PKMζ inhibition disrupts reconsolidation and erases object recognition memory

Object recognition memory (ORM) confers the ability to discriminate the familiarity of previously encountered items. Reconsolidation is the process by which reactivated memories become labile and susceptible to modifications. The hippocampus is specifically engaged in reconsolidation to integrate ne...

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Principais autores: Rossato, Janine I., Gonzalez, Maria Carolina, Radiske, Andressa, Apolinário, Gênedy, Conde-Ocazionez, Sergio, Bevilaqua, Lia Rejane Müller, Cammarota, Martín Pablo
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Idioma:English
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PKMζ
memory
reconsolidation
Endereço do item:https://repositorio.ufrn.br/jspui/handle/123456789/26760
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spelling ri-123456789-267602021-07-09T21:06:52Z PKMζ inhibition disrupts reconsolidation and erases object recognition memory Rossato, Janine I. Gonzalez, Maria Carolina Radiske, Andressa Apolinário, Gênedy Conde-Ocazionez, Sergio Bevilaqua, Lia Rejane Müller Cammarota, Martín Pablo PKMζ memory reconsolidation Object recognition memory (ORM) confers the ability to discriminate the familiarity of previously encountered items. Reconsolidation is the process by which reactivated memories become labile and susceptible to modifications. The hippocampus is specifically engaged in reconsolidation to integrate new information into the original ORM through a mechanism involving activation of brain-derived neurotrophic factor (BDNF) signaling and induction of LTP. It is known that BDNF can control LTP maintenance through protein kinase Mζ (PKMζ), an atypical protein kinase C isoform that is thought to sustain memory storage by modulating glutamatergic neurotransmission. However, the potential involvement of PKMζ in ORM reconsolidation has never been studied. Using a novel ORM task combined with pharmacological, biochemical, and electrophysiological tools, we found that hippocampal PKMζ is essential to update ORM through reconsolidation, but not to maintain the inactive recognition memory trace stored over time, in adult male Wistar rats. Our results also indicate that hippocampal PKMζ acts downstream of BDNF and controls AMPAR synaptic insertion to elicit reconsolidation and suggest that blocking PKMζ activity during this process deletes active ORM.SIGNIFICANCE STATEMENT Object recognition memory (ORM) is essential to remember facts and events. Reconsolidation integrates new information into ORM through changes in hippocampal plasticity and brain-derived neurotrophic factor (BDNF) signaling. In turn, BDNF enhances synaptic efficacy through protein kinase Mζ (PKMζ), which might preserve memory. Here, we present evidence that hippocampal PKMζ acts downstream of BDNF to regulate AMPAR recycling during ORM reconsolidation and show that this kinase is essential to update the reactivated recognition memory trace, but not to consolidate or maintain an inactive ORM. We also demonstrate that the amnesia provoked by disrupting ORM reconsolidation through PKMζ inhibition is due to memory erasure and not to retrieval failure. 2019-03-13T19:31:55Z 2019-03-13T19:31:55Z 2019-03-06 article ROSSATO, J. I. et al. PKMζ inhibition disrupts reconsolidation and erases object recognition memory. J Neurosci., v. 39, n. 10, p. 1828-1841, mar. 2019. https://repositorio.ufrn.br/jspui/handle/123456789/26760 10.1523/JNEUROSCI.2270-18.2018 en application/pdf
institution Repositório Institucional
collection RI - UFRN
language English
topic PKMζ
memory
reconsolidation
spellingShingle PKMζ
memory
reconsolidation
Rossato, Janine I.
Gonzalez, Maria Carolina
Radiske, Andressa
Apolinário, Gênedy
Conde-Ocazionez, Sergio
Bevilaqua, Lia Rejane Müller
Cammarota, Martín Pablo
PKMζ inhibition disrupts reconsolidation and erases object recognition memory
description Object recognition memory (ORM) confers the ability to discriminate the familiarity of previously encountered items. Reconsolidation is the process by which reactivated memories become labile and susceptible to modifications. The hippocampus is specifically engaged in reconsolidation to integrate new information into the original ORM through a mechanism involving activation of brain-derived neurotrophic factor (BDNF) signaling and induction of LTP. It is known that BDNF can control LTP maintenance through protein kinase Mζ (PKMζ), an atypical protein kinase C isoform that is thought to sustain memory storage by modulating glutamatergic neurotransmission. However, the potential involvement of PKMζ in ORM reconsolidation has never been studied. Using a novel ORM task combined with pharmacological, biochemical, and electrophysiological tools, we found that hippocampal PKMζ is essential to update ORM through reconsolidation, but not to maintain the inactive recognition memory trace stored over time, in adult male Wistar rats. Our results also indicate that hippocampal PKMζ acts downstream of BDNF and controls AMPAR synaptic insertion to elicit reconsolidation and suggest that blocking PKMζ activity during this process deletes active ORM.SIGNIFICANCE STATEMENT Object recognition memory (ORM) is essential to remember facts and events. Reconsolidation integrates new information into ORM through changes in hippocampal plasticity and brain-derived neurotrophic factor (BDNF) signaling. In turn, BDNF enhances synaptic efficacy through protein kinase Mζ (PKMζ), which might preserve memory. Here, we present evidence that hippocampal PKMζ acts downstream of BDNF to regulate AMPAR recycling during ORM reconsolidation and show that this kinase is essential to update the reactivated recognition memory trace, but not to consolidate or maintain an inactive ORM. We also demonstrate that the amnesia provoked by disrupting ORM reconsolidation through PKMζ inhibition is due to memory erasure and not to retrieval failure.
format article
author Rossato, Janine I.
Gonzalez, Maria Carolina
Radiske, Andressa
Apolinário, Gênedy
Conde-Ocazionez, Sergio
Bevilaqua, Lia Rejane Müller
Cammarota, Martín Pablo
author_facet Rossato, Janine I.
Gonzalez, Maria Carolina
Radiske, Andressa
Apolinário, Gênedy
Conde-Ocazionez, Sergio
Bevilaqua, Lia Rejane Müller
Cammarota, Martín Pablo
author_sort Rossato, Janine I.
title PKMζ inhibition disrupts reconsolidation and erases object recognition memory
title_short PKMζ inhibition disrupts reconsolidation and erases object recognition memory
title_full PKMζ inhibition disrupts reconsolidation and erases object recognition memory
title_fullStr PKMζ inhibition disrupts reconsolidation and erases object recognition memory
title_full_unstemmed PKMζ inhibition disrupts reconsolidation and erases object recognition memory
title_sort pkmζ inhibition disrupts reconsolidation and erases object recognition memory
publishDate 2019
url https://repositorio.ufrn.br/jspui/handle/123456789/26760
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