Environmental enrichment improves learning and memory and long-term potentiation in young adult rats through a mechanism requiring mGluR5 signaling and sustained activation of p70s6k.
Previous studies from our lab have demonstrated that mild cognitive impairments identified early in life are predictive of cognitive deficits that develop with age, suggesting that enhancements in cognition at an early age can provide a buffer against age-related cognitive decline. Environmental enrichment has been shown to improve learning and memory in the rodent, but the impact of enrichment on synaptic plasticity and the molecular mechanisms behind enrichment are not completely understood. To address these unresolved issues, we have housed 2-month old rats in environmentally enriched (EE), socially enriched (SE), or standard housing (SC) and conducted tests of learning and memory formation at various time intervals. Here we demonstrate that animals that have been exposed to one month of social or environmental enrichment demonstrate enhanced learning and memory relative to standard housed controls. However, we have found that after 4months EE animals perform better than both SE and SC groups and demonstrate an enhanced hippocampal LTP. Our results demonstrate that this LTP is dependent on mGluR5 signaling, activation of ERK and mTOR signaling cascades, and sustained phosphorylation of p70s6 kinase, thus providing a potential target mechanism for future studies of cognitive enhancement in the rodent.
Neuroscience Training Program, University of Wisconsin-Madison, USA.
Rikki
R
Hullinger
Department of Pharmacology & Therapeutics, Biotechnology (Watts) Building, Trinity College, Dublin 2, Ireland(1).
Kenneth
K
O'Riordan
Department of Neurology, University of Wisconsin-Madison, Medical Sciences Center, 1300 University Ave, Room 73 Bardeen, Madison, WI 53706, USA; Neuroscience Training Program, University of Wisconsin-Madison, USA. Electronic address: burger@neurology.wisc.edu.
Corinna
C
Burger
D000818:Animals; D004777:Environment; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006799:Housing, Animal; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; C121465:6-methyl-2-(phenylethynyl)pyridine; D038762:Ribosomal Protein S6 Kinases, 70-kDa
Environmental enrichment; Metabotropic glutamate receptor; Morris water maze; Object recognition; Young rats; p70s6 kinase