurons and in the general granule cell population after brief exposure to a novel environment (NE). In the general granule cell population, zif268 expression peaked 1 h after NE exposure and returned to baseline by 8 h post-exposure. However, in the DCX+ cells, zif268 expression was suppressed relative to home cage for at least 8 h post-exposure. We next asked whether suppression of zif268 in DCX+ immature cells occurs in other behavioral paradigms that recruit the hippocampus. Exposure to Morris water maze (MWM) training, an enriched environment, or a NE caused approximately equal suppression of zif268 expression in DCX+ cells and approximately equal activation of zif268 expression among the general granule cell population. The same behavioral procedures activated zif268 expression in 6-week-old BrdU-labeled adult-born neurons, indicating that zif268 suppression is specific to immature neurons. Finally, we asked whether zif268 suppression varied as a function of age within the DCX+ population, which ranges in age from 0 to approximately 4 weeks. NE exposure had no significant effect on zif268 expression in 2- or 4-week-old BrdU-labeled neurons, but it significantly suppressed zif268 expression in 3-week-old neurons. In summary, behavioral experience transiently activated expression of zif268 in mature granule cells but caused a more long-lasting suppression of zif268 expression in immature, adult-born granule cells. We hypothesize that zif268 suppression inhibits memory-related synaptic plasticity in immature neurons or mediates learning-induced apoptosis of immature adult-born neurons.

No MeSH data available.


Related in: MedlinePlus