Spontaneous Network Activity in the Embryonic Spinal Cord Regulates AMPAergic and GABAergic Synaptic Strength

Spontaneous network activity (SNA) has been described in most developing circuits, including the spinal cord, retina, and hippocampus. Despite the widespread nature of this developmental phenomenon, its role in network maturation is poorly understood. We reduced SNA in the intact embryo and found compensatory increases in synaptic strength of spinal motoneuron inputs. AMPAergic miniature postsynaptic current (mPSC) amplitude and frequency increased following the reduction of activity. Interestingly, excitatory GABAergic mPSCs also increase in amplitude through a process of synaptic scaling. Finally, the normal modulation of GABAergic mPSC amplitude was accelerated. Together, these compensatory responses appear to increase the excitability of the cord and could act to maintain appropriate SNA levels, thus demonstrating a distinct functional role for synaptic homeostasis. Because spontaneous network activity can regulate AMPAergic and GABAergic synaptic strength during development, SNA is likely to play an important role in a coordinated maturation of excitatory and inhibitory synaptic strength.

[1]  R. Wong,et al.  Retinal waves and visual system development. , 1999, Annual review of neuroscience.

[2]  Y. Ben-Ari,et al.  Nature and nurture in brain development , 2004, Trends in Neurosciences.

[3]  M. Feller,et al.  Spontaneous Correlated Activity in Developing Neural Circuits , 1999, Neuron.

[4]  M. Hanson,et al.  Normal Patterns of Spontaneous Activity Are Required for Correct Motor Axon Guidance and the Expression of Specific Guidance Molecules , 2004, Neuron.

[5]  Michael J. O'Donovan The origin of spontaneous activity in developing networks of the vertebrate nervous system , 1999, Current Opinion in Neurobiology.

[6]  S W Herring,et al.  Paralysis and growth of the musculoskeletal system in the embryonic chick , 1990, Journal of morphology.

[7]  Michael J. O'Donovan,et al.  Activity Patterns and Synaptic Organization of Ventrally Located Interneurons in the Embryonic Chick Spinal Cord , 1999, The Journal of Neuroscience.

[8]  J. A. Payne,et al.  The K+/Cl− co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation , 1999, Nature.

[9]  R. Tsien,et al.  Adaptation to Synaptic Inactivity in Hippocampal Neurons , 2005, Neuron.

[10]  S. Ho,et al.  Spontaneous activity in the perinatal trigeminal nucleus of the rat. , 1999, Neuroreport.

[11]  Michael J. O'Donovan,et al.  Post-episode depression of GABAergic transmission in spinal neurons of the chick embryo. , 2001, Journal of neurophysiology.

[12]  J. Champagnat,et al.  Rhythm generation in the segmented hindbrain of chick embryos. , 1995, The Journal of physiology.

[13]  Michael J. O'Donovan,et al.  Blockade and Recovery of Spontaneous Rhythmic Activity after Application of Neurotransmitter Antagonists to Spinal Networks of the Chick Embryo , 1998, The Journal of Neuroscience.

[14]  R. Nicoll,et al.  Activity differentially regulates the surface expression of synaptic AMPA and NMDA glutamate receptors. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[15]  G. Turrigiano,et al.  Postsynaptic Expression of Homeostatic Plasticity at Neocortical Synapses , 2005, The Journal of Neuroscience.

[16]  Niraj S. Desai,et al.  Activity-dependent scaling of quantal amplitude in neocortical neurons , 1998, Nature.

[17]  Nicholas C. Spitzer,et al.  Activity-dependent homeostatic specification of transmitter expression in embryonic neurons , 2004, Nature.

[18]  V. Murthy,et al.  Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons , 2002, Nature.

[19]  R. Huganir,et al.  Activity-Dependent Modulation of Synaptic AMPA Receptor Accumulation , 1998, Neuron.

[20]  Martin Wilson,et al.  Variation in GABA mini amplitude is the consequence of variation in transmitter concentration , 1995, Neuron.

[21]  S. Molotchnikoff,et al.  Evolution of spontaneous activity in the developing rat superior colliculus. , 1995, Canadian journal of physiology and pharmacology.

[22]  L. Ballerini,et al.  Opposite changes in synaptic activity of organotypic rat spinal cord cultures after chronic block of AMPA/kainate or glycine and GABAA receptors , 2000, The Journal of physiology.

[23]  G. Davis,et al.  Maintaining the stability of neural function: a homeostatic hypothesis. , 2001, Annual review of physiology.

[24]  J. Paysan,et al.  Switch in the expression of rat GABAA-receptor subtypes during postnatal development: an immunohistochemical study , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[25]  M. D. Ross Granville Harrison,et al.  An experimental study of the relation of the nervous system to the developing musculature in the embryo of the frog , 1904 .

[26]  V. Hamburger The developmental history of the motor neuron. , 1977, Neurosciences Research Program bulletin.

[27]  H. Atwood,et al.  Diversification of synaptic strength: presynaptic elements , 2002, Nature Reviews Neuroscience.

[28]  J. Sanes,et al.  Gamma protocadherins are required for synaptic development in the spinal cord. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Y. Ben-Ari,et al.  Giant synaptic potentials in immature rat CA3 hippocampal neurones. , 1989, The Journal of physiology.

[30]  John Rinzel,et al.  Modeling Spontaneous Activity in the Developing Spinal Cord Using Activity-Dependent Variations of Intracellular Chloride , 2005, The Journal of Neuroscience.

[31]  W. Lippe Relationship between frequency of spontaneous bursting and tonotopic position in the developing avian auditory system , 1995, Brain Research.

[32]  Michael J. O'Donovan,et al.  Mechanisms of spontaneous activity in developing spinal networks. , 1998, Journal of neurobiology.

[33]  Michael D. Ehlers,et al.  Homeostatic plasticity and NMDA receptor trafficking , 2005, Trends in Neurosciences.

[34]  H. Atwood,et al.  Quantal Size and Variation Determined by Vesicle Size in Normal and Mutant Drosophila Glutamatergic Synapses , 2002, The Journal of Neuroscience.

[35]  R F Mark,et al.  Patterned neural activity in brain stem auditory areas of a prehearing mammal, the tammar wallaby (Macropus eugenii). , 1994, Neuroreport.

[36]  M. Toutant,et al.  Enzymatic differentiation of muscle fibre types in embryonic latissimus dorsii of the chick: effects of spinal cord stimulation. , 1979, Cell differentiation.

[37]  M. Schäfer,et al.  Homeostatic Scaling of Vesicular Glutamate and GABA Transporter Expression in Rat Neocortical Circuits , 2005, The Journal of Neuroscience.

[38]  C. Shatz,et al.  Synaptic Activity and the Construction of Cortical Circuits , 1996, Science.

[39]  E Marder,et al.  Memory from the dynamics of intrinsic membrane currents. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Y. Ben-Ari Developing networks play a similar melody , 2001, Trends in Neurosciences.

[41]  S. Salmons,et al.  Induction of a fast-oxidative phenotype by chronic muscle stimulation: mechanical and biochemical studies. , 1996, The American journal of physiology.

[42]  Michael J. O'Donovan,et al.  Mechanisms that initiate spontaneous network activity in the developing chick spinal cord. , 2001, Journal of neurophysiology.

[43]  B. Mendelson,et al.  Specific monosynaptic sensory-motor connections form in the absence of patterned neural activity and motoneuronal cell death , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[44]  V. Murthy,et al.  Synaptic gain control and homeostasis , 2003, Current Opinion in Neurobiology.

[45]  R. Tsien,et al.  alpha- and betaCaMKII. Inverse regulation by neuronal activity and opposing effects on synaptic strength. , 2002, Neuron.

[46]  Michael J. O'Donovan,et al.  The Role of Activity-Dependent Network Depression in the Expression and Self-Regulation of Spontaneous Activity in the Developing Spinal Cord , 2001, The Journal of Neuroscience.

[47]  W. Rall Time constants and electrotonic length of membrane cylinders and neurons. , 1969, Biophysical journal.

[48]  Viktor Hamburger,et al.  A series of normal stages in the development of the chick embryo , 1992, Journal of morphology.

[49]  Mark C. W. van Rossum,et al.  Activity Deprivation Reduces Miniature IPSC Amplitude by Decreasing the Number of Postsynaptic GABAA Receptors Clustered at Neocortical Synapses , 2002, The Journal of Neuroscience.

[50]  Li I. Zhang,et al.  Electrical activity and development of neural circuits , 2001, Nature Neuroscience.

[51]  J. Kapur,et al.  Activity-dependent scaling of GABAergic synapse strength is regulated by brain-derived neurotrophic factor , 2006, Molecular and Cellular Neuroscience.

[52]  D. Ruano-Gil,et al.  Influence of extrinsic factors on the development of the articular system. , 1978, Acta anatomica.

[53]  L. Haverkamp,et al.  Anatomical and physiological development of the Xenopus embryonic motor system in the absence of neural activity , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[54]  S. Nelson,et al.  Homeostatic plasticity in the developing nervous system , 2004, Nature Reviews Neuroscience.

[55]  Y. Ben-Ari Excitatory actions of gaba during development: the nature of the nurture , 2002, Nature Reviews Neuroscience.

[56]  S. Nelson,et al.  Selective reconfiguration of layer 4 visual cortical circuitry by visual deprivation , 2004, Nature Neuroscience.

[57]  J. Isaac Postsynaptic silent synapses: evidence and mechanisms , 2003, Neuropharmacology.

[58]  R. Oppenheim,et al.  Behavioral development in the absence of neural activity: effects of chronic immobilization on amphibian embryos , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[59]  Nicholas C Spitzer,et al.  Activity-dependent neuronal differentiation prior to synapse formation: the functions of calcium transients , 2002, Journal of Physiology-Paris.

[60]  R. Tsien,et al.  α- and βCaMKII Inverse Regulation by Neuronal Activity and Opposing Effects on Synaptic Strength , 2002, Neuron.

[61]  M. Persson The role of movements in the development of sutural and diarthrodial joints tested by long-term paralysis of chick embryos. , 1983, Journal of anatomy.

[62]  Michael J. O'Donovan,et al.  Modeling of Spontaneous Activity in Developing Spinal Cord Using Activity-Dependent Depression in an Excitatory Network , 2000, The Journal of Neuroscience.

[63]  Niraj S. Desai,et al.  Critical periods for experience-dependent synaptic scaling in visual cortex , 2002, Nature Neuroscience.

[64]  D. Laurie,et al.  The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. II. Olfactory bulb and cerebellum , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[65]  E. Marder,et al.  Selective regulation of current densities underlies spontaneous changes in the activity of cultured neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[66]  M. Hanson,et al.  Characterization of the Circuits That Generate Spontaneous Episodes of Activity in the Early Embryonic Mouse Spinal Cord , 2003, The Journal of Neuroscience.

[67]  L. Landmesser,et al.  Cholinergic and GABAergic Inputs Drive Patterned Spontaneous Motoneuron Activity before Target Contact , 1999, The Journal of Neuroscience.

[68]  E. Marder,et al.  Activity-dependent changes in the intrinsic properties of cultured neurons. , 1994, Science.

[69]  M. Pinter,et al.  Activity-Dependent Presynaptic Regulation of Quantal Size at the Mammalian Neuromuscular Junction In Vivo , 2005, The Journal of Neuroscience.

[70]  P. Stein,et al.  Coordinated motor output in the hindlimb of the 7-day chick embryo. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[71]  G. Davis,et al.  Homeostatic Control of Presynaptic Release Is Triggered by Postsynaptic Membrane Depolarization , 2001, Neuron.

[72]  V. Hamburger,et al.  A series of normal stages in the development of the chick embryo. 1951. , 2012, Developmental dynamics : an official publication of the American Association of Anatomists.

[73]  R. Nicoll,et al.  Expression mechanisms underlying long-term potentiation: a postsynaptic view. , 2003, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[74]  Nathan R. Wilson,et al.  Presynaptic Regulation of Quantal Size by the Vesicular Glutamate Transporter VGLUT1 , 2005, The Journal of Neuroscience.

[75]  A. Martonosi,et al.  Effect of curare on the development of chicken embryo skeletal muscle in ovo. , 1981, Biochemical pharmacology.

[76]  Michael J. O'Donovan,et al.  Spontaneous Network Activity Transiently Depresses Synaptic Transmission in the Embryonic Chick Spinal Cord , 1999, The Journal of Neuroscience.