New neurons generated from running are broadly recruited into neuronal activation associated with three different hippocampus-involved tasks - PubMed (original) (raw)

New neurons generated from running are broadly recruited into neuronal activation associated with three different hippocampus-involved tasks

Peter J Clark et al. Hippocampus. 2012 Sep.

Abstract

Running increases the formation of new neurons in the adult rodent hippocampus. However, the function of new neurons generated from running is currently unknown. One hypothesis is that new neurons from running contribute to enhanced cognitive function by increasing plasticity in the adult hippocampus. An alternative hypothesis is that new neurons generated from running incorporate into experience-specific hippocampal networks that only become active during running. The purpose of this experiment was to determine if new neurons generated from running are selectively activated by running, or can become recruited into granule cell activity occurring during performance on other behavioral tasks that engage the hippocampus. Therefore, the activation of new 5-6 week neurons was detected using BrdU, NeuN, and Zif268 triple-label immunohistochemistry in cohorts of female running and sedentary adult C57BL/6J mice following participation in one of three different tasks: the Morris water maze, novel environment exploration, or wheel running. Results showed that running and sedentary mice displayed a nearly equivalent proportion of new neurons that expressed Zif268 following each task. Since running approximately doubled the number of new neurons, the results demonstrated that running mice had a greater number of new neurons recruited into the Zif268 induction in the granule cell layer following each task than sedentary mice. The results suggest that new neurons incorporated into hippocampal circuitry from running are not just activated by wheel running itself, but rather become broadly recruited into granule cell layer activity during distinct behavioral experiences.

Copyright © 2012 Wiley Periodicals, Inc.

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Figures

Figure 1

Figure 1

Experimental design. Mice were housed with or without running wheels for 30 days. The first 10 days the mice received daily injections of 50 mg/kg BrdU to label dividing cells. Behavioral tasks began during the final 12 days, days 31–42. All mice were housed in cages without access to running wheels on days 31–42 and throughout behavioral testing, except the Run/Sed and Run/Run groups (see below). Mice in the caged control group were continuously housed in custom cages (for video tracking) on days 31–42. The novel group received a single 2h exposure to the custom cages on day 42. The water maze group received 3 days (2 trials/day for 2 days, 3 trials on the 3rd day) of hidden platform water maze training. The yoked swim group received exposure to the water maze without a platform and served as a swim control for the water maze group. The run groups (Run/Sed and Run/Run) were continuously housed in cages with access to running wheels on days 37–42. All mice were euthanized on day 42, two hours following behavioral testing to measure Zif268 induction.

Figure 2

Figure 2

Zif268 induction in the granule cell layer from each task. A) Representative coronal section of a mouse from the caged control group containing the granule cell layer stained for Zif268 using DAB as the chromogen with a light Nissl stain to highlight the dentate gyrus. B) same as A) except containing representative section of a mouse that was running 2hr before euthanasia. C) Average number of Zif268 labeled cells (± SE) per cubic mm in the granule layer of sedentary and running mice in caged control and novel environment groups. D) same as C) except containing the yoked swim and water maze groups. E) Same as C) except containing the wheel running group. aP<0.0001 from caged control. bP<0.05 from yoked swim.

Figure 3

Figure 3

New neurons from running are broadly recruited into Zif268 induction during different behavioral tasks. A) Representative coronal section of the dentate gyrus stained for BrdU (green), NeuN (blue), and Zif268 (red) containing a region in the white box with arrows pointing at two zoomed in triple-labeled neurons. B) Percentage of BrdU−/NeuN+ and BrdU+/NeuN+ neurons that displayed Zif268 (± SE) in running and sedentary mice during performance on each behavioral task. C) Average density of Zif268 expression in the granule cell layer for each behavioral task plotted against the percentage of new neurons that displayed Zif268. Note that each point represents the mean values of multiple mice for each behavioral task, plotted separately for running and sedentary mice. D) Estimated number of BrdU+/NeuN+ cells (± SE) in running and sedentary mice aP<0.01 from BrdU− in each group, aaP<0.0001 from sedentary

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