A new method of recording from the giant fiber of Drosophila melanogaster shows that the strength of its auditory inputs remains constant with age
Autoři:
Jonathan M. Blagburn aff001
Působiště autorů:
Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan, PR, United States of America
aff001
Vyšlo v časopise:
PLoS ONE 15(1)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0224057
Souhrn
There have been relatively few studies of how central synapses age in adult Drosophila melanogaster. In this study we investigate the aging of the synaptic inputs to the Giant Fiber (GF) from auditory Johnston’s Organ neurons (JONs). In previously published experiments an indirect assay of this synaptic connection was used; here we describe a new, more direct assay, which allows reliable detection of the GF action potential in the neck connective, and long term recording of its responses to sound. Genetic poisoning using diphtheria toxin expressed in the GF with R68A06-GAL4 was used to confirm that this signal indeed arose from the GF and not from other descending neurons. As before, the sound-evoked action potentials (SEPs) in the antennal nerve were recorded via an electrode inserted at the base of the antenna. It was noted that an action potential in the GF elicited an antennal twitch, which in turn evoked a mechanosensory response from the JONs in the absence of sound. We then used these extracellular recording techniques in males and female of different ages to quantify the response of the JONs to a brief sound impulse, and also to measure the strength of the connection between the JONs and the GF. At no age was there any significant difference between males and females, for any of the parameters measured. The sensitivity of the JONs to a sound impulse approximately doubled between 1 d and 10 d after eclosion, which corresponds to the period when most mating is taking place. Subsequently JON sensitivity decreased with age, being approximately half as sensitive at 20 d and one-third as sensitive at 50 d, as compared to 10 d. However, the strength of the connection between the auditory input and the GF itself remained unchanged with age, although it did show some variability that could mask any small changes.
Klíčová slova:
Action potentials – Drosophila melanogaster – Electrode potentials – Eyes – Functional electrical stimulation – Neuronal dendrites – Neurons – Synapses
Zdroje
1. Mostany R, Anstey JE, Crump KL, Maco B, Knott G, Portera-Cailliau C. Altered Synaptic Dynamics during Normal Brain Aging. J Neurosci. 2013;33: 4094–4104. doi: 10.1523/JNEUROSCI.4825-12.2013 23447617
2. Masliah E, Mallory M, Hansen L, DeTeresa R, Terry RD. Quantitative synaptic alterations in the human neocortex during normal aging. Neurology. 1993;43: 192–7. doi: 10.1212/wnl.43.1_part_1.192 8423884
3. Petralia RS, Mattson MP, Yao PJ. Communication breakdown: The impact of ageing on synapse structure. Ageing Res Rev. 2014;14: 31–42. doi: 10.1016/j.arr.2014.01.003 24495392
4. Graham LC, Naldrett MJ, Kohama SG, Smith C, Lamont DJ, McColl BW, et al. Regional Molecular Mapping of Primate Synapses during Normal Healthy Aging. Cell Rep. 2019;27: 1018–1026.e4. doi: 10.1016/j.celrep.2019.03.096 31018120
5. Rozycka A, Liguz-Lecznar M. The space where aging acts: focus on the GABAergic synapse. Aging Cell. 2017;16: 634–643. doi: 10.1111/acel.12605 28497576
6. Peters A, Sethares C, Luebke JI. Synapses are lost during aging in the primate prefrontal cortex. Neuroscience. 2008;152: 970–981. doi: 10.1016/j.neuroscience.2007.07.014 18329176
7. Barnes CA. Normal aging: regionally specific changes in hippocampal synaptic transmission. Trends Neurosci. 1994;17: 13–8. Available: http://www.ncbi.nlm.nih.gov/pubmed/7511843 doi: 10.1016/0166-2236(94)90029-9 7511843
8. Azpurua J, Eaton BA. Neuronal epigenetics and the aging synapse. Front Cell Neurosci. 2015;9: 208. doi: 10.3389/fncel.2015.00208 26074775
9. Huttenlocher PR. Synaptic density in human frontal cortex—Developmental changes and effects of aging. Brain Res. 1979;163: 195–205. doi: 10.1016/0006-8993(79)90349-4 427544
10. Beramendi A, Peron S, Casanova G, Reggiani C, Cantera R. Neuromuscular junction in abdominal muscles of Drosophila melanogaster during adulthood and aging. J Comp Neurol. 2007;501: 498–508. doi: 10.1002/cne.21253 17278125
11. Mahoney RE, Rawson JM, Eaton BA. An Age-Dependent Change in the Set Point of Synaptic Homeostasis. J Neurosci. 2014;34: 2111–2119. doi: 10.1523/JNEUROSCI.3556-13.2014 24501352
12. Azpurua J, Mahoney RE, Eaton BA. Transcriptomics of aged Drosophila motor neurons reveals a matrix metalloproteinase that impairs motor function. Aging Cell. 2018;17: e12729. doi: 10.1111/acel.12729 29411505
13. Haddadi M, Jahromi SR, Sagar BKC, Patil RK, Shivanandappa T, Ramesh SR. Brain aging, memory impairment and oxidative stress: A study in Drosophila melanogaster. Behav Brain Res. 2014;259: 60–69. doi: 10.1016/j.bbr.2013.10.036 24183945
14. Gupta VK, Pech U, Bhukel A, Fulterer A, Ender A, Mauermann SF, et al. Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release. Tissenbaum HA, editor. PLOS Biol. 2016;14: e1002563. doi: 10.1371/journal.pbio.1002563 27684064
15. Augustin H, McGourty K, Allen MJ, Madem SK, Adcott J, Kerr F, et al. Reduced insulin signaling maintains electrical transmission in a neural circuit in aging flies. Murphy C, editor. PLOS Biol. 2017;15: e2001655. doi: 10.1371/journal.pbio.2001655 28902870
16. Blagburn JM, Alexopoulos H, Davies JA, Bacon JP. Null mutation in shaking-B eliminates electrical, but not chemical, synapses in the Drosophila giant fiber system: a structural study. J Comp Neurol. 1999;404: 449–458. doi: 10.1002/(SICI)1096-9861(19990222)404:4<449::AID-CNE3>3.0.CO;2-D 9987990
17. Allen MJ, Murphey RK. The chemical component of the mixed GF-TTMn synapse in Drosophila melanogaster uses acetylcholine as its neurotransmitter. Eur J Neurosci. 2007;26: 439–445. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17650116 doi: 10.1111/j.1460-9568.2007.05686.x 17650116
18. Phelan P, Goulding LA, Tam JLY, Allen MJ, Dawber RJ, Davies JA, et al. Molecular mechanism of rectification at identified electrical synapses in the Drosophila giant fiber system. Curr Biol. 2008;18: 1955–60. doi: 10.1016/j.cub.2008.10.067 19084406
19. Phelan P, Nakagawa M, Wilkin MB, Moffat KG, O’Kane CJ, Davies JA, et al. Mutations in shaking-B prevent electrical synapse formation in the Drosophila giant fiber system. J Neurosci. 1996;16: 1101–1113. Available: http://www.ncbi.nlm.nih.gov/pubmed/8558239 doi: 10.1523/JNEUROSCI.16-03-01101.1996 8558239
20. King DG, Wyman RJ. Anatomy of the giant fibre pathway in Drosophila. I. Three thoracic components of the pathway. J Neurocytol. 1980;9: 753–770. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6782199 doi: 10.1007/bf01205017 6782199
21. Koto M, Tanouye MA, Ferrus A, Thomas JB, Wyman RJ. The morphology of the cervical giant fiber neuron of Drosophila. Brain Res. 1981;221: 213–217. Available: http://www.ncbi.nlm.nih.gov/pubmed/6793208 doi: 10.1016/0006-8993(81)90772-1 6793208
22. von Reyn CR, Breads P, Peek MY, Zheng GZ, Williamson WR, Yee AL, et al. A spike-timing mechanism for action selection. Nat Neurosci. 2014;17: 962–70. doi: 10.1038/nn.3741 24908103
23. Card GM. Escape behaviors in insects. Curr Opin Neurobiol. 2012;22: 180–6. doi: 10.1016/j.conb.2011.12.009 22226514
24. von Reyn CR, Nern A, Williamson WR, Breads P, Wu M, Namiki S, et al. Feature Integration Drives Probabilistic Behavior in the Drosophila Escape Response. Neuron. 2017;94: 1190–1204.e6. doi: 10.1016/j.neuron.2017.05.036 28641115
25. Hammond S, O’Shea M. Escape flight initiation in the fly. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2007;193: 471–476. doi: 10.1007/s00359-006-0203-9 17221263
26. Fotowat H, Fayyazuddin A, Bellen HJ, Gabbiani F. A novel neuronal pathway for visually guided escape in Drosophila melanogaster. J Neurophysiol. 2009;102: 875–885. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19474177 doi: 10.1152/jn.00073.2009 19474177
27. Boekhoff-Falk G, Eberl DF. The Drosophila auditory system. Wiley Interdiscip Rev Dev Biol. 2014;3: 179–91. doi: 10.1002/wdev.128 24719289
28. Pézier A, Jezzini SH, Marie B, Blagburn JM. Engrailed alters the specificity of synaptic connections of Drosophila auditory neurons with the giant fiber. J Neurosci. 2014;34. doi: 10.1523/JNEUROSCI.1939-14.2014 25164665
29. Pézier AP, Jezzini SH, Bacon JP, Blagburn JM. Shaking B mediates synaptic coupling between auditory sensory neurons and the giant fiber of Drosophila melanogaster. PLoS One. 2016;11. doi: 10.1371/journal.pone.0152211 27043822
30. Lehnert BP, Baker AE, Gaudry Q, Chiang A-S, Wilson RI. Distinct Roles of TRP Channels in Auditory Transduction and Amplification in Drosophila. Neuron. Elsevier Inc.; 2013;77: 115–128. doi: 10.1016/j.neuron.2012.11.030 23312520
31. Pézier A, Blagburn JM. Auditory responses of engrailed and invected-expressing Johnston’s Organ neurons in Drosophila melanogaster. PLoS One. 2013;8: e71419. doi: 10.1371/journal.pone.0071419 23940751
32. Allen MJ, Godenschwege TA, Tanouye MA, Phelan P. Making an escape: development and function of the Drosophila giant fibre system. Semin Cell Dev Biol. 2006;17: 31–41. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16378740 doi: 10.1016/j.semcdb.2005.11.011 16378740
33. Tootoonian S, Coen P, Kawai R, Murthy M. Neural Representations of Courtship Song in the Drosophila Brain. J Neurosci. 2012;32: 787–798. doi: 10.1523/JNEUROSCI.5104-11.2012 22262877
34. Eberl DF, Hardy RW, Kernan MJ. Genetically similar transduction mechanisms for touch and hearing in Drosophila. J Neurosci. 2000;20: 5981–5988. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10934246 doi: 10.1523/JNEUROSCI.20-16-05981.2000 10934246
35. Ishikawa Y, Okamoto N, Nakamura M, Kim H, Kamikouchi A. Anatomic and Physiologic Heterogeneity of Subgroup-A Auditory Sensory Neurons in Fruit Flies. Front Neural Circuits. 2017;11: 46. doi: 10.3389/fncir.2017.00046 28701929
36. Bennet-Clark HC, Ewing AW. Stimuli provided by courtship of male Drosophila melanogaster [62]. Nature. 1967. pp. 669–671. doi: 10.1038/213669a0
37. Bennet-Clark HC, Ewing AW. Pulse interval as a critical parameter in the courtship song of Drosophila melanogaster. Anim Behav. 1969;17: 755–759. doi: 10.1016/S0003-3472(69)80023-0
38. von Schilcher F. The role of auditory stimuli in the courtship of Drosophila melanogaster. Anim Behav. 1976;24: 18–26. doi: 10.1016/S0003-3472(76)80095-4
39. Deutsch D, Clemens J, Thiberge SY, Guan G, Murthy M. Shared Song Detector Neurons in Drosophila Male and Female Brains Drive Sex-Specific Behaviors. Curr Biol. Cell Press; 2019;29: 3200–3215.e5. doi: 10.1016/j.cub.2019.08.008 31564492
40. Makhijani K, Alexander B, Tanaka T, Rulifson E, Brückner K. The peripheral nervous system supports blood cell homing and survival in the Drosophila larva. Development. 2011;138: 5379–91. doi: 10.1242/dev.067322 22071105
41. Allen MJ, Godenschwege TA. Electrophysiological recordings from the Drosophila Giant Fiber System (GFS). Cold Spring Harb Protoc. 2010;2010: pdb.prot5453. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20647357
42. Eberl DF, Kernan MJ. Recording sound-evoked potentials from the Drosophila antennal nerve. Cold Spring Harb Protoc. 2011; prot5576. doi: 10.1101/pdb.prot5576 21363940
43. Patella P, Wilson RI. Functional Maps of Mechanosensory Features in the Drosophila Brain. Curr Biol. 2018;28: 1189–1203.e5. doi: 10.1016/j.cub.2018.02.074 29657118
44. Bacon JP, Strausfeld NJ. The dipteran ‘ Giant fibre’ pathway: neurons and signals. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 1986;158: 529–548.
45. Tanouye MA, Wyman RJ. Motor outputs of giant nerve fiber in Drosophila. J Neurophysiol. 1980;44: 405–421. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6774064 doi: 10.1152/jn.1980.44.2.405 6774064
46. Levine JD, Tracey D. Structure and function of the giant motorneuron of Drosophila melanogaster. J Comp Physiol. 1973;87: 213–235.
47. Trimarchi JR, Schneiderman A M. Giant fiber activation of an intrinsic muscle in the mesothoracic leg of Drosophila melanogaster. J Exp Biol. 1993;177: 149–67. Available: http://www.ncbi.nlm.nih.gov/pubmed/8486998 8486998
48. Hammer Ø, Harper DAT, Ryan PD. Paleontological statistics software package for education and data analysis. Palaeontol Electron. 2001;4: 9pp.
49. Pitnick S. Investment in Testes and the Cost of Making Long Sperm in Drosophila. Am Nat. University of Chicago Press; 1996;148: 57–80. doi: 10.1086/285911
50. Fricke C, Green D, Mills WE, Chapman T. Age-dependent female responses to a male ejaculate signal alter demographic opportunities for selection. Proceedings Biol Sci. The Royal Society; 2013;280: 20130428. doi: 10.1098/rspb.2013.0428 23843383
51. Miller PB, Obrik-Uloho OT, Phan MH, Medrano CL, Renier JS, Thayer JL, et al. The song of the old mother: reproductive senescence in female drosophila. Fly (Austin). Taylor & Francis; 2014;8: 127–39. doi: 10.4161/19336934.2014.969144 25523082
52. Ruhmann H, Wensing KU, Neuhalfen N, Specker J-H, Fricke C. Early reproductive success in Drosophila males is dependent on maturity of the accessory gland. Behav Ecol. Narnia; 2016;27: arw123. doi: 10.1093/beheco/arw123
53. Ruhmann H, Koppik M, Wolfner MF, Fricke C. The impact of ageing on male reproductive success in Drosophila melanogaster. Exp Gerontol. NIH Public Access; 2018;103: 1. doi: 10.1016/j.exger.2017.12.013 29258876
54. Fayyazuddin A, Zaheer MA, Hiesinger PR, Bellen HJ. The nicotinic acetylcholine receptor Dalpha7 is required for an escape behavior in Drosophila. PLoS Biol. 2006;4: e63. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16494528 doi: 10.1371/journal.pbio.0040063 16494528
55. Murphey RK, Bacon JP, Sakaguchi DS, Johnson SE. Transplantation of cricket sensory neurons to ectopic locations: arborizations and synaptic connections. J Neurosci. 1983;3: 659–672. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6834102 doi: 10.1523/JNEUROSCI.03-04-00659.1983 6834102
56. Orr BO, Borgen MA, Caruccio PM, Murphey RK. Netrin and frazzled regulate presynaptic gap junctions at a Drosophila giant synapse. J Neurosci. 2014;34: 5416–30. doi: 10.1523/JNEUROSCI.3183-13.2014 24741033
57. Kadas D, Duch C, Consoulas C. Postnatal Increases in Axonal Conduction Velocity of an Identified Drosophila Interneuron Require Fast Sodium, L-Type Calcium and Shaker Potassium Channels. eneuro. 2019;6: ENEURO.0181-19.2019. doi: 10.1523/ENEURO.0181-19.2019 31253715
58. Lehnert BP, Baker AE, Gaudry Q, Chiang A-S, Wilson RI. Supplemental Information. Distinct Roles of TRP Channels in Auditory Transduction and Amplification in Drosophila. Neuron. 2013;77.
59. Mu L, Bacon JP, Ito K, Strausfeld NJ. Responses of Drosophila giant descending neurons to visual and mechanical stimuli. J Exp Biol. 2014;217: 2121–2129. doi: 10.1242/jeb.099135 24675562
60. Ache JM, Polsky J, Alghailani S, Parekh R, Breads P, Peek MY, et al. Neural Basis for Looming Size and Velocity Encoding in the Drosophila Giant Fiber Escape Pathway. Curr Biol. 2019;29: 1073–1081.e4. doi: 10.1016/j.cub.2019.01.079 30827912
61. Mu L, Ito K, Bacon JP, Strausfeld NJ. Optic glomeruli and their inputs in Drosophila share an organizational ground pattern with the antennal lobes. J Neurosci. 2012;32: 6061–71. doi: 10.1523/JNEUROSCI.0221-12.2012 22553013
62. Gold C, Henze DA, Koch C, Buzsáki G. On the Origin of the Extracellular Action Potential Waveform: A Modeling Study. J Neurophysiol. 2006;95: 3113–3128. doi: 10.1152/jn.00979.2005 16467426
63. Tanouye M A, Ferrus A, Fujita SC. Abnormal action potentials associated with the Shaker complex locus of Drosophila. Proc Natl Acad Sci U S A. 1981;78: 6548–52. Available: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=349078&tool=pmcentrez&rendertype=abstract doi: 10.1073/pnas.78.10.6548 16593105
64. Thomas JB, Wyman RJ. Mutations altering synaptic connectivity between identified neurons in Drosophila. J Neurosci. 1984;4: 530–538. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6699687 doi: 10.1523/JNEUROSCI.04-02-00530.1984 6699687
65. Thum AS, Knapek S, Rister J, Dierichs-schmitt E, Heisenberg M, Tanimoto H. Differential potencies of effector genes in adult Drosophila. J Comp Neurol. 2006;498: 194–203. doi: 10.1002/cne.21022 16856137
66. Robie AA, Hirokawa J, Edwards AW, Umayam LA, Lee A, Phillips ML, et al. Mapping the Neural Substrates of Behavior. Cell. 2017;170: 393–406.e28. doi: 10.1016/j.cell.2017.06.032 28709004
67. Kudumala SR, Penserga T, Börner J, Slipchuk O, Kakad P, Lee LH, et al. Lissencephaly-1 dependent axonal retrograde transport of L1-type CAM Neuroglian in the adult drosophila central nervous system. Brembs B, editor. PLoS One. Public Library of Science; 2017;12: e0183605. doi: 10.1371/journal.pone.0183605 28837701
68. Mamiya A, Straw AD, Tómasson E, Dickinson MH. Active and passive antennal movements during visually guided steering in flying Drosophila. J Neurosci. Society for Neuroscience; 2011;31: 6900–14. doi: 10.1523/JNEUROSCI.0498-11.2011 21543620
69. Jezzini SH, Merced A, Blagburn JM. Shaking-B misexpression increases the formation of gap junctions but not chemical synapses between auditory sensory neurons and the giant fiber of Drosophila melanogaster. PLoS One. Public Library of Science; 2018;13. doi: 10.1371/journal.pone.0198710 30118493
70. Sivan-Loukianova E, Eberl DF. Synaptic ultrastructure of Drosophila Johnston’s organ axon terminals as revealed by an enhancer trap. J Comp Neurol. 2005;491: 46–55. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16127697 doi: 10.1002/cne.20687 16127697
71. Yorozu S, Wong A, Fischer BJ, Dankert H, Kernan MJ, Kamikouchi A, et al. Distinct sensory representations of wind and near-field sound in the Drosophila brain. Nature. 2009;458: 201–5. doi: 10.1038/nature07843 19279637
72. Kamikouchi A, Inagaki HK, Effertz T, Hendrich O, Fiala A, Gopfert MC, et al. The neural basis of Drosophila gravity-sensing and hearing. Nature. 2009;458: 165–171. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19279630 doi: 10.1038/nature07810 19279630
73. Alvarez-Castelao B, Schuman EM. The regulation of synaptic protein turnover. Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology Inc.; 2015. pp. 28623–28630. doi: 10.1074/jbc.R115.657130 26453306
74. Hobert O. Regulatory logic of neuronal diversity: terminal selector genes and selector motifs. Proc Natl Acad Sci U S A. 2008;105: 20067–71. doi: 10.1073/pnas.0806070105 19104055
75. Hobert O, Kratsios P. Neuronal identity control by terminal selectors in worms, flies, and chordates. Curr Opin Neurobiol. 2019;56: 97–105. doi: 10.1016/j.conb.2018.12.006 30665084
76. Masoudi N, Tavazoie S, Glenwinkel L, Ryu L, Kim K, Hobert O. Unconventional function of an Achaete-Scute homolog as a terminal selector of nociceptive neuron identity. PLoS Biol. Public Library of Science; 2018;16. doi: 10.1371/journal.pbio.2004979 29672507
77. Leyva-Díaz E, Hobert O. Transcription factor autoregulation is required for acquisition and maintenance of neuronal identity. Development. 2019;146. doi: 10.1242/dev.177378 31227642
78. Marie B, Cruz-Orengo L, Blagburn JM. Persistent engrailed expression is required to determine sensory axon trajectory, branching, and target choice. J Neurosci. 2002;22: 832–841. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11826113 doi: 10.1523/JNEUROSCI.22-03-00832.2002 11826113
79. Booth D, Marie B, Domenici P, Blagburn JM, Bacon JP. Transcriptional control of behavior: engrailed knock-out changes cockroach escape trajectories. J Neurosci. 2009;29: 7181–7190. doi: 10.1523/JNEUROSCI.1374-09.2009 19494140
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