Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Persistent protein kinase activity underlying long-term potentiation.

R Malinow1, D V Madison, R W Tsien

  • 1Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510.

Nature
|October 27, 1988
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Cntnap4 differentially contributes to GABAergic and dopaminergic synaptic transmission.

Nature·2014
Same author

A transition state theory approach to the kinetics of conductance changes in excitable membranes.

The Journal of membrane biology·2013
Same author

Preparation of hippocampal brain slices.

Current protocols in neuroscience·2008
Same author

AMPA receptor phosphorylation during synaptic plasticity.

Biochemical Society transactions·2005
Same author

Differential expression of alpha 1 and beta subunits of voltage dependent Ca2+ channel at the neuromuscular junction of normal and P/Q Ca2+ channel knockout mouse.

Neuroscience·2003
Same author

Imaging single synaptic vesicles undergoing repeated fusion events: kissing, running, and kissing again.

Neuropharmacology·2003

Long-term potentiation (LTP) is sustained by persistent protein kinase activity, not a stable substrate. This kinase activity is constitutive and remains active even when blocked, suggesting a novel mechanism for synaptic enhancement.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Synaptic Plasticity

Background:

  • Long-term potentiation (LTP) in the hippocampus is a key model for synaptic plasticity.
  • N-methyl-D-aspartate (NMDA) receptors are crucial for LTP induction, but the persistent signal maintaining LTP is unknown.
  • Protein phosphorylation by kinases like PKC and CaMKII is hypothesized to underlie LTP.

Purpose of the Study:

  • To investigate the molecular nature of the persistent signal sustaining hippocampal LTP.
  • To differentiate between a stably phosphorylated substrate, a long-lived kinase activator, or a constitutively active kinase.

Main Methods:

  • Utilized H-7, an inhibitor of activated protein kinases.
  • Employed sphingosine, a competitive inhibitor of PKC and CaMKII activators.

Related Experiment Videos

  • Administered inhibitors before and after tetanic stimulation to induce LTP.

    • Main Results:

    • H-7 suppressed established LTP, indicating ongoing protein kinase activity is necessary for maintenance.
    • Sphingosine did not affect established LTP, but inhibited induction when applied beforehand.
    • The inhibitory effect of H-7 on LTP was reversible, and LTP was not sustained by autophosphorylation.

    Conclusions:

    • Hippocampal LTP is maintained by persistent, constitutively active protein kinase activity, not a permanently phosphorylated substrate.
    • The underlying kinase remains in an active state even when its catalytic function is temporarily inhibited.
    • This suggests a unique mechanism for sustained synaptic enhancement independent of continuous activation or autophosphorylation.