Abstract
Epigenetics investigates the dynamics of gene expression in various cells, and the signals from the internal and external environment affecting these dynamics. Neuroepigenetics extends this research into neurons and glia cells. Environmental-induced changes in gene expression are not only associated with the emerging structure and function of the nervous system during ontogeny, but are also fundamental to the wiring of neural circuitries responsible for learning and memory. Yet philosophers of science and neuroscience have so far paid little attention to these findings. In this article, we describe some recent experimental work on the neuroepigenetics of fear and stress responses in rodents, its ingenious experimental translation into humans, and how this work seems not to be accurately described by popular “mechanist” accounts. Our final goal is to motivate broader philosophical attention to neuroepigenetics practices and findings, especially for how it considers environmentally driven and developmental plasticity in psychological explanations.
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Notes
If the suspected cause is inhibitory, negative intervention experiments will increase the strength or probability of the effect. A related point holds for positive intervention experiments on inhibitory causes, to follow.
Interestingly, another neurobiologist active in the search for molecular mechanisms of memory, David Sweatt (2010), independently reached a framework of experiments closely related to Silva et al. (2014). His names are “blockage” (similar to negative manipulations), “mimicry” (similar to positive manipulations), and “measurements” (similar to correlational or non-interventions).
Again, we repeat our admission that philosophical accounts of mechanisms are much more diverse and fragmented than we can depict in a single paper, and that we are aware that this mechanisms 2.0/mechanisms 1.0 distinction may gloss over some important differences already in the published literature.
In this article, we are stressing the role that environmental stimuli play in organisms’ development, as shown by epigenetic research. However, in no way are we siding with an “externalist” view of development, at least not one where “externalism” is the view that the environment principally constraints and triggers the expression of genes, while internal factors such as genes are not acknowledged as full-fledged causes of biological changes. We insist that much biological research has shown that both internal (e.g., genetics) and external factors exert specific, nonredundant causal control over the ontogeny and functions of an organism (see Burnston and Tramacere 2023 for detailed discussion of this point).
Note that the research on intergenerational inheritance of epigenetic markers is still under intense debate, and it remains an open question whether the molecular effects of environmentally-driven phenotypic changes can be inherited by different generations without the initial environmental stimuli being present during the offspring lifespan (see Curley et al. 2023).
References
Albert PR, Benkelfat C (2013) The neurobiology of depression—revisiting the serotonin hypothesis. II. Genetic, epigenetic and clinical studies†. Philos Trans Royal Soc B: Biol Sci 368(1615):20120535. https://doi.org/10.1098/rstb.2012.0535
Baedke J (2018) Above the gene, beyond biology: toward a philosophy of epigenetics. University of Pittsburgh Press, Pittsburgh
Barwich A-S (2021) Imaging the living brain: an argument for ruthless reductionism from olfactory neurobiology. J Theor Biol 512:110560
Bechtel W (2007) Discovering cell mechanisms: the creation of modern cell biology. J Hist Biol 40(1):185–187
Bechtel W (2009) Looking down, around, and up: mechanistic explanation in psychology. Philos Psychol 22(5):543–564. https://doi.org/10.1080/09515080903238948
Bechtel W (2010) The downs and ups of mechanistic research: circadian rhythm research as an exemplar. Erkenntnis 73(3):313–328. https://doi.org/10.1007/s10670-010-9234-2
Bechtel W (2016) Mechanists must be holists too! Perspectives from circadian biology. J Hist Biol 49(4):705–731. https://doi.org/10.1007/s10739-016-9439-6
Bechtel W (2017) Explicating top-down causation using networks and dynamics. Philos Sci 84(2):253–274. https://doi.org/10.1086/690718
Bechtel W, Abrahamsen AA (2013) Thinking dynamically about biological mechanisms: networks of coupled oscillators: philosophy and complexity. Found Sci 18(4):707–723
Bechtel W, Huang LT-L (2022) Philosophy of neuroscience. Elements in philosophy of mind. https://doi.org/10.1017/9781108946964
Bickle J (2006) Reducing mind to molecular pathways: explicating the reductionism implicit in cellular and molecular neuroscience. Synthese 151:411–434
Bickle J (2020) Laser lights and designer drugs: new techniques for descending levels of mechanisms “in a single bound.” TopiCS 12:1241–1256
Bickle J, Barwich A-S (2022) Introduction to molecular and cellular cognition. Mind, cognition, and neuroscience. Routledge, New York
Bickle J, Kostko A (2018) Connection experiments in neurobiology. Synthese 195(12):5271–5295. https://doi.org/10.1007/s11229-018-1838-0
Brigandt I (2015) Evolutionary developmental biology and the limits of philosophical accounts of mechanistic explanation. In: Braillard P-A, Malaterre C (eds) Explanation in biology: an enquiry into the diversity of explanatory patterns in the life sciences. Springer, Dordrecht, pp 135–173
Burnston D, Tramacere, A (2023). Distributed loci of control: overcoming stale dichotomies in biology and cognitive science. Rivista Italiana di Filosofia e Psicologia. (In Press).
Craver CF, Bechtel W (2007) Top-down causation without top-down causes. Biol Philos 22(4):547–563. https://doi.org/10.1007/s10539-006-9028-8
Curley, JP, Mashoodh, R, Champagne, FA (2023) Transgenerational epigenetics. Handbook of Epigenetics. pp. 465–478
Day JJ, Sweatt JD (2011) Cognitive neuroepigenetics: a role for epigenetic mechanisms in learning and memory. Neurobiol Learn Mem 96(1):2–12. https://doi.org/10.1016/j.nlm.2010.12.008
Eronen MI (2013) No levels, no problems: downward causation in neuroscience. Philos Sci 80(5):1042–1052. https://doi.org/10.1086/673898
Feldman R, Monakhov M, Pratt M, Ebstein RP (2016) Oxytocin pathway genes: evolutionary ancient system impacting on human affiliation, sociality, and psychopathology. Biol Psychiatry 79(3):174–184. https://doi.org/10.1016/j.biopsych.2015.08.008
Francis DD, Caldji C, Champagne F, Plotsky PM, Meaney MJ (1999) The role of corticotropin-releasing factor–norepinephrine systems in mediating the effects of early experience on the development of behavioral and endocrine responses to stress. Biol Psychiatry 46(9):1153–1166. https://doi.org/10.1016/S0006-3223(99)00237-1
Glennan S (2002) Rethinking mechanistic explanation. Philos Sci 69(S3):S342–S353. https://doi.org/10.1086/341857
Gräff J, Joseph NF, Horn ME, Samiei A, Meng J, Seo J et al (2014) Epigenetic priming of memory updating during reconsolidation to attenuate remote fear memories. Cell 156(1):261–276. https://doi.org/10.1016/j.cell.2013.12.020
Hall BK (1992) Genetics, epigenetics and environment. In: Hall BK (ed) Evolutionary developmental biology. Springer, Dordrecht, pp 150–182. https://doi.org/10.1007/978-94-015-7926-1_9
Jablonka E, Lamb MJ (1989) The inheritance of acquired epigenetic variations. J Theor Biol 139(1):69–83. https://doi.org/10.1016/S0022-5193(89)80058-X
Jablonka E, Lamb MJ (2005) Evolution in four dimensions: genetic, epigenetic, behavioral, and symbolic variation in the history of life (pp. x, 462). MIT Press, Cambridge
Kaplan DM, Craver CF (2011) The explanatory force of dynamical and mathematical models in neuroscience: a mechanistic perspective. Philos Sci 78(4):601–627. https://doi.org/10.1086/661755
Keverne EB, Pfaff DW, Tabansky I (2015) Epigenetic changes in the developing brain: effects on behavior. Proc Nat Acad Sci USA, 112(22), 6789–6795. https://doi.org/10.1073/pnas.1501482112
Labonté B, Suderman M, Maussion G, Navaro L, Yerko V, Mahar I et al (2012) Genome-wide epigenetic regulation by early-life trauma. Arch Gen Psychiatry 69(7):722–731. https://doi.org/10.1001/archgenpsychiatry.2011.2287
Levy A, Bechtel W (2016) Towards mechanism 2.0: expanding the scope of mechanistic explanation. Paper presented at the Biennial Meeting of the Philosophy of Science Association, Atlanta, November 3–6
Love A, Stewart T, Wagner G, Newman S (2017) Perspectives on integrating genetic and physical explanations of evolution and development: an introduction to the symposium. Integra Comp Biol 57(6):1258–1268. https://doi.org/10.1093/icb/icx121
Machamer P, Darden L, Craver CF (2000) Thinking about mechanisms. Philos Sci 67(1):1–25. https://doi.org/10.1086/392759
McEwen BS, Eiland L, Hunter RG, Miller MM (2012) Stress and anxiety: structural plasticity and epigenetic regulation as a consequence of stress. Neuropharm 62(1):3–12. https://doi.org/10.1016/j.neuropharm.2011.07.014
McGowan PO, Sasaki A, D’Alessio AC, Dymov S, Labonté B, Szyf M, Turecki G, Meaney MJ (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12(3):342–348. https://doi.org/10.1038/nn.2270
Mc Manus F (2012) Development and mechanistic explanation. Stud Hist Philos Biol Biomed Sci C Stud History Philos Biolog Biomed Sci 43(2):532–541. https://doi.org/10.1016/j.shpsc.2011.12.001
Miguel PM, Pereira LO, Silveira PP, Meaney MJ (2019) Early environmental influences on the development of children’s brain structure and function. Dev Med Child Neurol 61(10):1127–1133. https://doi.org/10.1111/dmcn.14182
Nathan MJ (2014) Causation by concentration. Br J Philos Sci 65(2):191–212
Potochnik A, McGill B (2012) The limitations of hierarchical organization. Philos Sci 79(1):120–140. https://doi.org/10.1086/663237
Robins SK, Craver CF (2009) Biological clocks: explaining with models of mechanisms. In: Bickle J (ed) The Oxford handbook of philosophy and neuroscience. Oxford University Press, New York, pp 41–67
Roe SM, Baumgaertner B (2017) Extended mechanistic explanations: expanding the current mechanistic conception to include more complex biological systems. J Gen Philos Sci 48(4):517–534. https://doi.org/10.1007/s10838-016-9356-6
Ross LN (2021) Causal concepts in biology: how pathways differ from mechanisms and why it matters. Br J Philos Sci 72(1):131–158
Sarto-Jackson I (2022) The making and breaking of minds: how social interactions shape the human mind. Vernon Press, Wilmington. https://vernonpress.com/book/387
Silva AJ, Landreth A, Bickle J (2014) Engineering the next revolution in neuroscience: the new science of experiment planning. Oxford University Press, New York
Sterner EY, Kalynchuk LE (2010) Behavioral and neurobiological consequences of prolonged glucocorticoid exposure in rats: relevance to depression. Prog Neuropsychopharmacol Biol Psychiatry 34(5):777–790. https://doi.org/10.1016/j.pnpbp.2010.03.005
Sweatt JD (2010) Mechanisms of memory, 2nd edn. Elsevier Academic Press, Cambridge
Weaver ICG, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR et al (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7(8):847–854. https://doi.org/10.1038/nn1276
Weaver ICG, Champagne FA, Brown SE, Dymov S, Sharma S, Meaney MJ, Szyf M (2005) Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life. J Neurosci 25(47):11045–11054. https://doi.org/10.1523/JNEUROSCI.3652-05.2005
Weinberger N (2017) Mechanisms without mechanistic explanation. Synthese 196:2323–2340. https://doi.org/10.1007/s11229-017-1538-1
Woodward J (2003) Making things happen: a theory of causal explanation. https://doi.org/10.1111/j.1933-1592.2007.00012.x
Woodward J (2015) Methodology, ontology, and interventionism. Synthese 192(11):3577–3599. https://doi.org/10.1007/s11229-014-0479-1
Ylikoski P (2013) Causal and constitutive explanation compared. Erkenntnis 78(2):277–297. https://doi.org/10.1007/s10670-013-9513-9
Young BD, Jennings CD (2022) Mind, cognition, and neuroscience: a philosophical introduction. Routledge, New York
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Tramacere, A., Bickle, J. Neuroepigenetics in Philosophical Focus: A Critical Analysis of the Philosophy of Mechanisms. Biol Theory 19, 56–71 (2024). https://doi.org/10.1007/s13752-023-00435-3
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DOI: https://doi.org/10.1007/s13752-023-00435-3