Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo
Abstract
We have previously shown that voluntary exercise produces enhanced neurogenesis and long-term potentiation (LTP) in the dentate gyrus (DG) of mice in vitro. In the present experiments we show that rats given access to a running wheel (Runners) exhibit significantly more short-term potentiation and LTP with theta-patterned conditioning stimulation in vivo than do age-matched litter mates (Controls). This increase in LTP appears to reflect an alteration in the induction threshold for synaptic plasticity that accompanies voluntary exercise. Weak theta-patterned stimulation, which did not produce LTP in control subjects, produced a robust and long-lasting LTP in Runners. LTP induction in both groups was dependent upon the activation of N-methyl-D-aspartate (NMDA) receptors, and could be blocked by the competitive antagonist [+/-]-3-[2-carboxypiperazin-4-yl] propanephosphonic acid. Consistent with these findings, we found that mRNA levels for NR2B subtype of NMDA receptor were increased specifically in the DG of Runners. In addition to changes in NR2B mRNA levels, quantitative polymerase chain reaction analysis revealed that brain-derived neurotrophic factor (BDNF) and glutamate receptor 5 mRNA levels were also significantly elevated in the DG of Runners, but not in other areas of the hippocampus. Thus, alterations in the expression of BDNF, and specific glutamate receptor subtypes, may underlie the ability of exercise to enhance neurogenesis and reduce the threshold for LTP in the DG.
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Rodent studies demonstrate increased BDNF mRNA and BDNF protein within the hippocampus in response to wheel running for 1-8 weeks.
“Rodent studies demonstrate increased BDNF mRNA and BDNF protein within the hippocampus in response to wheel running for 1-8 weeks (87-92).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [91]
Aerobic exercise interacts with the glutamatergic system through increasing the expression of NMDA receptors in the hippocampus (NR2A and NR2B subtypes), which contributes toward synaptic plasticity.
“AE also interacts with the glutamatergic system through increasing the expression of N-methyl-D-aspartic acid (NMDA) receptors in the hippocampus (specifically, both NR2A and NR2B subtypes), which contributes toward the synaptic plasticity of the region (Molteni et al., 2002; Farmer et al., 2004).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Farmer et al., 2004
Rodents that run voluntarily on running wheels exhibit increased numbers of dendritic spines and synapses in hippocampal neurons, increased neurogenesis, and improved performance in some behavioral tests of cognitive function.
“Rodents that run voluntarily on running wheels exhibit increased numbers of dendritic spines and synapses in hippocampal neurons, increased neurogenesis, and improved performance in some behavioral tests of cognitive function [59, 185].”
From The neuropathology of sport (2014) · cites this paper as [59]
Physical activity, cognitive stimulation, and a balanced diet can stimulate BDNF expression in humans and animals.
“Several studies on both humans and animals show that physical activity, cognitive stimulation, and a balanced diet can stimulate BDNF expression [204–207].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [207]
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“AE also interacts with the glutamatergic system through increasing the expression of N -methyl- D -aspartic acid (NMDA) receptors in the hippocampus (specifically, both NR2A and NR2B subtypes), which contributes toward the synaptic plasticity of the region (Molteni et al., 2002; Farmer et al., 2004).”
An umbrella review of randomized control trials on the effects of physical exercise on cognition
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- Authors
- Farmer, J., Zhao, X., van Praag, H., Wodtke, K., Gage, F. H., & Christie, B. R.
- Affiliations
- University of British Columbia (CA)
- Salk Institute for Biological Studies (US)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2004-01
- Volume
- 124
- Issue
- 1
- Pages
- 71-79
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2122586715
- Cited by
- 836
- References
- 76
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 18 · 2023: 30 · 2022: 29 · 2021: 27 · 2020: 33 · 2019: 41 · 2018: 40 · 2017: 48 · 2016: 52 · 2015: 52 · 2014: 39 · 2013: 49 · 2012: 49
- FWCI
- 13.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (F32NS010826)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- voluntary exercise, running wheel, synaptic plasticity, long-term potentiation, short-term potentiation, dentate gyrus, NMDA receptor, brain-derived neurotrophic factor, gene expression, hippocampus, Sprague-Dawley rats
- MeSH terms
- Age Factors, Animals, Cell Count, Cell Division, Electric Stimulation, Male, Neuronal Plasticity, Neurons, Physical Conditioning, Animal, RNA, Messenger, Running, Volition, Gene Expression, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Long-Term Potentiation, Kainic Acid Receptors, Dentate Gyrus, Brain-Derived Neurotrophic Factor, Rats
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