Environmental Enrichment Modifies the PKA-Dependence of Hippocampal LTP and Improves Hippocampus-Dependent Memory
Open Access
- 1 January 2001
- journal article
- Published by Cold Spring Harbor Laboratory in Learning & Memory
- Vol. 8 (1), 26-34
- https://doi.org/10.1101/lm.36301
Abstract
CAMP-dependent protein kinase (PKA) is critical for the expression of some forms of long-term potentiation (LTP) in area CA1 of the mouse hippocampus and for hippocampus-dependent memory. Exposure to spatially enriched environments can modify LTP and improve behavioral memory in rodents, but the molecular bases for the enhanced memory performance seen in enriched animals are undefined. We tested the hypothesis that exposure to a spatially enriched environment may alter the PKA dependence of hippocampal LTP. Hippocampal slices from enriched mice showed enhanced LTP following a single burst of 100-Hz stimulation in the Schaffer collateral pathway of area CA1. In slices from nonenriched mice, this single-burst form of LTP was less robust and was unaffected by Rp-cAMPS, an inhibitor of PKA. In contrast, the enhanced LTP in enriched mice was attenuated by Rp-cAMPS. Enriched slices expressed greater forskolin-induced, cAMP-dependent synaptic facilitation than did slices from nonenriched mice. Enriched mice showed improved memory for contextual fear conditioning, whereas memory for cued fear conditioning was unaffected following enrichment. Our data indicate that exposure of mice to spatial enrichment alters the PKA dependence of LTP and enhances one type of hippocampus-dependent memory. Environmental enrichment can transform the pharmacological profile of hippocampal LTP, possibly by altering the threshold for activity-dependent recruitment of the cAMP-PKA signaling pathway following electrical and chemical stimulation. We suggest that experience-dependent plasticity of the PKA dependence of hippocampal LTP may be important for regulating the efficacy of hippocampus-based memory.Keywords
This publication has 70 references indexed in Scilit:
- (RP)‐cAMPS inhibits the cAMP‐dependent protein kinase by blocking the cAMP‐induced conformational transitionFEBS Letters, 1995
- Effects of environmental enrichment on aggressive behavior, dominance hierarchies, and endocrine states in male DBA/2J micePhysiology & Behavior, 1994
- Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.Behavioral Neuroscience, 1992
- Postsynaptic Calcium Is Sufficient for Potentiation of Hippocampal Synaptic TransmissionScience, 1988
- Behavioral stress impairs long-term potentiation in rodent hippocampusBehavioral and Neural Biology, 1987
- K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinasesBiochemical and Biophysical Research Communications, 1986
- Alkylxanthines: Inhibition of adenosine-elicited accumulation of cyclic AMP in brain slices and of brain phosphodiesterase activityLife Sciences, 1979
- Physiological and morphological identification of a nonpyramidal hippocampal cell typeBrain Research, 1978
- Ferrier lecture - Functional architecture of macaque monkey visual cortexProceedings of the Royal Society of London. B. Biological Sciences, 1977
- Appetitive and aversive conditioning in thiamine-deficient rats.Journal of Comparative and Physiological Psychology, 1973