During development, several different circuits of the CNS spontaneously generate correlated firing patterns that are distinct from activity patterns observed in the mature state.
The spontaneously active circuits described here are the spinal cord, cochlea, retina, hippocampus and cerebellum.
Although spontaneously active circuits have unique architectures, they use similar strategies to generate activity.
One of the common features is the existence of transient excitatory networks, consisting of depolarizing GABA (γ-aminobutyric acid), transient synaptic connections or gap junction coupling.
Another common feature is the presence of pacemaker-like neurons that are involved in the spontaneous generation of events.
There are many examples in which the absence of a crucial network component leads to the generation of spontaneous correlated activity by a compensatory circuit. This indicates that a given region of the CNS can use multiple strategies to generate spontaneous activity.
Patterned, spontaneous activity occurs in many developing neural circuits, including the retina, the cochlea, the spinal cord, the cerebellum and the hippocampus, where it provides signals that are important for the development of neurons and their connections. Despite there being differences in adult architecture and output across these various circuits, the patterns of spontaneous network activity and the mechanisms that generate it are remarkably similar. The mechanisms can include a depolarizing action of GABA (γ-aminobutyric acid), transient synaptic connections, extrasynaptic transmission, gap junction coupling and the presence of pacemaker-like neurons. Interestingly, spontaneous activity is robust; if one element of a circuit is disrupted another will generate similar activity. This research suggests that developing neural circuits exhibit transient and tunable features that maintain a source of correlated activity during crucial stages of development.
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Owens, D. F. & Kriegstein, A. R. Is there more to GABA than synaptic inhibition? Nature Rev. Neurosci. 3, 715–727 (2002).
Spitzer, N. C. Electrical activity in early neuronal development. Nature 444, 707–712 (2006).
Galli, L. & Maffei, L. Spontaneous impulse activity of rat retinal ganglion cells in prenatal life. Science 242, 90–91 (1988).
Meister, M., Wong, R. O., Baylor, D. A. & Shatz, C. J. Synchronous bursts of action potentials in ganglion cells of the developing mammalian retina. Science 252, 939–943 (1991).
Tritsch, N. X., Yi, E., Gale, J. E., Glowatzki, E. & Bergles, D. E. The origin of spontaneous activity in the developing auditory system. Nature 450, 50–55 (2007). The first description of spontaneous correlated activity in the developing cochlea. This study uses a combination of physiology and imaging techniques to implicate release of ATP in the generation of correlated activity.
Torborg, C. L. & Feller, M. B. Spontaneous patterned retinal activity and the refinement of retinal projections. Prog. Neurobiol. 76, 213–235 (2005).
Forsythe, I. D. Hearing: a fantasia on Kolliker's organ. Nature 450, 43–44 (2007).
Kandler, K., Clause, A. & Noh, J. Tonotopic reorganization of developing auditory brainstem circuits. Nature Neurosci. 12, 711–717 (2009).
Landmesser, L. T. & O'Donovan, M. J. Activation patterns of embryonic chick hind limb muscles recorded in ovo and in an isolated spinal cord preparation. J. Physiol. 347, 189–204 (1984).
Hanson, M. G., Milner, L. D. & Landmesser, L. T. Spontaneous rhythmic activity in early chick spinal cord influences distinct motor axon pathfinding decisions. Brain Res. Rev. 57, 77–85 (2008).
Gonzalez-Islas, C. & Wenner, P. Spontaneous network activity in the embryonic spinal cord regulates AMPAergic and GABAergic synaptic strength. Neuron 49, 563–575 (2006). Although this is not the first demonstration of homeostatic regulation of spinal cord activity, the authors showed that spontaneous network activity influences the relative strength of excitatory and inhibitory synapses. It also demonstrated homeostatic regulation of synaptic strength in an intact circuit.
Myers, C. P. et al. Cholinergic input is required during embryonic development to mediate proper assembly of spinal locomotor circuits. Neuron 46, 37–49 (2005).
Marder, E. & Rehm, K. J. Development of central pattern generating circuits. Curr. Opin. Neurobiol. 15, 86–93 (2005).
Ben-Ari, Y., Cherubini, E., Corradetti, R. & Gaiarsa, J. L. Giant synaptic potentials in immature rat CA3 hippocampal neurones. J. Physiol. 416, 303–325 (1989).
Garaschuk, O., Hanse, E. & Konnerth, A. Developmental profile and synaptic origin of early network oscillations in the CA1 region of rat neonatal hippocampus. J. Physiol. 507, 219–236 (1998).
Garaschuk, O., Linn, J., Eilers, J. & Konnerth, A. Large-scale oscillatory calcium waves in the immature cortex. Nature Neurosci. 3, 452–459 (2000).
Corlew, R., Bosma, M. M. & Moody, W. J. Spontaneous, synchronous electrical activity in neonatal mouse cortical neurones. J. Physiol. 560, 377–390 (2004).
Gust, J., Wright, J. J., Pratt, E. B. & Bosma, M. M. Development of synchronized activity of cranial motor neurons in the segmented embryonic mouse hindbrain. J. Physiol. 550, 123–133 (2003).
Rockhill, W., Kirkman, J. L. & Bosma, M. M. Spontaneous activity in the developing mouse midbrain driven by an external pacemaker. Dev. Neurobiol. 69, 689–704 (2009).
Watt, A. J. et al. Traveling waves in developing cerebellar cortex mediated by asymmetrical Purkinje cell connectivity. Nature Neurosci. 12, 463–473 (2009). This study used various physiological and modelling techniques to describe the phenomenon of and mechanisms underlying spontaneous network activity in the developing cerebellum.
Moody, W. J. & Bosma, M. M. Ion channel development, spontaneous activity, and activity-dependent development in nerve and muscle cells. Physiol. Rev. 85, 883–941 (2005). This comprehensive review includes detailed descriptions of the physiological changes underlying spontaneous activity in developing circuits.
Mohajerani, M. H. & Cherubini, E. Role of giant depolarizing potentials in shaping synaptic currents in the developing hippocampus. Crit. Rev. Neurobiol. 18, 13–23 (2006).
Khazipov, R. & Luhmann, H. J. Early patterns of electrical activity in the developing cerebral cortex of humans and rodents. Trends Neurosci. 29, 414–418 (2006). This review provides an overview of the mechanisms underlying spontaneous network activation in the developing neocortex, a circuit not covered in our Review.
Wong, R. O., Meister, M. & Shatz, C. J. Transient period of correlated bursting activity during development of the mammalian retina. Neuron 11, 923–938 (1993).
Mooney, R., Penn, A. A., Gallego, R. & Shatz, C. J. Thalamic relay of spontaneous retinal activity prior to vision. Neuron 17, 863–874 (1996).
Weliky, M. & Katz, L. C. Correlational structure of spontaneous neuronal activity in the developing lateral geniculate nucleus in vivo. Science 285, 599–604 (1999).
Hanganu, I. L., Ben-Ari, Y. & Khazipov, R. Retinal waves trigger spindle bursts in the neonatal rat visual cortex. J. Neurosci. 26, 6728–6736 (2006).
Hamburger, V. Some aspects of the embryology of behavior. Q. Rev. Biol. 38, 342–365 (1963).
Provine, R. R. Ontogeny of bioelectric activity in the spinal cord of the chick embryo and its behavioral implications. Brain Res. 41, 365–378 (1972).
Milner, L. D. & Landmesser, L. T. Cholinergic and GABAergic inputs drive patterned spontaneous motoneuron activity before target contact. J. Neurosci. 19, 3007–3022 (1999).
Yvert, B., Branchereau, P. & Meyrand, P. Multiple spontaneous rhythmic activity patterns generated by the embryonic mouse spinal cord occur within a specific developmental time window. J. Neurophysiol. 91, 2101–2109 (2004).
Ren, J. & Greer, J. J. Ontogeny of rhythmic motor patterns generated in the embryonic rat spinal cord. J. Neurophysiol. 89, 1187–1195 (2003).
Xu, H., Whelan, P. J. & Wenner, P. Development of an inhibitory interneuronal circuit in the embryonic spinal cord. J. Neurophysiol. 93, 2922–2933 (2005).
Bekoff, A. Ontogeny of leg motor output in the chick embryo: a neural analysis. Brain Res. 106, 271–291 (1976).
Crepel, V. et al. A parturition-associated nonsynaptic coherent activity pattern in the developing hippocampus. Neuron 54, 105–120 (2007).
Allene, C. et al. Sequential generation of two distinct synapse-driven network patterns in developing neocortex. J. Neurosci. 28, 12851–12863 (2008).
Leinekugel, X., Medina, I., Khalilov, I., Ben-Ari, Y. & Khazipov, R. Ca2+ oscillations mediated by the synergistic excitatory actions of GABAA and NMDA receptors in the neonatal hippocampus. Neuron 18, 243–255 (1997).
Gummer, A. W. & Mark, R. F. Patterned neural activity in brain stem auditory areas of a prehearing mammal, the tammar wallaby (Macropus eugenii). Neuroreport 5, 685–688 (1994).
Jones, T. A., Jones, S. M. & Paggett, K. C. Primordial rhythmic bursting in embryonic cochlear ganglion cells. J. Neurosci. 21, 8129–8135 (2001).
Jones, T. A., Leake, P. A., Snyder, R. L., Stakhovskaya, O. & Bonham, B. Spontaneous discharge patterns in cochlear spiral ganglion cells before the onset of hearing in cats. J. Neurophysiol. 98, 1898–1908 (2007).
Lippe, W. R. Rhythmic spontaneous activity in the developing avian auditory system. J. Neurosci. 14, 1486–1495 (1994).
Harris-Warrick, R. M. Voltage-sensitive ion channels in rhythmic motor systems. Curr. Opin. Neurobiol. 12, 646–651 (2002).
Biel, M., Wahl-Schott, C., Michalakis, S. & Zong, X. Hyperpolarization-activated cation channels: from genes to function. Physiol. Rev. 89, 847–885 (2009).
Rybak, I. A., Abdala, A. P., Markin, S. N., Paton, J. F. & Smith, J. C. Spatial organization and state-dependent mechanisms for respiratory rhythm and pattern generation. Prog. Brain Res. 165, 201–220 (2007).
Bond, C. T., Maylie, J. & Adelman, J. P. SK channels in excitability, pacemaking and synaptic integration. Curr. Opin. Neurobiol. 15, 305–311 (2005).
Raman, I. M. & Bean, B. P. Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons. J. Neurosci. 17, 4517–4526 (1997).
Ben-Ari, Y., Gaiarsa, J. L., Tyzio, R. & Khazipov, R. GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol. Rev. 87, 1215–1284 (2007). This review describes the many functions of depolarizing GABA throughout the development of the nervious system, including the generation of giant depolarizing potentials.
Sipila, S. T. & Kaila, K. GABAergic control of CA3-driven network events in the developing hippocampus. Res. Probl. Cell Differ. 44, 99–121 (2008).
Sipila, S. T., Huttu, K., Voipio, J. & Kaila, K. Intrinsic bursting of immature CA3 pyramidal neurons and consequent giant depolarizing potentials are driven by a persistent Na+ current and terminated by a slow Ca2+ -activated K+ current. Eur. J. Neurosci. 23, 2330–2338 (2006).
Sipila, S. T., Huttu, K., Soltesz, I., Voipio, J. & Kaila, K. Depolarizing GABA acts on intrinsically bursting pyramidal neurons to drive giant depolarizing potentials in the immature hippocampus. J. Neurosci. 25, 5280–5289 (2005). This study highlights how the spontaneous bursting in CA3 pyramidal cells coupled with network interactions is responsible for initiating events in the developing hippocampus.
Lischalk, J. W., Easton, C. R. & Moody, W. J. Bilaterally propagating waves of spontaneous activity arising from discrete pacemakers in the neonatal mouse cerebral cortex. Dev. Neurobiol. 69, 407–414 (2009).
Butts, D. A., Feller, M. B., Shatz, C. J. & Rokhsar, D. S. Retinal waves are governed by collective network properties. J. Neurosci. 19, 3580–3593 (1999).
Godfrey, K. B. & Swindale, N. V. Retinal wave behavior through activity-dependent refractory periods. PLoS Comput. Biol. 3, e245 (2007).
Zheng, J., Lee, S. & Zhou, Z. J. A transient network of intrinsically bursting starburst cells underlies the generation of retinal waves. Nature Neurosci. 9, 363–371 (2006). This important study described pacemaker-like properties in an excitatory interneuron involved in retinal wave generation.
Zhou, Z. J. The function of the cholinergic system in the developing mammalian retina. Prog. Brain Res. 131, 599–613 (2001).
Zheng, J. J., Lee, S. & Zhou, Z. J. A developmental switch in the excitability and function of the starburst network in the mammalian retina. Neuron 44, 851–864 (2004).
Lancaster, B. & Nicoll, R. A. Properties of two calcium-activated hyperpolarizations in rat hippocampal neurones. J. Physiol. 389, 187–203 (1987).
Sah, P. & Isaacson, J. S. Channels underlying the slow afterhyperpolarization in hippocampal pyramidal neurons: neurotransmitters modulate the open probability. Neuron 15, 435–441 (1995).
Sah, P. Ca2+-activated K+ currents in neurones: types, physiological roles and modulation. Trends Neurosci. 19, 150–154 (1996).
Sah, P. & Faber, E. S. Channels underlying neuronal calcium-activated potassium currents. Prog. Neurobiol. 66, 345–353 (2002).
Vogalis, F., Storm, J. F. & Lancaster, B. SK channels and the varieties of slow after-hyperpolarizations in neurons. Eur. J. Neurosci. 18, 3155–3166 (2003).
Goaillard, J. M. & Vincent, P. Serotonin suppresses the slow afterhyperpolarization in rat intralaminar and midline thalamic neurones by activating 5-HT(7) receptors. J. Physiol. 541, 453–465 (2002).
Neylon, C. B., Fowler, C. J. & Furness, J. B. Regulation of the slow afterhyperpolarization in enteric neurons by protein kinase A. Auton. Neurosci. 126–127, 258–263 (2006).
Stellwagen, D., Shatz, C. J. & Feller, M. B. Dynamics of retinal waves are controlled by cyclic AMP. Neuron 24, 673–685 (1999).
Hennig, M. H., Adams, C., Willshaw, D. & Sernagor, E. Early-stage waves in the retinal network emerge close to a critical state transition between local and global functional connectivity. J. Neurosci. 29, 1077–1086 (2009).
Hanson, M. G. & Landmesser, L. T. Characterization of the circuits that generate spontaneous episodes of activity in the early embryonic mouse spinal cord. J. Neurosci. 23, 587–600 (2003). This paper was crucial for determining the changing circuits that mediate spontaneous network activity in the mouse spinal cord.
Wenner, P. & O'Donovan, M. J. Mechanisms that initiate spontaneous network activity in the developing chick spinal cord. J. Neurophysiol. 86, 1481–1498 (2001).
Arai, Y., Mentis, G. Z., Wu, J. Y. & O'Donovan, M. J. Ventrolateral origin of each cycle of rhythmic activity generated by the spinal cord of the chick embryo. PLoS ONE 2, e417 (2007).
Chub, N. & O'Donovan, M. J. Post-episode depression of GABAergic transmission in spinal neurons of the chick embryo. J. Neurophysiol. 85, 2166–2176 (2001).
Fedirchuk, B. et al. Spontaneous network activity transiently depresses synaptic transmission in the embryonic chick spinal cord. J. Neurosci. 19, 2102–2112 (1999).
Marchetti, C., Tabak, J., Chub, N., O'Donovan, M. J. & Rinzel, J. Modeling spontaneous activity in the developing spinal cord using activity-dependent variations of intracellular chloride. J. Neurosci. 25, 3601–3612 (2005). This study combined physiological recordings and computational modelling to describe how GABAergic signalling could dictate the frequency of network events in developing chick spinal cord.
Tabak, J., Senn, W., O'Donovan, M. J. & Rinzel, J. Modeling of spontaneous activity in developing spinal cord using activity-dependent depression in an excitatory network. J. Neurosci. 20, 3041–3056 (2000).
Chub, N., Mentis, G. Z. & O'Donovan, M. J. Chloride-sensitive MEQ fluorescence in chick embryo motoneurons following manipulations of chloride and during spontaneous network activity. J. Neurophysiol. 95, 323–330 (2006).
Ben-Ari, Y. Excitatory actions of GABA during development: the nature of the nurture. Nature Rev. Neurosci. 3, 728–739 (2002).
Blaesse, P., Airaksinen, M. S., Rivera, C. & Kaila, K. Cation-chloride cotransporters and neuronal function. Neuron 61, 820–838 (2009).
Zhang, L. L., Pathak, H. R., Coulter, D. A., Freed, M. A. & Vardi, N. Shift of intracellular chloride concentration in ganglion and amacrine cells of developing mouse retina. J. Neurophysiol. 95, 2404–2416 (2006).
Leitch, E., Coaker, J., Young, C., Mehta, V. & Sernagor, E. GABA type-A activity controls its own developmental polarity switch in the maturing retina. J. Neurosci. 25, 4801–4805 (2005).
Sernagor, E., Young, C. & Eglen, S. J. Developmental modulation of retinal wave dynamics: shedding light on the GABA saga. J. Neurosci. 23, 7621–7629 (2003).
Wang, C. T. et al. GABA(A) receptor-mediated signaling alters the structure of spontaneous activity in the developing retina. J. Neurosci. 27, 9130–9140 (2007).
O'Donovan, M. J., Chub, N. & Wenner, P. Mechanisms of spontaneous activity in developing spinal networks. J. Neurobiol. 37, 131–145 (1998).
Nishimaru, H., Restrepo, C. E., Ryge, J., Yanagawa, Y. & Kiehn, O. Mammalian motor neurons corelease glutamate and acetylcholine at central synapses. Proc. Natl Acad. Sci. USA 102, 5245–5249 (2005).
Mentis, G. Z. et al. Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord. Proc. Natl Acad. Sci. USA 102, 7344–7349 (2005).
Mentis, G. Z., Siembab, V. C., Zerda, R., O'Donovan, M. J. & Alvarez, F. J. Primary afferent synapses on developing and adult Renshaw cells. J. Neurosci. 26, 13297–13310 (2006).
Demarque, M. et al. Paracrine intercellular communication by a Ca2+- and SNARE-independent release of GABA and glutamate prior to synapse formation. Neuron 36, 1051–1061 (2002).
LoTurco, J. J., Owens, D. F., Heath, M. J., Davis, M. B. & Kriegstein, A. R. GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis. Neuron 15, 1287–1298 (1995).
Manent, J. B. et al. A noncanonical release of GABA and glutamate modulates neuronal migration. J. Neurosci. 25, 4755–4765 (2005).
Blankenship, A. G. et al. Synaptic and extrasynaptic factors governing glutamatergic retinal waves. Neuron 62, 230–241 (2009). This recent study implicated glutamate spillover in retinal waves and showed that the absence of glutamatergic waves prevented the cessation of cholinergic retinal waves.
Chen, S. & Diamond, J. S. Synaptically released glutamate activates extrasynaptic NMDA receptors on cells in the ganglion cell layer of rat retina. J. Neurosci. 22, 2165–2173 (2002).
DeVries, S. H., Li, W. & Saszik, S. Parallel processing in two transmitter microenvironments at the cone photoreceptor synapse. Neuron 50, 735–748 (2006).
Veruki, M. L., Morkve, S. H. & Hartveit, E. Activation of a presynaptic glutamate transporter regulates synaptic transmission through electrical signaling. Nature Neurosci. 9, 1388–1396 (2006).
Sernagor, E., Eglen, S. J. & O'Donovan, M. J. Differential effects of acetylcholine and glutamate blockade on the spatiotemporal dynamics of retinal waves. J. Neurosci. 20, RC56 (2000).
Demarque, M. et al. Glutamate transporters prevent the generation of seizures in the developing rat neocortex. J. Neurosci. 24, 3289–3294 (2004).
Milh, M., Becq, H., Villeneuve, N., Ben-Ari, Y. & Aniksztejn, L. Inhibition of glutamate transporters results in a “suppression-burst” pattern and partial seizures in the newborn rat. Epilepsia 48, 169–174 (2007).
Cattani, A. A., Bonfardin, V. D., Represa, A., Ben-Ari, Y. & Aniksztejn, L. Generation of slow network oscillations in the developing rat hippocampus after blockade of glutamate uptake. J. Neurophysiol. 98, 2324–2336 (2007).
Sharifullina, E. & Nistri, A. Glutamate uptake block triggers deadly rhythmic bursting of neonatal rat hypoglossal motoneurons. J. Physiol. 572, 407–423 (2006).
Bansal, A. et al. Mice lacking specific nicotinic acetylcholine receptor subunits exhibit dramatically altered spontaneous activity patterns and reveal a limited role for retinal waves in forming ON and OFF circuits in the inner retina. J. Neurosci. 20, 7672–7681 (2000).
Syed, M. M., Lee, S., Zheng, J. & Zhou, Z. J. Stage-dependent dynamics and modulation of spontaneous waves in the developing rabbit retina. J. Physiol. 560, 533–549 (2004).
Singer, J. H., Mirotznik, R. R. & Feller, M. B. Potentiation of L-type calcium channels reveals nonsynaptic mechanisms that correlate spontaneous activity in the developing mammalian retina. J. Neurosci. 21, 8514–8522 (2001).
Vessey, J. P. et al. Carbenoxolone inhibition of voltage-gated Ca channels and synaptic transmission in the retina. J. Neurophysiol. 92, 1252–1256 (2004).
Takeda, Y., Ward, S. M., Sanders, K. M. & Koh, S. D. Effects of the gap junction blocker glycyrrhetinic acid on gastrointestinal smooth muscle cells. Am. J. Physiol. Gastrointest. Liver Physiol. 288, G832–G841 (2005).
Sheu, S. J., Bee, Y. S. & Chen, C. H. Resveratrol and large-conductance calcium-activated potassium channels in the protection of human retinal pigment epithelial cells. J. Ocul. Pharmacol. Ther. 24, 551–555 (2008).
Wu, S. N., Jan, C. R. & Chiang, H. T. Fenamates stimulate BKCa channel osteoblast-like MG-63 cells activity in the human. J. Investig. Med. 49, 522–533 (2001).
Tovar, K. R., Maher, B. J. & Westbrook, G. L. Direct actions of carbenoxolone on synaptic transmission and neuronal membrane properties. J. Neurophysiol. 102, 974–978 (2009).
Chang, Q., Gonzalez, M., Pinter, M. J. & Balice-Gordon, R. J. Gap junctional coupling and patterns of connexin expression among neonatal rat lumbar spinal motor neurons. J. Neurosci. 19, 10813–10828 (1999).
Personius, K. E., Chang, Q., Mentis, G. Z., O'Donovan, M. J. & Balice-Gordon, R. J. Reduced gap junctional coupling leads to uncorrelated motor neuron firing and precocious neuromuscular synapse elimination. Proc. Natl Acad. Sci. USA 104, 11808–11813 (2007).
Torborg, C. L., Hansen, K. A. & Feller, M. B. High frequency, synchronized bursting drives eye-specific segregation of retinogeniculate projections. Nature Neurosci. 8, 72–78 (2005).
Hansen, K. A., Torborg, C. L., Elstrott, J. & Feller, M. B. Expression and function of the neuronal gap junction protein connexin 36 in developing mammalian retina. J. Comp. Neurol. 493, 309–320 (2005).
Turrigiano, G. Maintaining your youthful spontaneity: microcircuit homeostasis in the embryonic spinal cord. Neuron 49, 481–483 (2006).
Chub, N. & O'Donovan, M. J. Blockade and recovery of spontaneous rhythmic activity after application of neurotransmitter antagonists to spinal networks of the chick embryo. J. Neurosci. 18, 294–306 (1998).
Wilhelm, J. C. & Wenner, P. GABAA transmission is a critical step in the process of triggering homeostatic increases in quantal amplitude. Proc. Natl Acad. Sci. USA 105, 11412–11417 (2008).
Wilhelm, J. C., Rich, M. M. & Wenner, P. Compensatory changes in cellular excitability, not synaptic scaling, contribute to homeostatic recovery of embryonic network activity. Proc. Natl Acad. Sci. USA 106, 6760–6765 (2009).
Stacy, R. C., Demas, J., Burgess, R. W., Sanes, J. R. & Wong, R. O. Disruption and recovery of patterned retinal activity in the absence of acetylcholine. J. Neurosci. 25, 9347–9357 (2005).
McLaughlin, T., Torborg, C. L., Feller, M. B. & O'Leary, D. D. Retinotopic map refinement requires spontaneous retinal waves during a brief critical period of development. Neuron 40, 1147–1160 (2003).
Sun, C., Warland, D. K., Ballesteros, J. M., van der List, D. & Chalupa, L. M. Retinal waves in mice lacking the β2 subunit of the nicotinic acetylcholine receptor. Proc. Natl Acad. Sci. USA 105, 13638–13643 (2008).
Stafford, B. K., Sher, A., Litke, A. M. & Feldheim, D. A. Spatial-temporal patterns of retinal waves underlying activity-dependent refinement of retinofugal projections. Neuron 64, 200–212 (2009).
Torborg, C., Wang, C. T., Muir-Robinson, G. & Feller, M. B. L-type calcium channel agonist induces correlated depolarizations in mice lacking the β2 subunit nAChRs. Vision Res. 44, 3347–3355 (2004).
Mochida, H., Sato, K. & Momose-Sato, Y. Switching of the transmitters that mediate hindbrain correlated activity in the chick embryo. Eur. J. Neurosci. 29, 14–30 (2009).
Sipila, S. T. et al. Compensatory enhancement of intrinsic spiking upon NKCC1 disruption in neonatal hippocampus. J. Neurosci. 29, 6982–6988 (2009).
Pfeffer, C. K. et al. NKCC1-dependent GABAergic excitation drives synaptic network maturation during early hippocampal development. J. Neurosci. 29, 3419–3430 (2009).
Galindo, R. & Valenzuela, C. F. Immature hippocampal neuronal networks do not develop tolerance to the excitatory actions of ethanol. Alcohol 40, 111–118 (2006).
Stromland, K. Visual impairment and ocular abnormalities in children with fetal alcohol syndrome. Addict. Biol. 9, 153–157; discussion 159–160 (2004).
Medina, A. E., Krahe, T. E. & Ramoa, A. S. Early alcohol exposure induces persistent alteration of cortical columnar organization and reduced orientation selectivity in the visual cortex. J. Neurophysiol. 93, 1317–1325 (2005).
Tyzio, R. et al. Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery. Science 314, 1788–1792 (2006).
Leinekugel, X. Developmental patterns and plasticities: the hippocampal model. J. Physiol. (Paris) 97, 27–37 (2003).
Leinekugel, X. et al. Correlated bursts of activity in the neonatal hippocampus in vivo. Science 296, 2049–2052 (2002).
Support provided by National Science Foundation grant IOS-0818983 (M.F.) and US National Institutes of Health grants RO1EY013528 (M.F.) and F31NS058167 (A.B.). The authors thank D. Bergles and P. Wenner for critical comments on the manuscript.
The authors declare no competing financial interests.
- Extrasynaptic transmission
Neurotransmitter-mediated signalling through a pathway other than a direct synaptic connection. One example is spillover, in which synaptically released neurotransmitter diffuses out of the synapse and activates extrasynaptic receptors or synaptic receptors located in neighbouring synapses. A second example is volume transmission, in which neurotransmitter is released directly into the non-synaptic extracellular space.
- Gap junctions
Intercellular channels composed of connexin proteins that are the basis of electrical synapses between neurons.
- Retinal ganglion cells
The projection neurons of the retina, the axons of which form the optic nerve.
- Central pattern generator
A neural circuit that produces self-sustaining patterns of behaviour independently of sensory input.
- Pacemaker-like neuron
In the adult nervous system, pacemaker neurons possess a set of ion channels that lead to regular patterns of depolarization and hyperpolarization. In developing circuits, pacemaker-like neurons are neurons with unstable membrane potentials, the pacemaker properties of which also depend on network interactions.
- Amacrine cell
A retinal interneuron located in the inner nuclear or ganglion cell layer of the retina that provides local inhibition in the adult retina.
- Renshaw cell
A GABAergic interneuron that receives excitatory input from motor neurons.
- Bipolar cell
An interneuron of the retina that provides excitatory glutamatergic input to retinal ganglion cells. In the adult retina, bipolar cells receive input from photoreceptors.
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Blankenship, A., Feller, M. Mechanisms underlying spontaneous patterned activity in developing neural circuits. Nat Rev Neurosci 11, 18–29 (2010). https://doi.org/10.1038/nrn2759
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