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Linking Mind to Molecular Pathways: The Role of Experiment Tools

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Abstract

Neurobiologists talk of linking mind to molecular dynamics in and between neurons. Such talk is dismissed by cognitive scientists, including many cognitive neuroscientists, due to the number of “levels” that separate behaviors from these molecular events. In this paper I explain what neurobiologists mean by such claims by describing the kinds of experiment tools that have forged these linkages, directly on lab benches. I here focus on one of these tools, gene targeting techniques, brought into behavioral neuroscience from developmental biology more than a quarter-century ago. Discussion of this tool does more than illuminate these claims by neurobiologists, however. An account of its development shows the doubly dependent role that theory plays in neurobiology. Our best current theories about “how the brain works” depend entirely on the experiment tools neuroscientists have available. And these tools get developed via the solution of engineering problems, not the application of theory. Theory is thus of tertiary importance in neuroscience, not of the primary importance that many cognitive scientists assume it to occupy.

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Notes

  1. I will say more about these techniques and their early development and successes in Sect. 4 below. The discussion to follow in this section draws on a more detailed account of gene targeting experiments in neurobiology in Bickle (2016, 3–9).

  2. Lisman’s model was a neurobiologically more specific version of Hebb’s (1949) famous “neurons that fire together, wire together” speculation.

  3. Morris and Kennedy drew their title from this line of Alexander Pope’s early-eighteenth century poem, “An Essay on Criticism.” The line of the couplet that precedes it, also quoted by Morris and Kennedy at the beginning of the review, is perhaps the most famous line from the poem: “A little learning is a dangerous thing.”

  4. This cell signaling pathway and its role in synaptic plasticity is so prominent in contemporary neuroscience that one finds detailed treatment of it in any good up-to-date textbook. I recommend Purves et al. (2018, chapter 7), especially for readers less familiar with molecular biology.

  5. See Bickle (2018) for a similar assessment and reproduction of a published page from Karl Diesseroth’s laboratory notebook depicting the initial schematic cartoon for the inserted light source for activating the light-sensitive receptor proteins used in optogenetics, a more recent tool in cellular physiology and behavioral neuroscience.

  6. In recent talks I have offered two additional case studies that illustrate all these points: the metal microelectrodue and the patch clamp. Bickle (in preparation) elaborates both cases.

References

  • Abel T, Nguyen PV, Barad M, Deuel TAS, Kandel ER, Bourtchouladze R (1997) Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory. Cell 88:615–626

    Google Scholar 

  • Bickle J (2003) Philosophy and neuroscience: a ruthlessly reductive account. Springer, Dordrecht

    Google Scholar 

  • Bickle J (2015) Marr and reductionism. Top Cogn Sci (TopiCS) 7(2):299–311

    Google Scholar 

  • Bickle J (2016) Revolutions in neuroscience: tool development. Front Syst Neurosci 10:24. https://doi.org/10.3389/fnsys.2016.00024

    Article  Google Scholar 

  • Bickle J (2018) From microscopes to optogenetics: Ian Hacking vindicated. Philos Sci 85(5):1065–1077

    Google Scholar 

  • Bickle J (in preparation) Tool development in neuroscience: putting theory in its place

  • Bickle J, Kostko A (2018) Connection experiments in neurobiology. Synthese 195:5271–5295

    Google Scholar 

  • Bliss TV, Lømo T (1973) Long-lasting potentiation of synaptic transmission in the anesthetized rabbit following stimulation of the perforant path. J Physiol 232(2):331–356

    Google Scholar 

  • Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schütz G, Silva AJ (1994) Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79(1):59–68

    Google Scholar 

  • Capecchi MR (2007) Gene targeting: 1977–present. Nobel Lecture, pp 155–172. https://www.nobelprize.org/nobel_prizes/medicine/laureates/2007/capecchi_lecture.pdf. Accessed 18 May 2019

  • Churchland PS (1986) Neurophilosophy. MIT Press, Cambridge

    Google Scholar 

  • Churchland PS, Sejnowski TJ (1992) The computational brain. MIT Press, Cambridge

    Google Scholar 

  • Churchland PS, Sejnowski TJ (2016) Blending computational and experimental neuroscience. Nat Rev Neurosci 17(11):667–668

    Google Scholar 

  • Craver CF (2007) Explaining the brain. Oxford University Press, New York

    Google Scholar 

  • Crick FHC (1979) Thinking about the brain. In: Scientific American (ed) The brain. Scientific American Books. W.H. Freeman and Co, San Francisco, pp 130–140

    Google Scholar 

  • Crick FHC, Koch C (2003) A framework for consciousness. Nat Neurosci 6:119–126

    Google Scholar 

  • Diesseroth K, Schnitzer MJ (2013) Engineering approaches to illuminating brain structure and function. Neuron 80(3):568–577

    Google Scholar 

  • Dudai Y (2002) Memory from A to Z. Oxford University Press, New York

    Google Scholar 

  • Evans MI (2007) Embryonic stem cells: the mouse source—vehicle for mammalian genetics and beyond. Nobel Lecture, pp 181–192. https://www.nobelprize.org/nobel_prizes/medicine/laureates/2007/evans_lecture.pdf. Accessed 18 May 2019

  • Folger KR, Thomas KR, Capecchi MR (1984) Analysis of homologous recombination in cultured mammalian cells. In: Cold spring harbor symposia on quantitative biology, vol 49, pp 123–138

    Google Scholar 

  • Gold I, Roskies AL (2008) Philosophy of neuroscience. In: Ruse M (ed) Oxford handbook of philosophy of biology. Oxford University Press, New York, pp 349–380

    Google Scholar 

  • Grant SGN, O’Dell TJ, Karl KA, Stein PL, Soriano P, Kandel ER (1992) Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice. Science 258:1903–1910

    Google Scholar 

  • Hacking I (1983) Representing and intervening: introductory topics in philosophy of natural science. Cambridge University Press, Cambridge

    Google Scholar 

  • Hebb D (1949) The organization of behavior. Wiley, New York

    Google Scholar 

  • Kandel ER, Schwartz JH, Jessell TM (2001) Principles of neural science, 4th edn. McGraw Hill, New York

    Google Scholar 

  • Kuhn TS (1962) The structure of scientific revolutions. University of Chicago Press, Chicago

    Google Scholar 

  • Lisman JE (1985) A mechanism for memory storage insensitive to molecular turnover: a bistable autophosphorylation kinase. Proc Natl Acad Sci USA 82:3055–3057

    Google Scholar 

  • Lisman JE, Goldring MA (1988) Feasibility of long-term storage of graded information by the Ca2 +/calmodulin-dependent protein kinase molecules of the postsynaptic density. Proc Natl Acad Sci USA 85:5320–5324

    Google Scholar 

  • Lynch G (1986) Synapses, circuits, and the beginnings of memory. MIT Press, Cambridge

    Google Scholar 

  • Lynch G, Larson J, Kelso S, Barrioneuvo G, Schottler F (1983) Intracellular injections of EGTA block induction of hippocampal long-term potentiation. Nature 305:710–721

    Google Scholar 

  • Marr D (1982) Vision. W.H. Freeman and Co, San Francisco

    Google Scholar 

  • Morris RG (1989) Synaptic plasticity and learning: selective impairment of learning rats and blockade of long-term potentiation in vivo by the N-methyl-aspartate receptor antagonist AP5. J Neurosci 9(9):3040–3057

    Google Scholar 

  • Morris RGM, Kennedy MB (1992) The pierrian spring. Curr Biol 2(10):511–515

    Google Scholar 

  • Mullis K, Faloona F, Sharf S, Horn G, Erlich H (1986) Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. In Cold spring harbor symposia on quantitative biology, vol 51. Cold Spring Harbor Laboratory Press, pp 263–273

  • Narayanamurti V, Odumosu T (2016) Cycles of invention and discovery: rethinking the endless frontier. Harvard University Press, Cambridge

    Google Scholar 

  • Potter H, Weir L, Leder P (1984) Enhancer-dependent expression of human kappa immunoglobin genes introduced into mouse pre-B lymphocytes by electroporation. Proc Natl Acad Sci USA 81(22):7161–7165

    Google Scholar 

  • Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia A-S, Mooney RD, Platt ML, White LE (2018) Neuroscience, 6th edn. Oxford University Press, New York

    Google Scholar 

  • Robins SK (2016) Optogenetics and the mechanisms of false memory. Synthese 193:1561–1583

    Google Scholar 

  • Robins SK (2018) Memory and optogenetic intervention: separating the engram from the ecphory. Philos Sci 85(5):1078–1089

    Google Scholar 

  • Silva AJ, Paylor R, Wehner JM, Tonegawa S (1992a) Impaired spatial learning in α-calcium-calmodulin kinase II mutant mice. Science 257:206–211

    Google Scholar 

  • Silva AJ, Stevens CF, Tonegawa S, Wang Y (1992b) Deficient hippocampal long-term potentiation in α-calcium-calmodulin kinase II mutant mice. Science 257:201–206

    Google Scholar 

  • Silva AJ, Landreth A, Bickel J (2014) Engineering the next revolution in neuroscience. Oxford University Press, New York

    Google Scholar 

  • Smithies O (2007) Turning pages. Nobel lecture, pp 209–230. https://www.nobelprize.org/nobel_prizes/medicine/laureates/2007/smithies_lecture.pdf. Accessed 18 May 2019

  • Sullivan JA (2009) The multiplicity of experimental protocols: a challenge to reduction and non-reductionist models of the unit of neuroscience. Synthese 167:511–539

    Google Scholar 

  • Sullivan JA (2010) Reconsidering ‘spatial memory’ and the Morris water maze. Synthese 177:261–283

    Google Scholar 

  • Sullivan JA (2018) Optogenetics, pluralism, and progress. Philos Sci 85(5):1090–1101

    Google Scholar 

  • Thomas KR, Capecchi MR (1987) Site-directed mutagenesis by gene targeting in mice embryo-derived stem cells. Cell 51(3):503–512

    Google Scholar 

Download references

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Bickle, J. Linking Mind to Molecular Pathways: The Role of Experiment Tools. Axiomathes 29, 577–597 (2019). https://doi.org/10.1007/s10516-019-09442-1

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