Skip to main content
SpringerLink
Log in

Knockout of PINK1 altered the neural connectivity of Drosophila dopamine PPM3 neurons at input and output sites

  • Original Article
  • Published:
Invertebrate Neuroscience

Abstract

Impairment of the dopamine system is the main cause of Parkinson disease (PD). PTEN-induced kinase 1 (PINK1) is possibly involved in pathogenesis of PD. However, its role in dopaminergic neurons has not been fully established yet. In the present investigation, we have used the PINK1 knockout Drosophila model to explore the role of PINK1 in dopaminergic neurons. Electrophysiological and behavioral tests indicated that PINK1 elimination enhances the neural transmission from the presynaptic part of dopaminergic neurons in the protocerebral posterior medial region 3 (PPM3) to PPM3 neurons (which are homologous to those in the substantia nigra in humans). Firing properties of the action potential in PPM3 neurons were also altered in the PINK1 knockout genotypes. Abnormal motor ability was also observed in these PINK1 knockout animals. Our results indicate that knockout of PINK1 could alter both the input and output properties of PPM3 neurons.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Aarsland D, Creese B, Politis M, Chaudhuri KR, Ffytche DH et al (2017) Cognitive decline in Parkinson disease. Nat Rev Neurol 13:217–231

    Article  Google Scholar 

  • Aso Y, Hattori D, Yu Y, Johnston RM, Iyer NA et al (2014) The neuronal architecture of the mushroom body provides a logic for associative learning. eLife 3:e04577

    Article  Google Scholar 

  • Barone MC, Bohmann D (2013) Assessing neurodegenerative phenotypes in Drosophila dopaminergic neurons by climbing assays and whole brain immunostaining. J Vis Exp 74:e50339

    Google Scholar 

  • Cackovic J, Gutierrez-Luke S, Call GB, Juba A, O’Brien S et al (2018) Vulnerable Parkin loss-of-function drosophila dopaminergic neurons have advanced mitochondrial aging, mitochondrial network loss and transiently reduced autophagosome recruitment. Front Cell Neurosci 12:39

    Article  Google Scholar 

  • Clark IE, Dodson MW, Jiang CG, Cao JH, Huh JR et al (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441:1162–1166

    Article  CAS  Google Scholar 

  • Dickson DW, Braak H, Duda JE, Duyckaerts C, Gasser T et al (2009) Neuropathological assessment of Parkinson’s disease: refining the diagnostic criteria. Lancet Neurol 8:1150–1157

    Article  CAS  Google Scholar 

  • Exner N, Lutz AK, Haass C, Winklhofer KF (2012) Mitochondrial dysfunction in Parkinson’s disease: molecular mechanisms and pathophysiological consequences. EMBO J 31:3038–3062

    Article  CAS  Google Scholar 

  • Fricker D, Miles R (2000) EPSP amplification and the precision of spike timing in hippocampal neurons. Neuron 28:559–569

    Article  CAS  Google Scholar 

  • Gautier CA, Kitada T, Shen J (2008) Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proc Natl Acad Sci USA 105:11364–11369

    Article  CAS  Google Scholar 

  • Gouwens NW, Wilson RI (2009) Signal propagation in Drosophila central neurons. J Neurosci Off J Soc Neurosci 29:6239–6249

    Article  CAS  Google Scholar 

  • Gu HY, O’Dowd DK (2006) Cholinergic synaptic transmission in adult Drosophila kenyon cells in situ. J Neurosci 26:265–272

    Article  CAS  Google Scholar 

  • Guo M (2012) Drosophila as a model to study mitochondrial dysfunction in Parkinson’s disease. Csh Perspect Med 2:a009944

    Google Scholar 

  • Julienne H, Buhl E, Leslie DS, Hodge JJL (2017) Drosophila PINK1 and parkin loss-of-function mutants display a range of non-motor Parkinson’s disease phenotypes. Neurobiol Dis 104:15–23

    Article  CAS  Google Scholar 

  • Kitada T, Pisani A, Porter DR, Yamaguchi H, Tscherter A et al (2007) Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice. Proc Natl Acad Sci USA 104:11441–11446

    Article  CAS  Google Scholar 

  • Kong EC, Woo K, Li H, Lebestky T, Mayer N et al (2010) A pair of dopamine neurons target the D1-like dopamine receptor DopR in the central complex to promote ethanol-stimulated locomotion in Drosophila. PLoS ONE 5:9954

    Article  Google Scholar 

  • Lang AE, Espay AJ (2018) Disease modification in Parkinson’s disease: current approaches, challenges, and future considerations. Mov Disord 33:660–677

    Article  Google Scholar 

  • Lee KS, Huh S, Lee S, Wu ZH, Kim AK et al (2018) Altered ER-mitochondria contact impacts mitochondria calcium homeostasis and contributes to neurodegeneration in vivo in disease models. Proc Natl Acad Sci USA 115:E8844–E8853

    Article  CAS  Google Scholar 

  • Madeo G, Schirinzi T, Maltese M, Martella G, Rapino C et al (2016) Dopamine-dependent CB1 receptor dysfunction at corticostriatal synapses in homozygous PINK1 knockout mice. Neuropharmacology 101:460–470

    Article  CAS  Google Scholar 

  • Mao Z, Davis RL (2009) Eight different types of dopaminergic neurons innervate the Drosophila mushroom body neuropil: anatomical and physiological heterogeneity. Front Neural Circuits 3:5

    Article  Google Scholar 

  • Massano J, Bhatia KP (2012) Clinical approach to parkinson’s disease: features, diagnosis, and principles of management. Csh Perspect Med 2:a008870

    Google Scholar 

  • Matsuda S, Kitagishi Y, Kobayashi M (2013) Function and characteristics of PINK1 in mitochondria. Oxid Med Cell Longev 2013:601587

    Article  Google Scholar 

  • Michel PP, Hirsch EC, Hunot S (2016) Understanding dopaminergic cell death pathways in Parkinson disease. Neuron 90:675–691

    Article  CAS  Google Scholar 

  • Midorikawa M, Sakaba T (2017) Kinetics of releasable synaptic vesicles and their plastic changes at hippocampal mossy fiber synapses. Neuron 96(1033–1040):e1033

    Article  Google Scholar 

  • Mouton-Ligeri F, Jacoupy M, Corvol JC, Corti O (2017) PINK1/Parkin-dependent mitochondrial surveillance: from pleiotropy to Parkinson’s disease. Front Mol Neurosci 10:120

    Article  Google Scholar 

  • Nissim TBK, Zhang XX, Elazar A, Roy S, Stolwijk JA et al (2017) Mitochondria control store-operated Ca2 + entry through Na + and redox signals. EMBO J 36:797–815

    Article  Google Scholar 

  • Nita I, Hershfinkel M, Fishman D, Ozeri E, Rutter GA et al (2012) The mitochondrial Na +/Ca2 + exchanger upregulates glucose dependent Ca2 + signalling linked to insulin secretion. PLoS ONE 7:e46649

    Article  CAS  Google Scholar 

  • Nita II, Hershfinkel M, Lewis EC, Sekler I (2015) A crosstalk between Na + channels, Na +/K + pump and mitochondrial Na + transporters controls glucose-dependent cytosolic and mitochondrial Na + signals. Cell Calcium 57:69–75

    Article  CAS  Google Scholar 

  • Otani S, Daniel H, Roisin MP, Crepel F (2003) Dopaminergic modulation of long-term synaptic plasticity in rat prefrontal neurons. Cereb Cortex 13:1251–1256

    Article  Google Scholar 

  • Parker WD, Parks JK, Swerdlow RH (2008) Complex I deficiency in Parkinson’s disease frontal cortex. Brain Res 1189:215–218

    Article  CAS  Google Scholar 

  • Pfeiffer K, Homberg U (2014) Organization and functional roles of the central complex in the insect brain. Annu Rev Entomol 59:165-U787

    Article  Google Scholar 

  • Pickrell AM, Youle RJ (2015) The roles of PINK1, Parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron 85:257–273

    Article  CAS  Google Scholar 

  • Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P et al (2017) Parkinson disease. Nat Rev Dis Prim 3:1–21

    Google Scholar 

  • Qiao J, Zou X, Lai D, Yan Y, Wang Q et al (2014) Azadirachtin blocks the calcium channel and modulates the cholinergic miniature synaptic current in the central nervous system of Drosophila. Pest Manag Sci 70:1041–1047

    Article  CAS  Google Scholar 

  • Rodriguez-Oroz MC, Jahanshahi M, Krack P, Litvan I, Macias R et al (2009) Initial clinical manifestations of Parkinson’s disease: features and pathophysiological mechanisms. Lancet Neurol 8:1128–1139

    Article  CAS  Google Scholar 

  • Schapira AH, Cooper JM, Dexter D, Jenner P, Clark JB et al (1989) Mitochondrial complex I deficiency in Parkinson’s disease. Lancet 1:1269

    Article  CAS  Google Scholar 

  • Spruston N, Jaffe DB, Williams SH, Johnston D (1993) Voltage- and space-clamp errors associated with the measurement of electronically remote synaptic events. J Neurophysiol 70:781–802

    Article  CAS  Google Scholar 

  • Strausfeld NJ, Hirth F (2013) Deep homology of arthropod central complex and vertebrate basal ganglia. Science 340:157–161

    Article  CAS  Google Scholar 

  • Villeneuve LM, Purnell PR, Boska MD, Fox HS (2016) Early expression of Parkinson’s disease-related mitochondrial abnormalities in PINK1 knockout rats. Mol Neurobiol 53:171–186

    Article  CAS  Google Scholar 

  • Wang HL, Chou AH, Wu AS, Chen SY, Weng YH et al (2011) PARK6 PINK1 mutants are defective in maintaining mitochondrial membrane potential and inhibiting ROS formation of substantia nigra dopaminergic neurons. Biochim Biophys Acta 1812:674–684

    Article  CAS  Google Scholar 

  • Zhu GQ, Liu Y, Wang YB, Bi XN, Baudry M (2015) Different patterns of electrical activity lead to long-term potentiation by activating different intracellular pathways. J Neurosci 35:621–633

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported by National Nature Science Foundation of China, Grant Number: 81701414.

Author information

Authors and Affiliations

  1. Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China

    Jing-Da Qiao

  2. Center for Reproductive Medicine, the Third Affiliated Hospital of Guangzhou Medical University; Key Laboratory for Reproductive Medicine of Guangdong; Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes; and Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, People’s Republic of China

    Yu-Ling Mao

Authors
  1. Jing-Da Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu-Ling Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yu-Ling Mao.

Ethics declarations

Conflict of interest

None.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 67 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qiao, JD., Mao, YL. Knockout of PINK1 altered the neural connectivity of Drosophila dopamine PPM3 neurons at input and output sites. Invert Neurosci 20, 11 (2020). https://doi.org/10.1007/s10158-020-00244-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10158-020-00244-4

Keywords

Search

Navigation