Optogenetically induced cellular habituation in non-neuronal cells

Autoři: Mattia Bonzanni aff001;  Nicolas Rouleau aff001;  Michael Levin aff002;  David L. Kaplan aff001
Působiště autorů: Department of Biomedical Engineering, Allen Discovery Center, Tufts University, Medford, United States of America aff001;  Department of Biology, Allen Discovery Center, Tufts University, Medford, United States of America aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227230


Habituation, defined as the reversible decrement of a response during repetitive stimulation, is widely established as a form of non-associative learning. Though more commonly ascribed to neural cells and systems, habituation has also been observed in single aneural cells, although evidence is limited. Considering the generalizability of the habituation process, we tested the degree to which organism-level behavioral and single cell manifestations were similar. Human embryonic kidney (HEK) cells that overexpressed an optogenetic actuator were photostimulated to test the effect of different stimulation protocols on cell responses. Depolarization induced by the photocurrent decreased successively over the stimulation protocol and the effect was reversible upon withdrawal of the stimulus. In addition to frequency- and intensity-dependent effects, the history of stimulations on the cells impacted subsequent depolarization in response to further stimulation. We identified tetraethylammonium (TEA)-sensitive native K+ channels as one of the mediators of this habituation phenotype. Finally, we used a theoretical model of habituation to elucidate some mechanistic aspects of the habituation response. In conclusion, we affirm that habituation is a time- and state-dependent biological strategy that can be adopted also by individual non-neuronal cells in response to repetitive stimuli.

Klíčová slova:

Depolarization – Functional electrical stimulation – HEK 293 cells – Kidneys – Learning – Light pulses – Optogenetics – Potassium channels


1. Rankin CH, Abrams T, Barry RJ, Bhatnagar S, Clayton D, Colombo J et al. (2009) Habituation revisited: an updated and revised description of the behavioral characteristics of habituation. Neurobiol Learn Mem 92(2):135–138. doi: 10.1016/j.nlm.2008.09.012 18854219

2. Thompson RF & Spencer WA (1966) Habituation: a model phenomenon for the study of neuronal substrates of behavior. Psychol Rev 73(1):16–43. doi: 10.1037/h0022681 5324565

3. Groves PM & Thompson RF (1970) Habituation: a dual-process theory. Psychol Rev 77(5):419–450. doi: 10.1037/h0029810 4319167

4. Sokolov EN (1963) Higher nervous functions; the orienting reflex. Annu Rev Physiol 25:545–580. doi: 10.1146/annurev.ph.25.030163.002553 13977960

5. Ramaswami M (2014) Network plasticity in adaptive filtering and behavioral habituation. Neuron 82(6):1216–1229. doi: 10.1016/j.neuron.2014.04.035 24945768

6. Bonzanni M, Rouleau N, Levin M, & Kaplan DL (2019) On the Generalization of Habituation: How Discrete Biological Systems Respond to Repetitive Stimuli: A Novel Model of Habituation That Is Independent of Any Biological System. Bioessays 41(7):e1900028. doi: 10.1002/bies.201900028 31222777

7. Boisseau RP, Vogel D, & Dussutour A (2016) Habituation in non-neural organisms: evidence from slime moulds. Proc. R. Soc. B 283(1829):20160446. doi: 10.1098/rspb.2016.0446 27122563

8. Eisenstein E, Brunder D, & Blair H (1982) Habituation and sensitization in an aneural cell: Some comparative and theoretical considerations. Neuroscience & Biobehavioral Reviews 6(2):183–194.

9. Meins F Jr & Lutz J (1979) Tissue-specific variation in the cytokinin habituation of cultured tobacco cells. Differentiation 15(1–3):1–6.

10. Pischke MS, Huttlin EL, Hegeman AD, & Sussman MR (2006) A transcriptome-based characterization of habituation in plant tissue culture. Plant Physiology 140(4):1255–1278. doi: 10.1104/pp.105.076059 16489130

11. Lyon P (2006) The biogenic approach to cognition. Cogn Process 7(1):11–29. doi: 10.1007/s10339-005-0016-8 16628463

12. Baluska F & Levin M (2016) On Having No Head: Cognition throughout Biological Systems. Front Psychol 7:902. doi: 10.3389/fpsyg.2016.00902 27445884

13. Katz Y, Yizhar O, Staiger J, & Lampl I (2013) Optopatcher—an electrode holder for simultaneous intracellular patch-clamp recording and optical manipulation. J Neurosci Methods 214(1):113–117. doi: 10.1016/j.jneumeth.2013.01.017 23370312

14. Ponce A, Castillo A, Hinojosa L, Martinez-Rendon J, & Cereijido M (2018) The expression of endogenous voltage-gated potassium channels in HEK293 cells is affected by culture conditions. Physiol Rep 6(8):e13663. doi: 10.14814/phy2.13663 29665277

Článek vyšel v časopise


2020 Číslo 1
Nejčtenější tento týden