A new perspective of the hippocampus in the origin of exercise–brain interactions
Exercising regularly is a highly effective strategy for maintaining cognitive health throughout the lifespan. Over the last 20 years, many molecular, physiological and structural changes have been documented in response to aerobic exercise training in humans and animals, particularly in the hippocampus. However, how exercise produces such neurological changes remains elusive. A recent line of investigation has suggested that muscle-derived circulating factors cross into the brain and may be the key agents driving enhancement in synaptic plasticity and hippocampal neurogenesis from aerobic exercise. Alternatively, or concurrently, the signals might originate from within the brain itself. Physical activity also produces instantaneous and robust neuronal activation of the hippocampal formation and the generation of theta oscillations which are closely correlated with the force of movements. The repeated acute activation of the hippocampus during physical movement is likely critical for inducing the long-term neuroadaptations from exercise. Here we review the evidence which establishes the association between physical movement and hippocampal neuronal activation and discuss implications for long-term benefits of physical activity on brain function.
KeywordsExercise Hippocampus Theta rhythm Learning Memory Physical activity Neurogenesis Movement Spatial learning Plasticity Neuronal activation Muscle Myokines
The authors acknowledge Dr. João Guerreiro for his contribution in preparing Fig. 2.
This work was supported by NIH R21 NS104293, R01 MH083807 and R01 DA027487.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants and/or animals
Not applicable, no original studies were conducted, this is a review article.
- Agudelo LZ, Femenia T, Orhan F, Porsmyr-Palmertz M, Goiny M, Martinez-Redondo V, Correia JC, Izadi M, Bhat M, Schuppe-Koistinen I, Pettersson AT, Ferreira DM, Krook A, Barres R, Zierath JR, Erhardt S, Lindskog M, Ruas JL (2014) Skeletal muscle PGC-1alpha1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. Cell 159(1):33–45PubMedCrossRefGoogle Scholar
- Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Hojlund K, Gygi SP, Spiegelman BM (2012) A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481(7382):463–468PubMedPubMedCentralCrossRefGoogle Scholar
- Eaton M, Granatab C, Barrya J, Safdarc A, Bishopb D, Jonathan P, Littlea (2017) Impact of a single bout of high-intensity interval exercise and short-term interval training on interleukin-6, FNDC5, and METRNL mRNA expression in human skeletal muscle. J Sport Health Sci 1–6. https://doi.org/10.1016/j.jshs.2017.01.003
- Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF (2011) Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci USA 108(7):3017–3022PubMedPubMedCentralCrossRefGoogle Scholar
- Fuhrmann F, Justus D, Sosulina L, Kaneko H, Beutel T, Friedrichs D, Schoch S, Schwarz MK, Fuhrmann M, Remy S (2015) Locomotion, theta oscillations, and the speed-correlated firing of hippocampal neurons are controlled by a medial septal glutamatergic circuit. Neuron 86(5):1253–1264PubMedCrossRefGoogle Scholar
- Hebb DO (1949) The organisation of behavior. Wiley, New YorkGoogle Scholar
- Morris R, Hagen J (1983) Hippocampal electrical activity and ballistic movement. Neurobiology of the hippocampus. Academic Press, LondonGoogle Scholar
- Neufer PD, Bamman MM, Muoio DM, Bouchard C, Cooper DM, Goodpaster BH, Booth FW, Kohrt WM, Gerszten RE, Mattson MP, Hepple RT, Kraus WE, Reid MB, Bodine SC, Jakicic JM, Fleg JL, Williams JP, Joseph L, Evans M, Maruvada P, Rodgers M, Roary M, Boyce AT, Drugan JK, Koenig JI, Ingraham RH, Krotoski D, Garcia-Cazarin M, McGowan JA, Laughlin MR (2015) Understanding the cellular and molecular mechanisms of physical activity-induced health benefits. Cell Metab 22(1):4–11PubMedCrossRefGoogle Scholar
- Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, Smith LK, Bieri G, Lin K, Berdnik D, Wabl R, Udeochu J, Wheatley EG, Zou B, Simmons DA, Xie XS, Longo FM, Wyss-Coray T (2014) Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med 20(6):659–663PubMedPubMedCentralCrossRefGoogle Scholar