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  Dual Regulation of Spine-Specific and Synapse-to-Nucleus Signaling by PKCδ during Plasticity

Colgan, L. A., Parra-Bueno, P., Holman, H. L., Tu, X., Jain, A., Calubag, M. F., et al. (2023). Dual Regulation of Spine-Specific and Synapse-to-Nucleus Signaling by PKCδ during Plasticity. The Journal of Neuroscience, (30). Retrieved from http://www.jneurosci.org/content/43/30/5432.abstract.

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Genre: Journal Article
Alternative Title : The Journal of Neuroscience

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 Creators:
Colgan, Lesley A.1, Author
Parra-Bueno, Paula1, Author
Holman, Heather L.1, Author
Tu, Xun1, Author
Jain, Anant1, Author
Calubag, Mariah F.1, Author
Misler, Jaime A.1, Author
Gary, Chancellor1, Author
Oz, Goksu1, Author
Suponitsky-Kroyter, Irena1, Author
Okaz, Elwy1, Author
Yasuda, Ryohei1, Author
Affiliations:
1Max Planck Florida Institute for Neuroscience, Max Planck Society, One Max Planck Way, Jupiter FL 33458, USA, ou_1950288              

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 Abstract: The activity-dependent plasticity of synapses is believed to be the cellular basis of learning. These synaptic changes are mediated through the coordination of local biochemical reactions in synapses and changes in gene transcription in the nucleus to modulate neuronal circuits and behavior. The protein kinase C (PKC) family of isozymes has long been established as critical for synaptic plasticity. However, because of a lack of suitable isozyme-specific tools, the role of the novel subfamily of PKC isozymes is largely unknown. Here, through the development of fluorescence lifetime imaging-fluorescence resonance energy transfer activity sensors, we investigate novel PKC isozymes in synaptic plasticity in CA1 pyramidal neurons of mice of either sex. We find that PKCδ is activated downstream of TrkB and DAG production, and that the spatiotemporal nature of its activation depends on the plasticity stimulation. In response to single-spine plasticity, PKCδ is activated primarily in the stimulated spine and is required for local expression of plasticity. However, in response to multispine stimulation, a long-lasting and spreading activation of PKCδ scales with the number of spines stimulated and, by regulating cAMP response-element binding protein activity, couples spine plasticity to transcription in the nucleus. Thus, PKCδ plays a dual functional role in facilitating synaptic plasticity.SIGNIFICANCE STATEMENT Synaptic plasticity, or the ability to change the strength of the connections between neurons, underlies learning and memory and is critical for brain health. The protein kinase C (PKC) family is central to this process. However, understanding how these kinases work to mediate plasticity has been limited by a lack of tools to visualize and perturb their activity. Here, we introduce and use new tools to reveal a dual role for PKCδ in facilitating local synaptic plasticity and stabilizing this plasticity through spine-to-nucleus signaling to regulate transcription. This work provides new tools to overcome limitations in studying isozyme-specific PKC function and provides insight into molecular mechanisms of synaptic plasticity.

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 Dates: 2023
 Publication Status: Issued
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Title: The Journal of Neuroscience
  Alternative Title : J. Neurosci.
Source Genre: Journal
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Pages: 5432 Volume / Issue: (30) Sequence Number: - Start / End Page: - Identifier: -