Abstract
The excitation-inhibition (E-I) imbalance in neural circuits represents a hallmark of several neuropsychiatric disorders. The tiny nematode Caenorhabditis elegans has emerged as an excellent system to study the molecular mechanisms underlying this imbalance in neuronal circuits. The C. elegans body wall muscles receive inputs from both excitatory cholinergic and inhibitory GABAergic motor neurons at neuromuscular junctions (NMJ), making it an excellent model for studying the genetic and molecular mechanisms required for maintaining E-I balance at the NMJ. The cholinergic neurons form dyadic synapses wherein they synapse onto ipsilateral body wall muscles allowing for muscle contraction as well as onto GABAergic motor neurons that in turn synapse on the contralateral body wall muscles causing muscle relaxation. An alternating wave of contraction and relaxation mediated by excitatory and inhibitory signals maintains locomotion in C. elegans. This locomotory behavior requires an intricate balance between the excitatory cholinergic signaling and the inhibitory GABAergic signaling mechanisms.
Studies on the C. elegans NMJ have provided insights into several molecular mechanisms that could regulate this balance in neural circuits. This review provides a discussion on multiple genetic factors including neuropeptides and their receptors, cell adhesion molecules, and other molecular pathways that have been associated with maintaining E-I balance in C. elegans motor circuits. Further, it also discusses the implications of these studies that could help us in understanding the role of E-I balance in mammalian neural circuits and how changes in this balance could give rise to brain disorders.
Keywords
- Excitation
- Inhibition
- Acetylcholine
- GABA
- NMJ
- C. elegans
This is a preview of subscription content, access via your institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Artan M, Jeong DE, Lee D, Kim YI, Son HG, Husain Z, Kim J, Altintas O, Kim K, Alcedo J, Lee SJ (2016) Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides. Genes Dev 30:1047–1057
Banerjee N, Bhattacharya R, Gorczyca M, Collins KM, Francis MM (2017) Local neuropeptide signaling modulates serotonergic transmission to shape the temporal organization of C. elegans egg-laying behavior. PLoS Genet 13:e1006697
Bargmann CI (2012) Beyond the connectome: how neuromodulators shape neural circuits. Bioessays 34:458–465
Bargmann CI, Horvitz HR (1991) Chemosensory neurons with overlapping functions direct chemotaxis to multiple chemicals in C. elegans. Neuron 7:729–742
Bargmann CI, Hartwieg E, Horvitz HR (1993) Odorant-selective genes and neurons mediate olfaction in C. elegans. Cell 74:515–527
Bhardwaj A, Thapliyal S, Dahiya Y, Babu K (2018) FLP-18 functions through the G-protein-coupled receptors NPR-1 and NPR-4 to modulate reversal length in Caenorhabditis elegans. J Neurosci Off J Soc Neurosci 38:4641–4654
Blackmore M, Letourneau PC (2006) L1, beta1 integrin, and cadherins mediate axonal regeneration in the embryonic spinal cord. J Neurobiol 66:1564–1583
Braeckman BP, Vanfleteren JR (2007) Genetic control of longevity in C. elegans. Exp Gerontol 42:90–98
Braunewell KH (2005) The darker side of Ca2+ signaling by neuronal Ca2+-sensor proteins: from Alzheimer’s disease to cancer. Trends Pharmacol Sci 26:345–351
Braunewell KH, Gundelfinger ED (1999) Intracellular neuronal calcium sensor proteins: a family of EF-hand calcium-binding proteins in search of a function. Cell Tissue Res 295:1–12
Bretscher AJ, Kodama-Namba E, Busch KE, Murphy RJ, Soltesz Z, Laurent P, de Bono M (2011) Temperature, oxygen, and salt-sensing neurons in C. elegans are carbon dioxide sensors that control avoidance behavior. Neuron 69:1099–1113
Burgoyne RD (2007) Neuronal calcium sensor proteins: generating diversity in neuronal Ca2+ signalling. Nat Rev Neurosci 8:182–193
Burgoyne RD, Haynes LP (2012) Understanding the physiological roles of the neuronal calcium sensor proteins. Mol Brain 5:2
Cavallaro U, Dejana E (2011) Adhesion molecule signalling: not always a sticky business. Nat Rev Mol Cell Biol 12:189–197
Chalasani SH, Kato S, Albrecht DR, Nakagawa T, Abbott LF, Bargmann CI (2010) Neuropeptide feedback modifies odor-evoked dynamics in Caenorhabditis elegans olfactory neurons. Nat Neurosci 13:615–621
Chalfie M, Sulston JE, White JG, Southgate E, Thomson JN, Brenner S (1985) The neural circuit for touch sensitivity in Caenorhabditis elegans. J Neurosci Off J Soc Neurosci 5:956–964
Chang YJ, Burton T, Ha L, Huang Z, Olajubelo A, Li C (2015) Modulation of locomotion and reproduction by FLP neuropeptides in the nematode Caenorhabditis elegans. PLoS One 10:e0135164
Chen YC, Chen HJ, Tseng WC, Hsu JM, Huang TT, Chen CH, Pan CL (2016) A C. elegans thermosensory circuit regulates longevity through crh-1/CREB-dependent flp-6 neuropeptide signaling. Dev Cell 39(2):209–223
Cheng A, McDonald NA, Connolly CN (2005) Cell surface expression of 5-hydroxytryptamine type 3 receptors is promoted by RIC-3. J Biol Chem 280:22502–22507
Cheong MC, Artyukhin AB, You YJ, Avery L (2015) An opioid-like system regulating feeding behavior in C. elegans. elife 4:e06683
Chih B, Engelman H, Scheiffele P (2005) Control of excitatory and inhibitory synapse formation by neuroligins. Science 307:1324–1328
Cornils A, Gloeck M, Chen Z, Zhang Y, Alcedo J (2011) Specific insulin-like peptides encode sensory information to regulate distinct developmental processes. Development 138:1183–1193
Cremer H, Chazal G, Goridis C, Represa A (1997) NCAM is essential for axonal growth and fasciculation in the hippocampus. Mol Cell Neurosci 8:323–335
Culetto E, Baylis HA, Richmond JE, Jones AK, Fleming JT, Squire MD, Lewis JA, Sattelle DB (2004) The Caenorhabditis elegans unc-63 gene encodes a levamisole-sensitive nicotinic acetylcholine receptor alpha subunit. J Biol Chem 279:42476–42483
Culotti JG, Russell RL (1978) Osmotic avoidance defective mutants of the nematode Caenorhabditis elegans. Genetics 90:243–256
Dalva MB, McClelland AC, Kayser MS (2007) Cell adhesion molecules: signalling functions at the synapse. Nat Rev Neurosci 8:206–220
de Bono M, Maricq AV (2005) Neuronal substrates of complex behaviors in C. elegans. Annu Rev Neurosci 28:451–501
Delaney CE, Chen AT, Graniel JV, Dumas KJ, Hu PJ (2017) A histone H4 lysine 20 methyltransferase couples environmental cues to sensory neuron control of developmental plasticity. Development 144:1273–1282
Eichler SA, Meier JC (2008) E-I balance and human diseases – from molecules to networking. Front Mol Neurosci 1:2
Engel AG, Ohno K, Milone M, Wang HL, Nakano S, Bouzat C, Pruitt JN II, Hutchinson DO, Brengman JM, Bren N, Sieb JP, Sine SM (1996) New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome. Hum Mol Genet 5:1217–1227
Flaherty KM, Zozulya S, Stryer L, McKay DB (1993) Three-dimensional structure of recoverin, a calcium sensor in vision. Cell 75:709–716
Fleming JT, Squire MD, Barnes TM, Tornoe C, Matsuda K, Ahnn J, Fire A, Sulston JE, Barnard EA, Sattelle DB, Lewis JA (1997) Caenorhabditis elegans levamisole resistance genes lev-1, unc-29, and unc-38 encode functional nicotinic acetylcholine receptor subunits. J Neurosci Off J Soc Neurosci 17:5843–5857
Francis MM, Evans SP, Jensen M, Madsen DM, Mancuso J, Norman KR, Maricq AV (2005) The Ror receptor tyrosine kinase CAM-1 is required for ACR-16-mediated synaptic transmission at the C. elegans neuromuscular junction. Neuron 46:581–594
Graf ER, Zhang X, Jin SX, Linhoff MW, Craig AM (2004) Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell 119:1013–1026
Halevi S, McKay J, Palfreyman M, Yassin L, Eshel M, Jorgensen E, Treinin M (2002) The C. elegans ric-3 gene is required for maturation of nicotinic acetylcholine receptors. EMBO J 21:1012–1020
Halevi S, Yassin L, Eshel M, Sala F, Sala S, Criado M, Treinin M (2003) Conservation within the RIC-3 gene family. Effectors of mammalian nicotinic acetylcholine receptor expression. J Biol Chem 278:34411–34417
Hansen SM, Berezin V, Bock E (2008) Signaling mechanisms of neurite outgrowth induced by the cell adhesion molecules NCAM and N-cadherin. Cell Mol Life Sci 65:3809–3821
Harris G, Mills H, Wragg R, Hapiak V, Castelletto M, Korchnak A, Komuniecki RW (2010) The monoaminergic modulation of sensory-mediated aversive responses in Caenorhabditis elegans requires glutamatergic/peptidergic cotransmission. J Neurosci Off J Soc Neurosci 30:7889–7899
Hedgecock EM, Russell RL (1975) Normal and mutant thermotaxis in the nematode Caenorhabditis elegans. Proc Natl Acad Sci U S A 72:4061–4065
Hintsch G, Zurlinden A, Meskenaite V, Steuble M, Fink-Widmer K, Kinter J, Sonderegger P (2002) The calsyntenins – a family of postsynaptic membrane proteins with distinct neuronal expression patterns. Mol Cell Neurosci 21:393–409
Hirano S, Takeichi M (2012) Cadherins in brain morphogenesis and wiring. Physiol Rev 92:597–634
Hu Z, Pym EC, Babu K, Vashlishan Murray AB, Kaplan JM (2011) A neuropeptide-mediated stretch response links muscle contraction to changes in neurotransmitter release. Neuron 71:92–102
Hu Z, Vashlishan-Murray AB, Kaplan JM (2015) NLP-12 engages different UNC-13 proteins to potentiate tonic and evoked release. J Neurosci Off J Soc Neurosci 35:1038–1042
Hung WL, Wang Y, Chitturi J, Zhen M (2014) A Caenorhabditis elegans developmental decision requires insulin signaling-mediated neuron-intestine communication. Development 141:1767–1779
Ikeda DD, Duan Y, Matsuki M, Kunitomo H, Hutter H, Hedgecock EM, Iino Y (2008) CASY-1, an ortholog of calsyntenins/alcadeins, is essential for learning in Caenorhabditis elegans. Proc Natl Acad Sci U S A 105:5260–5265
Isaacson JS, Scanziani M (2011) How inhibition shapes cortical activity. Neuron 72:231–243
Jones AK, Sattelle DB (2004) Functional genomics of the nicotinic acetylcholine receptor gene family of the nematode, Caenorhabditis elegans. Bioessays 26:39–49
Jospin M, Qi YB, Stawicki TM, Boulin T, Schuske KR, Horvitz HR, Bessereau JL, Jorgensen EM, Jin Y (2009) A neuronal acetylcholine receptor regulates the balance of muscle excitation and inhibition in Caenorhabditis elegans. PLoS Biol 7:e1000265
Kao G, Nordenson C, Still M, Ronnlund A, Tuck S, Naredi P (2007) ASNA-1 positively regulates insulin secretion in C. elegans and mammalian cells. Cell 128:577–587
Kaplan JM, Horvitz HR (1993) A dual mechanosensory and chemosensory neuron in Caenorhabditis elegans. Proc Natl Acad Sci U S A 90:2227–2231
Ko J, Fuccillo MV, Malenka RC, Sudhof TC (2009) LRRTM2 functions as a neurexin ligand in promoting excitatory synapse formation. Neuron 64:791–798
Konecna A, Frischknecht R, Kinter J, Ludwig A, Steuble M, Meskenaite V, Indermuhle M, Engel M, Cen C, Mateos JM, Streit P, Sonderegger P (2006) Calsyntenin-1 docks vesicular cargo to kinesin-1. Mol Biol Cell 17:3651–3663
Lansdell SJ, Gee VJ, Harkness PC, Doward AI, Baker ER, Gibb AJ, Millar NS (2005) RIC-3 enhances functional expression of multiple nicotinic acetylcholine receptor subtypes in mammalian cells. Mol Pharmacol 68:1431–1438
Laurent P, Soltesz Z, Nelson GM, Chen C, Arellano-Carbajal F, Levy E, de Bono M (2015) Decoding a neural circuit controlling global animal state in C. elegans. elife 4:4
Lei M, Xu H, Li Z, Wang Z, O’Malley TT, Zhang D, Walsh DM, Xu P, Selkoe DJ, Li S (2016) Soluble Abeta oligomers impair hippocampal LTP by disrupting glutamatergic/GABAergic balance. Neurobiol Dis 85:111–121
Leinwand SG, Chalasani SH (2013) Neuropeptide signaling remodels chemosensory circuit composition in Caenorhabditis elegans. Nat Neurosci 16:1461–1467
Leinwand SG, Chalasani SH (2014) From genes to circuits and behaviors: neuropeptides expand the coding potential of the nervous system. WormBook 3:e27730
Lewis JA, Wu CH, Berg H, Levine JH (1980) The genetics of levamisole resistance in the nematode Caenorhabditis elegans. Genetics 95:905–928
Li C, Kim K (2008) Neuropeptides. WormBook 25:1–36
Li C, Timbers TA, Rose JK, Bozorgmehr T, McEwan A, Rankin CH (2013) The FMRFamide-related neuropeptide FLP-20 is required in the mechanosensory neurons during memory for massed training in C. elegans. Learn Mem 20:103–108
Linhoff MW, Lauren J, Cassidy RM, Dobie FA, Takahashi H, Nygaard HB, Airaksinen MS, Strittmatter SM, Craig AM (2009) An unbiased expression screen for synaptogenic proteins identifies the LRRTM protein family as synaptic organizers. Neuron 61:734–749
Mann EO, Mody I (2008) The multifaceted role of inhibition in epilepsy: seizure-genesis through excessive GABAergic inhibition in autosomal dominant nocturnal frontal lobe epilepsy. Curr Opin Neurol 21:155–160
McGrath PT, Xu Y, Ailion M, Garrison JL, Butcher RA, Bargmann CI (2011) Parallel evolution of domesticated Caenorhabditis species targets pheromone receptor genes. Nature 477:321–325
Missler M, Sudhof TC, Biederer T (2012) Synaptic cell adhesion. Cold Spring Harb Perspect Biol 4:a005694
Mori I, Ohshima Y (1995) Neural regulation of thermotaxis in Caenorhabditis elegans. Nature 376:344–348
Muchowski PJ, Wacker JL (2005) Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci 6:11–22
Nacher J, Guirado R, Castillo-Gomez E (2013) Structural plasticity of interneurons in the adult brain: role of PSA-NCAM and implications for psychiatric disorders. Neurochem Res 38:1122–1133
Nagy S, Tramm N, Sanders J, Iwanir S, Shirley IA, Levine E, Biron D (2014) Homeostasis in C. elegans sleep is characterized by two behaviorally and genetically distinct mechanisms. elife 3:e04380
Nath RD, Chow ES, Wang H, Schwarz EM, Sternberg PW (2016) C. elegans stress-induced sleep emerges from the collective action of multiple neuropeptides. Curr Biol 26:2446–2455
Nathoo AN, Moeller RA, Westlund BA, Hart AC (2001) Identification of neuropeptide-like protein gene families in Caenorhabditis elegans and other species. Proc Natl Acad Sci U S A 98:14000–14005
Nelson SB, Valakh V (2015) Excitatory/inhibitory balance and circuit homeostasis in autism spectrum disorders. Neuron 87:684–698
Nelson MD, Trojanowski NF, George-Raizen JB, Smith CJ, Yu CC, Fang-Yen C, Raizen DM (2013) The neuropeptide NLP-22 regulates a sleep-like state in Caenorhabditis elegans. Nat Commun 4:2846
Ohtsuka K, Suzuki T (2000) Roles of molecular chaperones in the nervous system. Brain Res Bull 53:141–146
Petrash HA, Philbrook A, Haburcak M, Barbagallo B, Francis MM (2013) ACR-12 ionotropic acetylcholine receptor complexes regulate inhibitory motor neuron activity in Caenorhabditis elegans. J Neurosci Off J Soc Neurosci 33:5524–5532
Pettem KL, Yokomaku D, Luo L, Linhoff MW, Prasad T, Connor SA, Siddiqui TJ, Kawabe H, Chen F, Zhang L, Rudenko G, Wang YT, Brose N, Craig AM (2013) The specific alpha-neurexin interactor calsyntenin-3 promotes excitatory and inhibitory synapse development. Neuron 80:113–128
Pierce SB, Costa M, Wisotzkey R, Devadhar S, Homburger SA, Buchman AR, Ferguson KC, Heller J, Platt DM, Pasquinelli AA, Liu LX, Doberstein SK, Ruvkun G (2001) Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. Genes Dev 15:672–686
Qiu XB, Shao YM, Miao S, Wang L (2006) The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones. Cell Mol Life Sci 63:2560–2570
Rand JB (2007) Acetylcholine. WormBook 30:1–21
Reboul J, Vaglio P, Tzellas N, Thierry-Mieg N, Moore T, Jackson C, Shin-i T, Kohara Y, Thierry-Mieg D, Thierry-Mieg J, Lee H, Hitti J, Doucette-Stamm L, Hartley JL, Temple GF, Brasch MA, Vandenhaute J, Lamesch PE, Hill DE, Vidal M (2001) Open-reading-frame sequence tags (OSTs) support the existence of at least 17,300 genes in C. elegans. Nat Genet 27:332–336
Richmond JE, Jorgensen EM (1999) One GABA and two acetylcholine receptors function at the C. elegans neuromuscular junction. Nat Neurosci 2:791–797
Safdie G, Liewald JF, Kagan S, Battat E, Gottschalk A, Treinin M (2016) RIC-3 phosphorylation enables dual regulation of excitation and inhibition of Caenorhabditis elegans muscle. Mol Biol Cell 27:2994–3003
Sanes JR, Yamagata M (2009) Many paths to synaptic specificity. Annu Rev Cell Dev Biol 25:161–195
Sassa T, Murayama T, Maruyama IN (2013) Strongly alkaline pH avoidance mediated by ASH sensory neurons in C. elegans. Neurosci Lett 555:248–252
Seaton G, Hogg EL, Jo J, Whitcomb DJ, Cho K (2011) Sensing change: the emerging role of calcium sensors in neuronal disease. Semin Cell Dev Biol 22:530–535
Shapiro L, Love J, Colman DR (2007) Adhesion molecules in the nervous system: structural insights into function and diversity. Annu Rev Neurosci 30:451–474
Sheng L, Leshchyns’ka I, Sytnyk V (2013) Cell adhesion and intracellular calcium signaling in neurons. Cell Commun Signal 11:94
Sherman MY, Goldberg AL (2001) Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases. Neuron 29:15–32
Siddiqui TJ, Pancaroglu R, Kang Y, Rooyakkers A, Craig AM (2010) LRRTMs and neuroligins bind neurexins with a differential code to cooperate in glutamate synapse development. J Neurosci Off J Soc Neurosci 30:7495–7506
Stawicki TM, Takayanagi-Kiya S, Zhou K, Jin Y (2013) Neuropeptides function in a homeostatic manner to modulate excitation-inhibition imbalance in C. elegans. PLoS Genet 9:e1003472
Stitzel JA (2008) Naturally occurring genetic variability in the nicotinic acetylcholine receptor alpha4 and alpha7 subunit genes and phenotypic diversity in humans and mice. Front Biosci 13:477–491
Sudhof TC (2008) Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455:903–911
Takayanagi-Kiya S, Jin Y (2016) Altered function of the DnaJ family cochaperone DNJ-17 modulates locomotor circuit activity in a Caenorhabditis elegans seizure model. G3 (Bethesda) 6:2165–2171
Tessier-Lavigne M, Goodman CS (1996) The molecular biology of axon guidance. Science 274:1123–1133
Thapliyal S, Ravindranath S, Babu K (2018a) Regulation of glutamate signaling in the sensorimotor circuit by CASY-1A/calsyntenin in Caenorhabditis elegans. Genetics 208:1553–1564
Thapliyal S, Vasudevan A, Dong Y, Bai J, Koushika SP, Babu K (2018b) The C-terminal of CASY-1/Calsyntenin regulates GABAergic synaptic transmission at the Caenorhabditis elegans neuromuscular junction. PLoS Genet 14:e1007263
Togashi H, Abe K, Mizoguchi A, Takaoka K, Chisaka O, Takeichi M (2002) Cadherin regulates dendritic spine morphogenesis. Neuron 35:77–89
Togashi H, Miyoshi J, Honda T, Sakisaka T, Takai Y, Takeichi M (2006) Interneurite affinity is regulated by heterophilic nectin interactions in concert with the cadherin machinery. J Cell Biol 174:141–151
Togashi H, Sakisaka T, Takai Y (2009) Cell adhesion molecules in the central nervous system. Cell Adhes Migr 3:29–35
Touroutine D, Fox RM, Von Stetina SE, Burdina A, Miller DM III, Richmond JE (2005) acr-16 encodes an essential subunit of the levamisole-resistant nicotinic receptor at the Caenorhabditis elegans neuromuscular junction. J Biol Chem 280:27013–27021
Unwin N (2005) Refined structure of the nicotinic acetylcholine receptor at 4A resolution. J Mol Biol 346:967–989
Walsh FS, Doherty P (1997) Neural cell adhesion molecules of the immunoglobulin superfamily: role in axon growth and guidance. Annu Rev Cell Dev Biol 13:425–456
Ward S (1973) Chemotaxis by the nematode Caenorhabditis elegans: identification of attractants and analysis of the response by use of mutants. Proc Natl Acad Sci U S A 70:817–821
White JG, Southgate E, Thomson JN, Brenner S (1976) The structure of the ventral nerve cord of Caenorhabditis elegans. Philos Trans R Soc Lond Ser B Biol Sci 275:327–348
White JG, Southgate E, Thomson JN, Brenner S (1986) The structure of the nervous system of the nematode Caenorhabditis elegans. Philos Trans R Soc Lond Ser B Biol Sci 314:1–340
Yasuda S, Tanaka H, Sugiura H, Okamura K, Sakaguchi T, Tran U, Takemiya T, Mizoguchi A, Yagita Y, Sakurai T, De Robertis EM, Yamagata K (2007) Activity-induced protocadherin arcadlin regulates dendritic spine number by triggering N-cadherin endocytosis via TAO2beta and p38 MAP kinases. Neuron 56:456–471
Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O’Shea DJ, Sohal VS, Goshen I, Finkelstein J, Paz JT, Stehfest K, Fudim R, Ramakrishnan C, Huguenard JR, Hegemann P, Deisseroth K (2011) Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477:171–178
Zhou K, Cherra SJ III, Goncharov A, Jin Y (2017) Asynchronous cholinergic drive correlates with excitation-inhibition imbalance via a neuronal Ca2+ sensor protein. Cell Rep 19:1117–1129
Funding
ST was funded by the Council of Scientific and Industrial Research (CSIR) for a graduate fellowship. KB is an Intermediate Fellow of the Wellcome Trust- DBT India Alliance (Grant no. IA/I/12/1/500516) and thanks the Alliance for funding support.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Thapliyal, S., Babu, K. (2018). C. elegans Locomotion: Finding Balance in Imbalance. In: Chattopadhyay, K., Basu, S. (eds) Biochemical and Biophysical Roles of Cell Surface Molecules. Advances in Experimental Medicine and Biology, vol 1112. Springer, Singapore. https://doi.org/10.1007/978-981-13-3065-0_14
Download citation
DOI: https://doi.org/10.1007/978-981-13-3065-0_14
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-3064-3
Online ISBN: 978-981-13-3065-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)