ReviewEffects of environmental enrichment and voluntary exercise on neurogenesis, learning and memory, and pattern separation: BDNF as a critical variable?
Highlights
► Environmental enrichment is associated with increased learning and memory. ► Voluntary exercise is associated with increased learning and memory. ► Environmental enrichment and voluntary exercise increase neurogenesis and BDNF. ► Both neurogenesis and BDNF are required for pattern separation. ► BDNF might be a third variable responsible for learning and memory enhancement.
Section snippets
Effects of environmental enrichment and physical exercise on neurogenesis and learning and memory
The adult brain produces new neurons in substantial numbers, a phenomenon that has been firmly established since its initial discovery [1], [2]. Of particular interest to researchers interested in the neurobiology of L&M are the newborn granule neurons in the hippocampus. These cells functionally integrate into the hippocampal dentate gyrus (DG) network [3], and receive synaptic input from the entorhinal cortex and form functional terminals onto CA3 cells [4], [5]. In addition, adult-born
Correlation, causation, and the problem of the third variable
As discussed previously, there is much evidence to demonstrate that both EE and Vex can increase NG in the adult hippocampus. However, whether the beneficial effects of EE and Vex on L&M are caused directly by NG, remains unclear. One obvious problem is that correlation does not imply causation. One alternative interpretation of the finding that NG correlates with EE or Vex is that, rather than increases in NG being causally related to improvements in L&M, there may be a “third variable” caused
Brain-derived neurotrophic factor (BDNF) as a possible third variable
Several lines of evidence provide a link between BDNF and L&M. First, BDNF has been found to play an important role in the late phase of long-term potentiation (LTP), the best known cellular plasticity phenomenon in the brain [36], [37], [38], which is thought to be one of the plastic phenomena that underlie L&M [39], [40]. For example, Pang and others have shown that BDNF is necessary for the late phase of LTP (L-LTP) in the CA1 region of the hippocampus [41]. Second, BDNF mRNA and protein
Concluding remarks
To summarise, we have suggested that in experiments investigating the link between EE, Vex, NG and L&M, there could exist a third variable, brought about by EE and/or Vex, acting as a causal determinant of both NG and L&M, and that this third variable could be a neurotrophic and/or plasticity-related factor such as BDNF. Of course this suggestion could be wrong; further appropriate experiments testing EE/Vex with NG knock-down and L&M (ideally examining pattern separation) may well generate
Acknowledgments
The authors would like to thank Dr. Henriette van Praag for helpful discussion of the manuscript. This work was funded by a grant from the BBSRC (TJB, LMS and PB). CAO is supported by a grant from Janssen Pharmaceuticals.
References (112)
- et al.
A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain
Neuron
(2007) - et al.
Computational influence of adult neurogenesis on memory encoding
Neuron
(2009) - et al.
Neurogenesis in adulthood: a possible role in learning
Trends Cogn Sci
(1999) - et al.
Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: implications for depression and antidepressant action
Eur Neuropsychopharmacol
(2010) - et al.
Effects of environmental enrichment on cortical depth and Morris-maze performance in B6D2F2 mice exposed prenatally to ethanol
Neurotoxicol Teratol
(1993) - et al.
Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment
Neurosci Lett
(1992) - et al.
Modeling brain reserve: experience-dependent neuronal plasticity in healthy and Huntington's disease transgenic mice
Am J Geriatr Psychiatry
(2009) - et al.
Intact neurogenesis is required for benefits of exercise on spatial memory but not motor performance or contextual fear conditioning in C57BL/6J mice
Neuroscience
(2008) - et al.
Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory
Cell
(2009) LTP forms 1, 2 and 3: different mechanisms for the “long” in long-term potentiation
Trends Neurosci
(2007)
Local protein synthesis, actin dynamics, and LTP consolidation
Curr Opin Neurobiol
Brain-derived neurotrophic factor/TrkB signaling in memory processes
J Pharmacol Sci
Persistence of long-term memory storage requires a late protein synthesis- and BDNF-dependent phase in the hippocampus
Neuron
BDNF overexpression increases dendrite complexity in hippocampal dentate gyrus
Neuroscience
Essential role for TrkB receptors in hippocampus-mediated learning
Neuron
Memory consolidation in day-old chicks requires BDNF but not NGF or NT-3; an antisense study
Brain Res Mol Brain Res
Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat
Neuroscience
A role for adult neurogenesis in spatial long-term memory
Neuroscience
Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice
Exp Neurol
Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain
Brain Res
Interplay between brain-derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity
Neuroscience
Long-term environmental enrichment leads to regional increases in neurotrophin levels in rat brain
Exp Neurol
Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo
Neuroscience
Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism
Neuron
Increased neurogenesis and the ectopic granule cells after intrahippocampal BDNF infusion in adult rats
Exp Neurol
Cell death in regenerating populations of neurons in BDNF mutant mice
Brain Res Mol Brain Res
TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment
Neuron
Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats
J Comp Neurol
Adult neurogenesis
Stem cells and neuronal development in the adult brain
Functional neurogenesis in the adult hippocampus
Nature
Neurons born in the adult dentate gyrus form functional synapses with target cells
Nat Neurosci
Synapse formation on neurons born in the adult hippocampus
Nat Neurosci
Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus
Nature
A functional hypothesis for adult hippocampal neurogenesis: avoidance of catastrophic interference in the dentate gyrus
Hippocampus
New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?
Nat Rev Neurosci
Is there a link between adult neurogenesis and learning?
Hippocampus
Adult neurogenesis: from precursors to network and physiology
Physiol Rev
More hippocampal neurons in adult mice living in an enriched environment
Nature
Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus
Nat Neurosci
Exercise improves memory acquisition and retrieval in the Y-maze task: relationship with hippocampal neurogenesis
Behav Neurosci
Running enhances neurogenesis, learning, and long-term potentiation in mice
Proc Natl Acad Sci USA
Exercise enhances learning and hippocampal neurogenesis in aged mice
J Neurosci
Enriched environment increases neurogenesis in the adult rat dentate gyrus and improves spatial memory
J Neurobiol
Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment
Ann Neurol
Effects of differential environments on brain weights and enzyme activities in gerbils, rats, and mice
Dev Psychobiol
Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice
Nat Neurosci
Relatively brief environmental enrichment aids recovery of learning capacity and alters brain measures after postweaning brain lesions in rats
J Comp Physiol Psychol
Short-term environmental enrichment enhances adult neurogenesis, vascular network and dendritic complexity in the hippocampus of type 1 diabetic mice
PLoS ONE
Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment
Nat Neurosci
New neurons in the dentate gyrus are involved in the expression of enhanced long-term memory following environmental enrichment
Eur J Neurosci
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