Temporal spacing of synaptic stimulation critically modulates the dependence of LTP on cyclic AMP-dependent protein kinase

Newton H Woo; Steven N Duffy; Ted Abel; Peter V Nguyen

doi:10.1002/hipo.10086

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Journal article

Temporal spacing of synaptic stimulation critically modulates the dependence of LTP on cyclic AMP-dependent protein kinase

Newton H Woo, Steven N Duffy, Ted Abel and Peter V Nguyen

Hippocampus, Vol.13(2), pp.293-300

2003

DOI: 10.1002/hipo.10086

PMID: 12699336

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Abstract

Genetic and electrophysiological experiments have defined an important role for cAMP-dependent protein kinase (PKA) in certain forms of long-term potentiation (LTP). However, the characteristics of stimulation that are critical for regulating the PKA-dependence of LTP have not been clearly defined. In the present study, we have used PKA mutant mice (R(AB) transgenic mice), which have reduced PKA activity in neurons within the hippocampus, to explore the role of temporal spacing of synaptic stimulation in regulating the PKA-dependence of LTP. The time interval between successive bursts of electrical stimulation was varied while keeping constant the total number of stimulus pulses. LTP induced by temporally spaced tetraburst synaptic stimulation was impaired in the Schaeffer collateral pathway of hippocampal slices from R(AB) mutant mice. In contrast, LTP induced by temporally compressed tetraburst stimulation was normal in slices from R(AB) mutants, and its long-term maintenance was not significantly affected by bath application of KT-5720, an inhibitor of catalytic subunits of PKA. In slices from wildtype mice, LTP induced by spaced tetraburst stimulation was significantly attenuated by KT-5720. These genetic and pharmacological experiments show that LTP induced by these compressed patterns of stimulation does not require PKA activation. Thus, altering the temporal spacing of synaptic stimulation per se critically modulates the PKA-dependence of hippocampal LTP. PKA-dependent LTP is selectively recruited by temporally spaced, multiburst synaptic stimulation.

Receptors, N-Methyl-D-Aspartate - drug effects

Electric Stimulation

Synapses - physiology

Electrophysiology

Male

Mice, Transgenic

Receptors, N-Methyl-D-Aspartate - physiology

Excitatory Postsynaptic Potentials - physiology

Cyclic AMP-Dependent Protein Kinases - physiology

Animals

Long-Term Potentiation - physiology

Female

Mice

In Vitro Techniques

Details

Title: Subtitle: Temporal spacing of synaptic stimulation critically modulates the dependence of LTP on cyclic AMP-dependent protein kinase
Creators: Newton H Woo - Department of Physiology, University of Alberta School of Medicine, Edmonton, Alberta, Canada
Steven N Duffy
Ted Abel
Peter V Nguyen
Resource Type: Journal article
Publication Details: Hippocampus, Vol.13(2), pp.293-300
DOI: 10.1002/hipo.10086
PMID: 12699336
NLM abbreviation: Hippocampus
ISSN: 1050-9631
eISSN: 1098-1063
Publisher: United States
Grant note: HD26979 / NICHD NIH HHS AG18199 / NIA NIH HHS MH60244 / NIMH NIH HHS
Language: English
Date published: 2003
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065821802771

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