Intermediate-Term Memory for Site-Specific Sensitization in Aplysia is Maintained by Persistent Activation of Protein Kinase C

Michael A. Sutton, Martha W. Bagnall, Shiv K. Sharma, Justin Shobe, Thomas Carew

Research output: Contribution to journalArticle

Abstract

Recent studies of long-term synaptic plasticity and long-term memory have demonstrated that the same functional endpoint, such as long-term potentiation, can be induced through distinct signaling pathways engaged by different patterns of stimulation. A critical question raised by these studies is whether different induction pathways either converge onto a common molecular mechanism or engage different molecular cascades for the maintenance of long-term plasticity. We directly examined this issue in the context of memory for sensitization in the marine mollusk Aplysia. In this system, training with a single tail shock normally induces short-term memory (< 30 min) for sensitization of tail-elicited siphon withdrawal, whereas repeated spaced shocks induce both intermediate-term memory (ITM) (>90 min) and long-term memory (>24 hr). We now show that a single tail shock can also induce ITM that is expressed selectively at the trained site (site-specific ITM). Although phenotypically similar to the form of ITM induced by repeated trials, the mechanisms by which site-specific ITM is induced and maintained are distinct. Unlike repeated-trial ITM, site-specific ITM requires neither protein synthesis nor PKA activity for induction or maintenance. Rather, the induction of site-specific ITM requires calpain-dependent proteolysis of activated PKC, yielding a persistently active PKC catalytic fragment (PKM) that also serves to maintain the memory in the intermediate-term temporal domain. Thus, two unique forms of ITM that have different induction requirements also use distinct molecular mechanisms for their maintenance.

Original languageEnglish (US)
Pages (from-to)3600-3609
Number of pages10
JournalJournal of Neuroscience
Volume24
Issue number14
DOIs
StatePublished - Apr 7 2004

Fingerprint

Aplysia
Long-Term Memory
Protein Kinase C
Tail
Shock
Maintenance
Neuronal Plasticity
Calpain
Long-Term Potentiation
Mollusca
Short-Term Memory
Proteolysis
Proteins

Keywords

  • Calpain
  • Learning
  • PKA
  • PKM
  • Protein synthesis
  • Proteolysis
  • Synaptic facilitation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Intermediate-Term Memory for Site-Specific Sensitization in Aplysia is Maintained by Persistent Activation of Protein Kinase C. / Sutton, Michael A.; Bagnall, Martha W.; Sharma, Shiv K.; Shobe, Justin; Carew, Thomas.

In: Journal of Neuroscience, Vol. 24, No. 14, 07.04.2004, p. 3600-3609.

Research output: Contribution to journalArticle

Sutton, Michael A. ; Bagnall, Martha W. ; Sharma, Shiv K. ; Shobe, Justin ; Carew, Thomas. / Intermediate-Term Memory for Site-Specific Sensitization in Aplysia is Maintained by Persistent Activation of Protein Kinase C. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 14. pp. 3600-3609.
@article{b05689a12ca742faa73e5ad54f1f81c4,
title = "Intermediate-Term Memory for Site-Specific Sensitization in Aplysia is Maintained by Persistent Activation of Protein Kinase C",
abstract = "Recent studies of long-term synaptic plasticity and long-term memory have demonstrated that the same functional endpoint, such as long-term potentiation, can be induced through distinct signaling pathways engaged by different patterns of stimulation. A critical question raised by these studies is whether different induction pathways either converge onto a common molecular mechanism or engage different molecular cascades for the maintenance of long-term plasticity. We directly examined this issue in the context of memory for sensitization in the marine mollusk Aplysia. In this system, training with a single tail shock normally induces short-term memory (< 30 min) for sensitization of tail-elicited siphon withdrawal, whereas repeated spaced shocks induce both intermediate-term memory (ITM) (>90 min) and long-term memory (>24 hr). We now show that a single tail shock can also induce ITM that is expressed selectively at the trained site (site-specific ITM). Although phenotypically similar to the form of ITM induced by repeated trials, the mechanisms by which site-specific ITM is induced and maintained are distinct. Unlike repeated-trial ITM, site-specific ITM requires neither protein synthesis nor PKA activity for induction or maintenance. Rather, the induction of site-specific ITM requires calpain-dependent proteolysis of activated PKC, yielding a persistently active PKC catalytic fragment (PKM) that also serves to maintain the memory in the intermediate-term temporal domain. Thus, two unique forms of ITM that have different induction requirements also use distinct molecular mechanisms for their maintenance.",
keywords = "Calpain, Learning, PKA, PKM, Protein synthesis, Proteolysis, Synaptic facilitation",
author = "Sutton, {Michael A.} and Bagnall, {Martha W.} and Sharma, {Shiv K.} and Justin Shobe and Thomas Carew",
year = "2004",
month = "4",
day = "7",
doi = "10.1523/JNEUROSCI.1134-03.2004",
language = "English (US)",
volume = "24",
pages = "3600--3609",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "14",

}

TY - JOUR

T1 - Intermediate-Term Memory for Site-Specific Sensitization in Aplysia is Maintained by Persistent Activation of Protein Kinase C

AU - Sutton, Michael A.

AU - Bagnall, Martha W.

AU - Sharma, Shiv K.

AU - Shobe, Justin

AU - Carew, Thomas

PY - 2004/4/7

Y1 - 2004/4/7

N2 - Recent studies of long-term synaptic plasticity and long-term memory have demonstrated that the same functional endpoint, such as long-term potentiation, can be induced through distinct signaling pathways engaged by different patterns of stimulation. A critical question raised by these studies is whether different induction pathways either converge onto a common molecular mechanism or engage different molecular cascades for the maintenance of long-term plasticity. We directly examined this issue in the context of memory for sensitization in the marine mollusk Aplysia. In this system, training with a single tail shock normally induces short-term memory (< 30 min) for sensitization of tail-elicited siphon withdrawal, whereas repeated spaced shocks induce both intermediate-term memory (ITM) (>90 min) and long-term memory (>24 hr). We now show that a single tail shock can also induce ITM that is expressed selectively at the trained site (site-specific ITM). Although phenotypically similar to the form of ITM induced by repeated trials, the mechanisms by which site-specific ITM is induced and maintained are distinct. Unlike repeated-trial ITM, site-specific ITM requires neither protein synthesis nor PKA activity for induction or maintenance. Rather, the induction of site-specific ITM requires calpain-dependent proteolysis of activated PKC, yielding a persistently active PKC catalytic fragment (PKM) that also serves to maintain the memory in the intermediate-term temporal domain. Thus, two unique forms of ITM that have different induction requirements also use distinct molecular mechanisms for their maintenance.

AB - Recent studies of long-term synaptic plasticity and long-term memory have demonstrated that the same functional endpoint, such as long-term potentiation, can be induced through distinct signaling pathways engaged by different patterns of stimulation. A critical question raised by these studies is whether different induction pathways either converge onto a common molecular mechanism or engage different molecular cascades for the maintenance of long-term plasticity. We directly examined this issue in the context of memory for sensitization in the marine mollusk Aplysia. In this system, training with a single tail shock normally induces short-term memory (< 30 min) for sensitization of tail-elicited siphon withdrawal, whereas repeated spaced shocks induce both intermediate-term memory (ITM) (>90 min) and long-term memory (>24 hr). We now show that a single tail shock can also induce ITM that is expressed selectively at the trained site (site-specific ITM). Although phenotypically similar to the form of ITM induced by repeated trials, the mechanisms by which site-specific ITM is induced and maintained are distinct. Unlike repeated-trial ITM, site-specific ITM requires neither protein synthesis nor PKA activity for induction or maintenance. Rather, the induction of site-specific ITM requires calpain-dependent proteolysis of activated PKC, yielding a persistently active PKC catalytic fragment (PKM) that also serves to maintain the memory in the intermediate-term temporal domain. Thus, two unique forms of ITM that have different induction requirements also use distinct molecular mechanisms for their maintenance.

KW - Calpain

KW - Learning

KW - PKA

KW - PKM

KW - Protein synthesis

KW - Proteolysis

KW - Synaptic facilitation

UR - http://www.scopus.com/inward/record.url?scp=1842631465&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1842631465&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.1134-03.2004

DO - 10.1523/JNEUROSCI.1134-03.2004

M3 - Article

VL - 24

SP - 3600

EP - 3609

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 14

ER -