The first two decades of CREB-memory research: data for philosophy of neuroscience

John Bickle; John Bickle

doi:10.3934/Neuroscience.2021017

AIMS Neuroscience

2021, Volume 8, Issue 3: 322-339. doi: 10.3934/Neuroscience.2021017

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The first two decades of CREB-memory research: data for philosophy of neuroscience

John Bickle ^,

Department of Philosophy, Mississippi State University; Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center. USA

Received: 10 January 2021 Accepted: 19 February 2021 Published: 22 February 2021

I recount some landmark discoveries that initially confirmed the cyclic AMP response element-binding (CREB) protein-memory consolidation and allocation linkages. This work constitutes one of the successes of the field of Molecular and Cellular Cognition (MCC) but is also of interest to philosophers of neuroscience. Two approaches, “mechanism” and “ruthless reductionism”, claim to account for this case, yet these accounts differ in one crucial way. I explain this difference and argue that both the experiment designs and discussions of these discoveries by MCC scientists better fit the ruthless reductionist's account. This conclusion leads to further philosophical discussion about how discoveries in cellular/molecular neurobiology integrate with systems neuroscience findings.
- cyclic adenosine monophosphate response element-binding protein (CREB),
- memory consolidation,
- memory allocation,
- ruthless reductionism,
- mechanism
Citation: John Bickle. The first two decades of CREB-memory research: data for philosophy of neuroscience[J]. AIMS Neuroscience, 2021, 8(3): 322-339. doi: 10.3934/Neuroscience.2021017

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Abstract

I recount some landmark discoveries that initially confirmed the cyclic AMP response element-binding (CREB) protein-memory consolidation and allocation linkages. This work constitutes one of the successes of the field of Molecular and Cellular Cognition (MCC) but is also of interest to philosophers of neuroscience. Two approaches, “mechanism” and “ruthless reductionism”, claim to account for this case, yet these accounts differ in one crucial way. I explain this difference and argue that both the experiment designs and discussions of these discoveries by MCC scientists better fit the ruthless reductionist's account. This conclusion leads to further philosophical discussion about how discoveries in cellular/molecular neurobiology integrate with systems neuroscience findings.

Conflict of interest

The author declares no conflict of interest.

¹ Isoforms are structurally very similar proteins, originating from a single gene or gene family. The functions of different isoforms of the same protein can differ significantly, as in the case of CREB.

² This discussion oversimplifies a very complex CREB molecular genetics. The context of the CRE binding sites and the regulation of the particular promoter also help determine whether CREB dimerization and binding activates or represses gene expression at that site.

³ My presentation of both the scientific details and the history in this section has been aided by very helpful remarks on a previous draft by Wayne Sossin.

⁴ See [8] for a survey of some landmark results of the first two decades (1992–2012) of MCC. Since 2000 there has been a scientific society, the Molecular and Cellular Cognition Society, with a worldwide membership, affiliates in Europe and Asia, and an annual meeting held each year in conjunction with the Society for Neuroscience annual meeting, along with affiliate meetings. See https://molcellcog.org/ (queried December 9, 2020).

⁵ Generating viable homologous CREB α/δ-knock-out mice turned out to be no easy task; A detailed account of the generation of Schütz's mutants is provided in [9]. The last sentence of [9] reads: “The relatively high abundance of CREB protein in brain ... and recent data implicating cAMP-inducing genes in long-term potentiation [citing [4], discussed above] and the maintenance of circadian rhythms make the CREB -/- mouse a useful model to study selective effects on neuronal function.” So it turned out to be, as we are about to see.

⁶ A much-cited review is [12].

⁷ These early transgenic techniques differ from today's CRISPR-cas9 technologies, as unlike the latter they afforded little control over where the transgene gets inserted into the DNA molecule.

⁸ For a review see [21].

⁹ Thanks to David Colaço who emphasized to me the importance of spelling out this difference between these two philosophies of neuroscience.

¹⁰ For an excellent recent example of how to do these structured interviews fruitfully and responsibly see [28].

¹¹ I thank Wayne Sossin for raising concerns about this section in an earlier draft that required me to more clearly state the methods and limitations of metascience.

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