Skip to main content

Role of Spontaneous Activity in the Maturation of GABAergic Synapses in Embryonic Spinal Circuits

  • Chapter
  • First Online:

Abstract

Spontaneous network activity (SNA) is displayed in many developing neural circuits shortly after synaptic connections form, and this activity is thought to be important for the maturation of the synaptic networks in which it is expressed. This chapter discusses the relationship between GABAergic signaling and SNA in the embryonic spinal cord. Spinal SNA consists of episodic bursts of spiking activity followed by quiescent periods. Episodes occur as a result of the highly excitable nature of these embryonic circuits. One of the important contributors to the excitable state of these developing networks is the depolarizing excitatory nature of GABAergic neurotransmission. This is due to high intracellular chloride levels in embryonic neurons, which set the GABAergic reversal potential (EGABA) to a level more depolarized than the resting potential. Recently, we have shown that SNA plays a role in adjusting the strength of immature spinal synapses through a general mechanism known as homeostatic plasticity. We propose that levels of SNA are homeostatically maintained through compensatory changes in synaptic strength. We find that the entire distribution of GABAergic miniature postsynaptic current (mPSC) amplitudes are increased by a multiplicative factor (scaled) after chronic blockade of SNA. We also have evidence that the scaling process is mediated by an increase in chloride accumulation.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Akerman CJ, Cline HT (2007) Refining the roles of GABAergic signaling during neural circuit formation. Trends Neurosci 30:382–389

    Article  CAS  PubMed  Google Scholar 

  • Abbott LF, and Nelson SB (2000) Synaptic plasticity: taming the beast. Nat Neurosci 3 Suppl, 1178–1183

    Article  CAS  PubMed  Google Scholar 

  • Bekoff A, Stein P, Hamburger V (1975) Coordinated motor output in the hindlimb of the 7-day chick embryo. Proc Natl Acad Sci USA 72:1245–1248

    Article  CAS  PubMed  Google Scholar 

  • Ben-Ari Y, Gaiarsa JL, Tyzio R, Khazipov R (2007) GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev 87:1215–1284

    Article  CAS  PubMed  Google Scholar 

  • Bliss TV, and Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 232: 331–356

    Article  CAS  PubMed  Google Scholar 

  • Burrone J, Murthy VN (2003) Synaptic gain control and homeostasis. Curr Opin Neurobiol 13:560–567

    Article  CAS  PubMed  Google Scholar 

  • Chub N, O’Donovan MJ (1998) Blockade and recovery of spontaneous rhythmic activity after application of neurotransmitter antagonists to spinal networks of the chick embryo. J Neurosci 18:294–306

    CAS  PubMed  Google Scholar 

  • Chub N, O’Donovan MJ (2001) Post-episode depression of GABAergic transmission in spinal neurons of the chick embryo. J Neurophysiol 85:2166–2176

    CAS  PubMed  Google Scholar 

  • Chub N, Mentis GZ, O’Donovan MJ (2006) Chloride-sensitive MEQ fluorescence in chick embryo motoneurons following manipulations of chloride and during spontaneous network activity. J Neurophysiol 95:323–330

    Article  CAS  PubMed  Google Scholar 

  • Cline HT (1991) Activity-dependent plasticity in the visual systems of frogs and fish. Trends Neurosci 14:104–111

    Article  CAS  PubMed  Google Scholar 

  • Davis GW (2006) Homeostatic control of neural activity: from phenomenology to molecular design. Annu Rev Neurosci 29:307–323

    Article  CAS  PubMed  Google Scholar 

  • Fedirchuk B, Wenner P, Whelan PJ, Ho S, Tabak J, O’Donovan MJ (1999) Spontaneous network activity transiently depresses synaptic transmission in the embryonic chick spinal cord. J Neurosci 19:2102–2112

    CAS  PubMed  Google Scholar 

  • Feller MB (1999) Spontaneous correlated activity in developing neural circuits. Neuron 22:653–656

    Article  CAS  PubMed  Google Scholar 

  • Ge S, Goh EL, Sailor KA, Kitabatake Y, Ming GL, Song H (2006) GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439:589–593

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez-Islas CE, Wenner P (2006) Spontaneous network activity in the embryonic spinal cord regulates AMPAergic and GABAergic synaptic strength. Neuron 49:563–575

    Article  CAS  PubMed  Google Scholar 

  • Gu X, Spitzer NC (1997) Breaking the code: regulation of neuronal differentiation by spontaneous calcium transients. Dev Neurosci 19:33–41

    Article  CAS  PubMed  Google Scholar 

  • Hall BK, Herring SW (1990) Paralysis and growth of the musculoskeletal system in the embryonic chick. J Morphol 206:45–56

    Article  CAS  PubMed  Google Scholar 

  • Hamburger V (1977) The developmental history of the motor neuron. Neurosci Res Program Bull 15:1–37

    Google Scholar 

  • Hanson MG, Landmesser LT (2004) Normal patterns of spontaneous activity are required for correct motor axon guidance and the expression of specific guidance molecules. Neuron 43:687–701

    Article  CAS  PubMed  Google Scholar 

  • Hanson MG, Milner LD, Landmesser LT (2008) Spontaneous rhythmic activity in early chick spinal cord influences distinct motor axon pathfinding decisions. Brain Res Rev 57:77–85

    Article  PubMed  Google Scholar 

  • Hawkins RD, Kandel ER, and Siegelbaum SA (1993) Learning to modulate transmitter release: themes and variations in synaptic plasticity. Annu Rev Neurosci 16:625–665

    Article  PubMed  Google Scholar 

  • Jarvis C, Sutherland H, Mayne CN, Gilroy SJ, Salmons S (1996) Induction of a fast-oxidative phenotype by chronic muscle stimulation: mechanical and biochemical studies. Am J Physiol 270:C306–C312

    CAS  PubMed  Google Scholar 

  • Kandler K, Gillespie DC (2005) Developmental refinement of inhibitory sound-localization circuits. Trends Neurosci 28:290–296

    Article  CAS  PubMed  Google Scholar 

  • Katz LC, Shatz CJ (1996) Synaptic activity and the construction of cortical circuits. Science 274:1133–1138

    Article  CAS  PubMed  Google Scholar 

  • Kilman V, van Rossum MC, Turrigiano GG (2002) Activity deprivation reduces miniature IPSC amplitude by decreasing the number of postsynaptic GABA(A) receptors clustered at neocortical synapses. J Neurosci 22:1328–1337

    CAS  PubMed  Google Scholar 

  • LeMasson G, Marder E, Abbott LF (1993) Activity-dependent regulation of conductances in model neurons. Science 259:1915–1917

    Article  CAS  PubMed  Google Scholar 

  • Linden DJ, and Connor JA (1995) Long-term synaptic depression. Annu Rev Neurosci 18:319–357

    Article  CAS  PubMed  Google Scholar 

  • Lissin DV, Gomperts SN, Carroll RC, Christine CW, Kalman D, Kitamura M, Hardy S, Nicoll RA, Malenka RC, von Zastrow M (1998) Activity differentially regulates the surface expression of synaptic AMPA and NMDA glutamate receptors. Proc Natl Acad Sci USA 95:7097–7102

    Article  CAS  PubMed  Google Scholar 

  • Malenka RC, and Nicoll RA (1993) NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms. Trends Neurosci 16:521–527

    Article  CAS  PubMed  Google Scholar 

  • Malenka RC, Nicoll RA (1999) Long-term potentiation–a decade of progress? Science 285:1870–1874

    Article  CAS  PubMed  Google Scholar 

  • Marchetti C, Tabak J, Chub N, O’Donovan MJ, Rinzel J (2005) Modeling spontaneous activity in the developing spinal cord using activity-dependent variations of intracellular chloride. J Neurosci 25:3601–3612

    Article  CAS  PubMed  Google Scholar 

  • Marder E, Goaillard JM (2006) Variability, compensation and homeostasis in neuron and network function. Nat Rev Neurosci 7:563–574

    Article  CAS  PubMed  Google Scholar 

  • Miller KD (1994) Models of activity-dependent neural development.”. Prog Brain Res 102:303–318

    Article  CAS  PubMed  Google Scholar 

  • Milner LD, Landmesser LT (1999) Cholinergic and GABAergic inputs drive patterned spontaneous motoneuron activity before target contact. J Neurosci 19:3007–3022

    CAS  PubMed  Google Scholar 

  • O’Brien RJ, Kamboj S, Ehlers MD, Rosen KR, Fischbach GD, Huganir RL (1998) Activity-dependent modulation of synaptic AMPA receptor accumulation. Neuron 21:1067–1078

    Article  PubMed  Google Scholar 

  • O’Donovan MJ (1987) In vitro methods for the analysis of motor function in the developing spinal cord of the chick embryo. Med Sci Sports Exerc 19:S130–S133

    PubMed  Google Scholar 

  • O’Donovan MJ (1999) The origin of spontaneous activity in developing networks of the vertebrate nervous system. Curr Opin Neurobiol 9:94–104

    Article  PubMed  Google Scholar 

  • O’Donovan MJ, Chub N, Wenner P (1998) Mechanisms of spontaneous activity in developing spinal networks. J Neurobiol 37:131–145

    Article  PubMed  Google Scholar 

  • Owens DF, Kriegstein AR (2002) Is there more to GABA than synaptic inhibition? Nat Rev Neurosci 3:715–727

    Article  CAS  PubMed  Google Scholar 

  • Payne JA, Rivera C, Voipio J, Kaila K (2003) Cation-chloride co-transporters in neuronal communication, development and trauma. Trends Neurosci 26:199–206

    Article  CAS  PubMed  Google Scholar 

  • Persson M (1983) The role of movements in the development of sutural and diarthrodial joints tested by long-term paralysis of chick embryos. J Anat 137:591–599

    PubMed  Google Scholar 

  • Rich MM, Wenner P (2007) Sensing and expressing homeostatic synaptic plasticity. Trends Neurosci 30:119–125

    Article  CAS  PubMed  Google Scholar 

  • Ritter P, Wenner P, Ho S, Whelan PJ, O’Donovan MJ (1999) Activity patterns and synaptic organization of ventrally located interneurons in the embryonic chick spinal cord. J Neurosci 19:3457–3471

    CAS  PubMed  Google Scholar 

  • Roufa D, Martonosi AN (1981) Effect of curare on the development of chicken embryo skeletal muscle in ovo. Biochem Pharmacol 30:1501–1505

    Article  CAS  PubMed  Google Scholar 

  • Shatz CJ (1990) Impulse activity and the patterning of connections during CNS development. Neuron 5:745–756

    Article  CAS  PubMed  Google Scholar 

  • Singer JH, Berger AJ (2000) Development of inhibitory synaptic transmission to motoneurons. Brain Res Bull 53:553–560

    Article  CAS  PubMed  Google Scholar 

  • Stent GS (1973) A physiological mechanism for Hebb’s postulate of learning. Proc Natl Acad Sci U S A 70:997–1001

    Article  CAS  PubMed  Google Scholar 

  • Tabak J, Senn W, O’Donovan MJ, Rinzel J (2000) Modeling of spontaneous activity in developing spinal cord using activity-dependent depression in an excitatory network. J Neurosci 20:3041–3056

    CAS  PubMed  Google Scholar 

  • Tabak J, Rinzel J, and O’Donovan MJ (2001) The role of activity-dependent network depression in the expression and self-regulation of spontaneous activity in the developing spinal cord. J Neurosci 21:8966–8978.

    CAS  PubMed  Google Scholar 

  • Turrigiano GG, Abbott LF, Marder E (1994) Activity-dependent changes in the intrinsic properties of cultured neurons. Science 264:974–977

    Article  CAS  PubMed  Google Scholar 

  • Turrigiano GG, Leslie KR, Desai NS, Rutherford LC, Nelson SB (1998) Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature 391:892–896

    Article  CAS  PubMed  Google Scholar 

  • Turrigiano GG, Nelson SB (2004) Homeostatic plasticity in the developing nervous system. Nat Rev Neurosci 5:97–107

    Article  CAS  PubMed  Google Scholar 

  • Turrigiano G (2007) Homeostatic signaling: the positive side of negative feedback. Curr Opin Neurobiol 17:318–324

    Article  CAS  PubMed  Google Scholar 

  • Wenner P, O’Donovan MJ (2001) Mechanisms that initiate spontaneous network activity in the developing chick spinal cord. J Neurophysiol 86:1481–1498

    CAS  PubMed  Google Scholar 

  • Wilhelm J, Wenner P (2007) GABAA receptors: a potential sensor for homeostatic changes in GABAergic and AMPAergic synaptic strength in embryonic spinal cord. Soc for Neurosc Abstr 417:17

    Google Scholar 

  • Yao H, Dan Y (2005) Synaptic learning rules, cortical circuits, and visual function. Neuroscientist 11:206–216

    Article  PubMed  Google Scholar 

  • Yuste R, Nelson DA et al (1995) Neuronal domains in developing neocortex: mechanisms of coactivation. Neuron 14:7–17

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter Wenner .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Gonzalez-Islas, C.E., Wenner, P. (2010). Role of Spontaneous Activity in the Maturation of GABAergic Synapses in Embryonic Spinal Circuits. In: Pallas, S. (eds) Developmental Plasticity of Inhibitory Circuitry. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-1243-5_3

Download citation

Publish with us

Policies and ethics