Abstract
Mammalian cortical networks are active before synaptogenesis begins in earnest, before neuronal migration is complete, and well before an animal opens its eyes and begins to actively explore its surroundings. This early activity undergoes several transformations during development. The most important of these is a transition from episodic synchronous network events, which are necessary for patterning the neocortex into functionally related modules, to desynchronized activity that is computationally more powerful and efficient. Network desynchronization is perhaps the most dramatic and abrupt developmental event in an otherwise slow and gradual process of brain maturation. In this Review, we summarize what is known about the phenomenology of developmental synchronous activity in the rodent neocortex and speculate on the mechanisms that drive its eventual desynchronization. We argue that desynchronization of network activity is a fundamental step through which the cortex transitions from passive, bottom–up detection of sensory stimuli to active sensory processing with top–down modulation.
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References
Yuste, R., Peinado, A. & Katz, L. C. Neuronal domains in developing neocortex. Science 257, 665–669 (1992). Using calcium imaging, this paper describes synchronous network events in acute slices of the developing neocortex at P0–P7 (neuronal domains), which were insensitive to TTX and, therefore, independent of synaptic activity.
Leinekugel, X., Medina, I., Khalilov, I., Ben-Ari, Y. & Khazipov, R. Ca2+ oscillations mediated by the synergistic excitatory actions of GABA(A) and NMDA receptors in the neonatal hippocampus. Neuron 18, 243–255 (1997).
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. Nat. Neurosci. 3, 452–459 (2000).
Corlew, R., Bosma, M. M. & Moody, W. J. Spontaneous, synchronous electrical activity in neonatal mouse cortical neurons. J. Physiol. 560, 377–390 (2004).
Adelsberger, H., Garaschuk, O. & Konnerth, A. Cortical calcium waves in resting newborn mice. Nat. Neurosci. 8, 988–990 (2005). This research provides in vivo recordings of spontaneous calcium waves (synchronous network events) using two-photon imaging through an optical fibre.
Rochefort, N. L. et al. Sparsification of neuronal activity in the visual cortex at eye-opening. Proc. Natl Acad. Sci. USA 106, 15049–15054 (2009). This research provides evidence for sparsification of neuronal activity during the second postnatal week in V1 using in vivo two-photon calcium imaging.
Feller, M. B. Spontaneous correlated activity in developing neural circuits. Neuron 22, 653–656 (1999).
Ben-Ari, Y. Developing networks play a similar melody. Trends Neurosci. 24, 353–360 (2001).
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).
Allene, C. & Cossart, R. Early NMDA receptor-driven waves of activity in the developing neocortex: physiological or pathological network oscillations? J. Physiol. 588, 83–91 (2010).
Leighton, A. H. & Lohmann, C. The wiring of developing sensory circuits — from patterned spontaneous activity to synaptic plasticity mechanisms. Front. Neural Circuits 10, 71 (2016).
Colonnese, M. T. & Phillips, M. A. Thalamocortical function in developing sensory circuits. Curr. Opin. Neurobiol. 52, 72–79 (2018).
Luhmann, H. J. & Khazipov, R. Neuronal activity patterns in the developing barrel cortex. Neuroscience 368, 256–267 (2018).
Khazipov, R. & Milh, M. Early patterns of activity in the developing cortex: focus on the sensorimotor system. Semin. Cell Dev. Biol. 76, 120–129 (2018).
Molnar, Z., Luhmann, H. J. & Kanold, P. O. Transient cortical circuits match spontaneous and sensory-driven activity during development. Science 370, eabb2153 (2020).
Iannone, A. F. & De Marco Garcia, N. V. The emergence of network activity patterns in the somatosensory cortex — an early window to autism spectrum disorders. Neuroscience 466, 298–309 (2021).
Martini, F. J., Guillamon-Vivancos, T., Moreno-Juan, V., Valdeolmillos, M. & Lopez-Bendito, G. Spontaneous activity in developing thalamic and cortical sensory networks. Neuron 109, 2519–2534 (2021).
Dupont, E., Hanganu, I. L., Kilb, W., Hirsch, S. & Luhmann, H. J. Rapid developmental switch in the mechanisms driving early cortical columnar networks. Nature 439, 79–83 (2006).
Golshani, P. et al. Internally mediated developmental desynchronization of neocortical network activity. J. Neurosci. 29, 10890–10899 (2009). This research provides in vivo evidence of abrupt desynchronization in S1 in the second postnatal week using two-photon calcium imaging, and it shows evidence for the persistence of SNA after whisker deprivation, suggesting the intrinsic ability of cortical neurons to generate SNA independent of sensory inputs.
Siegel, F., Heimel, J. A., Peters, J. & Lohmann, C. Peripheral and central inputs shape network dynamics in the developing visual cortex in vivo. Curr. Biol. 22, 253–258 (2012).
Duan, Z. R. S. et al. GABAergic restriction of network dynamics regulates interneuron survival in the developing cortex. Neuron 105, 75–92.e5 (2020). This paper shows that co-occurrence of in vivo calcium SNA is observed in immature interneurons and pyramidal neurons.
Nakazawa, S., Yoshimura, Y., Takagi, M., Mizuno, H. & Iwasato, T. Developmental phase transitions in spatial organization of spontaneous activity in postnatal barrel cortex layer 4. J. Neurosci. 40, 7637–7650 (2020). This paper shows developmental transitions in the spontaneous activity of layer 4 neurons of the barrel cortex (first, from patchwork SNA to wave-like SNA, and then to desynchronized activity), as well as the dependence of only patchwork SNA on thalamic activity.
Kummer, M. et al. Column-like Ca(2+) clusters in the mouse neonatal neocortex revealed by three-dimensional two-photon Ca(2+) imaging in vivo. Neuroimage 138, 64–75 (2016).
Mizuno, H. et al. Patchwork-type spontaneous activity in neonatal barrel cortex layer 4 transmitted via thalamocortical projections. Cell Rep. 22, 123–135 (2018).
Che, A. et al. Layer I interneurons sharpen sensory maps during neonatal development. Neuron 99, 98–116.e7 (2018).
Maldonado, P. P. et al. Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons. Curr. Biol. 31, 322–333.e5 (2021).
Khazipov, R. et al. Early motor activity drives spindle bursts in the developing somatosensory cortex. Nature 432, 758–761 (2004). This research provides in vivo evidence of spindle bursts mediated by myoclonic twitches using electrophysiological recordings with silicon probes.
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).
Hanganu, I. L., Staiger, J. F., Ben-Ari, Y. & Khazipov, R. Cholinergic modulation of spindle bursts in the neonatal rat visual cortex in vivo. J. Neurosci. 27, 5694–5705 (2007).
Colonnese, M. T. et al. A conserved switch in sensory processing prepares developing neocortex for vision. Neuron 67, 480–498 (2010). This study shows that in vivo spindle bursts are conserved in preterm human neonates, and desynchronization occurs in both rats and humans (around birth in humans).
Maeda, E., Robinson, H. P. & Kawana, A. The mechanisms of generation and propagation of synchronized bursting in developing networks of cortical neurons. J. Neurosci. 15, 6834–6845 (1995).
Mohajerani, M. H. & Cherubini, E. Spontaneous recurrent network activity in organotypic rat hippocampal slices. Eur. J. Neurosci. 22, 107–118 (2005).
Johnson, H. A. & Buonomano, D. V. Development and plasticity of spontaneous activity and Up states in cortical organotypic slices. J. Neurosci. 27, 5915–5925 (2007).
Yang, J. W., Hanganu-Opatz, I. L., Sun, J. J. & Luhmann, H. J. Three patterns of oscillatory activity differentially synchronize developing neocortical networks in vivo. J. Neurosci. 29, 9011–9025 (2009).
Minlebaev, M., Colonnese, M., Tsintsadze, T., Sirota, A. & Khazipov, R. Early gamma oscillations synchronize developing thalamus and cortex. Science 334, 226–229 (2011).
Daw, M. I., Ashby, M. C. & Isaac, J. T. Coordinated developmental recruitment of latent fast spiking interneurons in layer IV barrel cortex. Nat. Neurosci. 10, 453–461 (2007).
Yang, J. W. et al. Thalamic network oscillations synchronize ontogenetic columns in the newborn rat barrel cortex. Cereb. Cortex 23, 1299–1316 (2013).
Bitzenhofer, S. H., Popplau, J. A. & Hanganu-Opatz, I. Gamma activity accelerates during prefrontal development. eLife 9, e56795 (2020).
Kirmse, K. et al. GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo. Nat. Commun. 6, 7750 (2015).
Babij, R. et al. Gabrb3 is required for the functional integration of pyramidal neuron subtypes in the somatosensory cortex. Neuron 111, 256–274.e10 (2022).
Chini, M., Pfeffer, T. & Hanganu-Opatz, I. An increase of inhibition drives the developmental decorrelation of neural activity. eLife 11, e78811 (2022). This research provides a computational model that makes predictions about the role of GABAergic inhibition in driving desynchronization, and its optogenetic experiments provide evidence supporting those predictions.
Kourdougli, N. et al. Improvement of sensory deficits in fragile X mice by increasing cortical interneuron activity after the critical period. Neuron 111, 2863–2880 (2023). This paper shows that interneurons and pyramidal neurons co-participate in SNA during development, and it provides all-optical in vivo evidence that activation of putative PV interneurons mediates network desynchronization during development.
Leighton, A. H. et al. Somatostatin interneurons restrict cell recruitment to retinally driven spontaneous activity in the developing cortex. Cell Rep. 36, 109316 (2021).
Bollmann, Y. et al. Prominent in vivo influence of single interneurons in the developing barrel cortex. Nat. Neurosci. 26, 1555–1565 (2023).
Modol, L. et al. Assemblies of perisomatic GABAergic neurons in the developing barrel cortex. Neuron 105, 93–105.e4 (2020). The authors of this research coined the term GABAergic calcium events (GCEs) to describe the co-occurrence of synchronous events in interneurons and excitatory neurons.
Gour, A. et al. Postnatal connectomic development of inhibition in mouse barrel cortex. Science 371, eabb4534 (2021).
Picardo, M. A. et al. Pioneer GABA cells comprise a subpopulation of hub neurons in the developing hippocampus. Neuron 71, 695–709 (2011). The paper provides a description of early-born GABAergic hub cells, which are SST-expressing interneurons that are highly connected to pyramidal neurons and are thought to have a crucial role in developmental synchrony.
Yuryev, M. et al. In vivo two-photon imaging of the embryonic cortex reveals spontaneous ketamine-sensitive calcium activity. Sci. Rep. 8, 16059 (2018).
Huang, Q. et al. Intravital imaging of mouse embryos. Science 368, 181–186 (2020).
Munz, M. et al. Pyramidal neurons form active, transient, multilayered circuits perturbed by autism-associated mutations at the inception of neocortex. Cell 186, 1930–1949 (2023). This paper uses para-uterine in vivo two-photon calcium imaging to record cortical neurons at early embryonic stages (E13.5–E18.5) in mice.
Anton-Bolaños, N. et al. Prenatal activity from thalamic neurons governs the emergence of functional cortical maps in mice. Science 364, 987–990 (2019). This research demonstrates patches of activity in S1 corresponding to thalamocortical events.
Mountcastle, V. B. Modality and topographic properties of single neurons of cat’s somatic sensory cortex. J. Neurophysiol. 20, 408–434 (1957).
Rakic, P. Specification of cerebral cortical areas. Science 241, 170–176 (1988).
Ackman, J. B., Burbridge, T. J. & Crair, M. C. Retinal waves coordinate patterned activity throughout the developing visual system. Nature 490, 219–225 (2012).
Ikezoe, K., Tamura, H., Kimura, F. & Fujita, I. Decorrelation of sensory-evoked neuronal responses in rat barrel cortex during postnatal development. Neurosci. Res. 73, 312–320 (2012).
Stern, E. A., Maravall, M. & Svoboda, K. Rapid development and plasticity of layer 2/3 maps in rat barrel cortex in vivo. Neuron 31, 305–315 (2001).
Dorrn, A. L., Yuan, K., Barker, A. J., Schreiner, C. E. & Froemke, R. C. Developmental sensory experience balances cortical excitation and inhibition. Nature 465, 932–936 (2010).
Shadlen, M. N. & Newsome, W. T. Noise, neural codes and cortical organization. Curr. Opin. Neurobiol. 4, 569–579 (1994).
Zohary, E., Shadlen, M. N. & Newsome, W. T. Correlated neuronal discharge rate and its implications for psychophysical performance. Nature 370, 140–143 (1994).
Olshausen, B. A. & Field, D. J. Sparse coding of sensory inputs. Curr. Opin. Neurobiol. 14, 481–487 (2004).
Colonnese, M. T. Rapid developmental emergence of stable depolarization during wakefulness by inhibitory balancing of cortical network excitability. J. Neurosci. 34, 5477–5485 (2014).
Babola, T. A. et al. Homeostatic control of spontaneous activity in the developing auditory system. Neuron 99, 511–524.e5 (2018).
Maffei, L. & Galli-Resta, L. Correlation in the discharges of neighboring rat retinal ganglion cells during prenatal life. Proc. Natl Acad. Sci. USA 87, 2861–2864 (1990).
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).
Weliky, M. & Katz, L. C. Correlational structure of spontaneous neuronal activity in the developing lateral geniculate nucleus in vivo. Science 285, 599–604 (1999).
Murata, Y. & Colonnese, M. T. An excitatory cortical feedback loop gates retinal wave transmission in rodent thalamus. eLife 5, e18816 (2016).
McVea, D. A., Mohajerani, M. H. & Murphy, T. H. Voltage-sensitive dye imaging reveals dynamic spatiotemporal properties of cortical activity after spontaneous muscle twitches in the newborn rat. J. Neurosci. 32, 10982–10994 (2012).
Moreno-Juan, V. et al. Prenatal thalamic waves regulate cortical area size prior to sensory processing. Nat. Commun. 8, 14172 (2017).
Akhmetshina, D., Nasretdinov, A., Zakharov, A., Valeeva, G. & Khazipov, R. The nature of the sensory input to the neonatal rat barrel cortex. J. Neurosci. 36, 9922–9932 (2016).
Riyahi, P., Phillips, M. A. & Colonnese, M. T. Input-independent homeostasis of developing thalamocortical activity. eNeuro 8, ENEURO.0184-21.2021 (2021).
Chiu, C. & Weliky, M. Spontaneous activity in developing ferret visual cortex in vivo. J. Neurosci. 21, 8906–8914 (2001).
Tiriac, A., Uitermarkt, B. D., Fanning, A. S., Sokoloff, G. & Blumberg, M. S. Rapid whisker movements in sleeping newborn rats. Curr. Biol. 22, 2075–2080 (2012).
Kandler, K. & Katz, L. C. Coordination of neuronal activity in developing visual cortex by gap junction-mediated biochemical communication. J. Neurosci. 18, 1419–1427 (1998).
Bennett, M. V. et al. Gap junctions: new tools, new answers, new questions. Neuron 6, 305–320 (1991).
Kumar, N. M. & Gilula, N. B. The gap junction communication channel. Cell 84, 381–388 (1996).
Sohl, G., Maxeiner, S. & Willecke, K. Expression and functions of neuronal gap junctions. Nat. Rev. Neurosci. 6, 191–200 (2005).
Montoro, R. J. & Yuste, R. Gap junctions in developing neocortex: a review. Brain Res. Rev. 47, 216–226 (2004).
Peinado, A., Yuste, R. & Katz, L. C. Gap junctional communication and the development of local circuits in neocortex. Cereb. Cortex 3, 488–498 (1993).
Yu, Y. C. et al. Preferential electrical coupling regulates neocortical lineage-dependent microcircuit assembly. Nature 486, 113–117 (2012).
Li, Y. et al. Clonally related visual cortical neurons show similar stimulus feature selectivity. Nature 486, 118–121 (2012).
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).
Allene, C. et al. Sequential generation of two distinct synapse-driven network patterns in developing neocortex. J. Neurosci. 28, 12851–12863 (2008).
Minlebaev, M., Ben-Ari, Y. & Khazipov, R. Network mechanisms of spindle-burst oscillations in the neonatal rat barrel cortex in vivo. J. Neurophysiol. 97, 692–700 (2007).
Minlebaev, M., Ben-Ari, Y. & Khazipov, R. NMDA receptors pattern early activity in the developing barrel cortex in vivo. Cereb. Cortex 19, 688–696 (2009).
Graf, J. et al. A limited role of NKCC1 in telencephalic glutamatergic neurons for developing hippocampal network dynamics and behavior. Proc. Natl Acad. Sci. USA 118, e2014784118 (2021).
Ben-Ari, Y., Cherubini, E., Corradetti, R. & Gaiarsa, J. L. Giant synaptic potentials in immature rat CA3 hippocampal neurons. J. Physiol. 416, 303–325 (1989). This research provides in vitro evidence for the depolarizing action of GABA in newborn rats.
Ben-Ari, Y. The GABA excitatory/inhibitory developmental sequence: a personal journey. Neuroscience 279, 187–219 (2014).
Murata, Y. & Colonnese, M. T. GABAergic interneurons excite neonatal hippocampus in vivo. Sci. Adv. 6, eaba1430 (2020). Using in vivo electrophysiological recordings coupled with optogenetics, this study provides in vivo confirmation of the excitatory actions of GABA in developing mice.
He, Q., Nomura, T., Xu, J. & Contractor, A. The developmental switch in GABA polarity is delayed in fragile X mice. J. Neurosci. 34, 446–450 (2014).
Deidda, G. et al. Early depolarizing GABA controls critical-period plasticity in the rat visual cortex. Nat. Neurosci. 18, 87–96 (2015).
Marguet, S. L. et al. Treatment during a vulnerable developmental period rescues a genetic epilepsy. Nat. Med. 21, 1436–1444 (2015).
Tuncdemir, S. N. et al. Early somatostatin interneuron connectivity mediates the maturation of deep layer cortical circuits. Neuron 89, 521–535 (2016).
Marques-Smith, A. et al. A transient translaminar GABAergic interneuron circuit connects thalamocortical recipient layers in neonatal somatosensory cortex. Neuron 89, 536–549 (2016).
Lee, S. H. & Dan, Y. Neuromodulation of brain states. Neuron 76, 209–222 (2012).
Riffault, B. et al. A quantitative cholinergic and catecholaminergic 3D Atlas of the developing mouse brain. Neuroimage 260, 119494 (2022).
Peinado, A. Traveling slow waves of neural activity: a novel form of network activity in developing neocortex. J. Neurosci. 20, RC54 (2000).
Cossart, R. & Garel, S. Step by step: cells with multiple functions in cortical circuit assembly. Nat. Rev. Neurosci. 23, 395–410 (2022).
Katz, L. C. & Shatz, C. J. Synaptic activity and the construction of cortical circuits. Science 274, 1133–1138 (1996).
Willshaw, D. J. & von der Malsburg, C. How patterned neural connections can be set up by self-organization. Proc. R. Soc. Lond. B Biol. Sci. 194, 431–445 (1976).
LeVay, S., Stryker, M. P. & Shatz, C. J. Ocular dominance columns and their development in layer IV of the cat’s visual cortex: a quantitative study. J. Comp. Neurol. 179, 223–244 (1978).
Senft, S. L. & Woolsey, T. A. Growth of thalamic afferents into mouse barrel cortex. Cereb. Cortex 1, 308–335 (1991).
Rebsam, A., Seif, I. & Gaspar, P. Refinement of thalamocortical arbors and emergence of barrel domains in the primary somatosensory cortex: a study of normal and monoamine oxidase a knock-out mice. J. Neurosci. 22, 8541–8552 (2002).
Higashi, S., Molnar, Z., Kurotani, T. & Toyama, K. Prenatal development of neural excitation in rat thalamocortical projections studied by optical recording. Neuroscience 115, 1231–1246 (2002).
Miller, B., Chou, L. & Finlay, B. L. The early development of thalamocortical and corticothalamic projections. J. Comp. Neurol. 335, 16–41 (1993).
Fox, K., Schlaggar, B. L., Glazewski, S. & O’Leary, D. D. Glutamate receptor blockade at cortical synapses disrupts development of thalamocortical and columnar organization in somatosensory cortex. Proc. Natl Acad. Sci. USA 93, 5584–5589 (1996).
Feller, M. B., Wellis, D. P., Stellwagen, D., Werblin, F. S. & Shatz, C. J. Requirement for cholinergic synaptic transmission in the propagation of spontaneous retinal waves. Science 272, 1182–1187 (1996).
Seabrook, T. A., Burbridge, T. J., Crair, M. C. & Huberman, A. D. Architecture, function, and assembly of the mouse visual system. Annu. Rev. Neurosci. 40, 499–538 (2017).
Stryker, M. P. & Harris, W. A. Binocular impulse blockade prevents the formation of ocular dominance columns in cat visual cortex. J. Neurosci. 6, 2117–2133 (1986).
Shatz, C. J. & Stryker, M. P. Prenatal tetrodotoxin infusion blocks segregation of retinogeniculate afferents. Science 242, 87–89 (1988).
Cang, J. et al. Development of precise maps in visual cortex requires patterned spontaneous activity in the retina. Neuron 48, 797–809 (2005).
Murakami, T., Matsui, T., Uemura, M. & Ohki, K. Modular strategy for development of the hierarchical visual network in mice. Nature 608, 578–585 (2022).
Gribizis, A. et al. Visual cortex gains independence from peripheral drive before eye opening. Neuron 104, 711–723.e3 (2019).
Clancy, K. B., Schnepel, P., Rao, A. T. & Feldman, D. E. Structure of a single whisker representation in layer 2 of mouse somatosensory cortex. J. Neurosci. 35, 3946–3958 (2015).
Favuzzi, E. et al. Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits. Science 363, 413–417 (2019).
Guan, W. et al. Eye opening differentially modulates inhibitory synaptic transmission in the developing visual cortex. eLife 6, e32337 (2017).
Sato, T. R. & Svoboda, K. The functional properties of barrel cortex neurons projecting to the primary motor cortex. J. Neurosci. 30, 4256–4260 (2010).
Wosniack, M. E. et al. Adaptation of spontaneous activity in the developing visual cortex. eLife 10, e61619 (2021).
Warm, D., Bassetti, D., Schroer, J., Luhmann, H. J. & Sinning, A. Spontaneous activity predicts survival of developing cortical neurons. Front. Cell Dev. Biol. 10, 937761 (2022).
Wong, F. K. et al. Pyramidal cell regulation of interneuron survival sculpts cortical networks. Nature 557, 668–673 (2018).
Priya, R. et al. Activity regulates cell death within cortical interneurons through a calcineurin-dependent mechanism. Cell Rep. 22, 1695–1709 (2018).
Denaxa, M. et al. Modulation of apoptosis controls inhibitory interneuron number in the cortex. Cell Rep. 22, 1710–1721 (2018).
Southwell, D. G. et al. Intrinsically determined cell death of developing cortical interneurons. Nature 491, 109–113 (2012).
Contractor, A., Ethell, I. M. & Portera-Cailliau, C. Cortical interneurons in autism. Nat. Neurosci. 24, 1648–1659 (2021).
He, C. X., Arroyo, E. D., Cantu, D. A., Goel, A. & Portera-Cailliau, C. A versatile method for viral transfection of calcium indicators in the neonatal mouse brain. Front. Neural Circuits 12, 56 (2018).
Smith, G. B. et al. The development of cortical circuits for motion discrimination. Nat. Neurosci. 18, 252–261 (2015).
van der Bourg, A. et al. Layer-specific refinement of sensory coding in developing mouse barrel cortex. Cereb. Cortex 27, 4835–4850 (2017).
Arakawa, H. & Erzurumlu, R. S. Role of whiskers in sensorimotor development of C57BL/6 mice. Behav. Brain Res. 287, 146–155 (2015).
Grant, R. A., Mitchinson, B. & Prescott, T. J. The development of whisker control in rats in relation to locomotion. Dev. Psychobiol. 54, 151–168 (2012).
Micheva, K. D. & Beaulieu, C. Quantitative aspects of synaptogenesis in the rat barrel field cortex with special reference to GABA circuitry. J. Comp. Neurol. 373, 340–354 (1996).
Brochini, L. et al. Phase transitions and self-organized criticality in networks of stochastic spiking neurons. Sci. Rep. 6, 35831 (2016).
Picken Bahrey, H. L. & Moody, W. J. Early development of voltage-gated ion currents and firing properties in neurons of the mouse cerebral cortex. J. Neurophysiol. 89, 1761–1773 (2003).
Lim, L., Mi, D., Llorca, A. & Marin, O. Development and functional diversification of cortical interneurons. Neuron 100, 294–313 (2018).
Konig, N., Roch, G. & Marty, R. The onset of synaptogenesis in rat temporal cortex. Anat. Embryol. 148, 73–87 (1975).
Owens, D. F., Liu, X. & Kriegstein, A. R. Changing properties of GABA(A) receptor-mediated signaling during early neocortical development. J. Neurophysiol. 82, 570–583 (1999).
Modol, L., Moissidis, M., Selten, M., Oozeer, F. & Marin, O. Somatostatin interneurons control the timing of developmental desynchronization in cortical networks. Neuron https://doi.org/10.1016/j.neuron.2024.03.014 (2024).
del Rio, J. A., de Lecea, L., Ferrer, I. & Soriano, E. The development of parvalbumin-immunoreactivity in the neocortex of the mouse. Brain Res. Dev. Brain Res. 81, 247–259 (1994).
Du, J., Zhang, L., Weiser, M., Rudy, B. & McBain, C. J. Developmental expression and functional characterization of the potassium-channel subunit Kv3.1b in parvalbumin-containing interneurons of the rat hippocampus. J. Neurosci. 16, 506–518 (1996).
Rudy, B. & McBain, C. J. Kv3 channels: voltage-gated K+ channels designed for high-frequency repetitive firing. Trends Neurosci. 24, 517–526 (2001).
Kaczmarek, L. K. & Zhang, Y. Kv3 channels: enablers of rapid firing, neurotransmitter release, and neuronal endurance. Physiol. Rev. 97, 1431–1468 (2017).
Elbert, A. et al. CTCF governs the identity and migration of MGE-derived cortical interneurons. J. Neurosci. 39, 177–192 (2019).
Gonchar, Y., Wang, Q. & Burkhalter, A. Multiple distinct subtypes of GABAergic neurons in mouse visual cortex identified by triple immunostaining. Front. Neuroanat. 1, 3 (2007).
Muhlethaler, M., Charpak, S. & Dreifuss, J. J. Contrasting effects of neurohypophysial peptides on pyramidal and non-pyramidal neurons in the rat hippocampus. Brain Res. 308, 97–107 (1984).
Owen, S. F. et al. Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons. Nature 500, 458–462 (2013).
Spoljaric, A. et al. Vasopressin excites interneurons to suppress hippocampal network activity across a broad span of brain maturity at birth. Proc. Natl Acad. Sci. USA 114, E10819–E10828 (2017).
Ben-Ari, Y. Excitatory actions of GABA during development: the nature of the nurture. Nat. Rev. Neurosci. 3, 728–739 (2002).
Tyzio, R. et al. Postnatal changes in somatic gamma-aminobutyric acid signalling in the rat hippocampus. Eur. J. Neurosci. 27, 2515–2528 (2008).
van Rheede, J. J., Richards, B. A. & Akerman, C. J. Sensory-evoked spiking behavior emerges via an experience-dependent plasticity mechanism. Neuron 87, 1050–1062 (2015).
Valeeva, G., Tressard, T., Mukhtarov, M., Baude, A. & Khazipov, R. An optogenetic approach for investigation of excitatory and inhibitory network GABA actions in mice expressing channelrhodopsin-2 in GABAergic neurons. J. Neurosci. 36, 5961–5973 (2016).
Kurki, S. N. et al. Expression patterns of NKCC1 in neurons and non-neuronal cells during cortico-hippocampal development. Cereb. Cortex 33, 5906–5923 (2023).
Rivera, C. et al. The K+/Cl− co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 397, 251–255 (1999). This study provides evidence that the GABA polarity shift depends on the developmental expression of the K–Cl co-transporter KCC2 in the developing hippocampus.
Ludwig, A., Li, H., Saarma, M., Kaila, K. & Rivera, C. Developmental up-regulation of KCC2 in the absence of GABAergic and glutamatergic transmission. Eur. J. Neurosci. 18, 3199–3206 (2003).
Hevner, R. F., Neogi, T., Englund, C., Daza, R. A. & Fink, A. Cajal-Retzius cells in the mouse: transcription factors, neurotransmitters, and birthdays suggest a pallial origin. Brain Res. Dev. Brain Res. 141, 39–53 (2003).
Bielle, F. et al. Multiple origins of Cajal-Retzius cells at the borders of the developing pallium. Nat. Neurosci. 8, 1002–1012 (2005).
Chowdhury, T. G. et al. Fate of Cajal-Retzius neurons in the postnatal mouse neocortex. Front. Neuroanat. 4, 10 (2010).
Radnikow, G., Feldmeyer, D. & Lubke, J. Axonal projection, input and output synapses, and synaptic physiology of Cajal-Retzius cells in the developing rat neocortex. J. Neurosci. 22, 6908–6919 (2002).
Aguilo, A. et al. Involvement of Cajal-Retzius neurons in spontaneous correlated activity of embryonic and postnatal layer 1 from wild-type and reeler mice. J. Neurosci. 19, 10856–10868 (1999).
Kostovic, I. & Rakic, P. Developmental history of the transient subplate zone in the visual and somatosensory cortex of the macaque monkey and human brain. J. Comp. Neurol. 297, 441–470 (1990).
Allendoerfer, K. L. & Shatz, C. J. The subplate, a transient neocortical structure: its role in the development of connections between thalamus and cortex. Annu. Rev. Neurosci. 17, 185–218 (1994).
Marx, M. et al. Neocortical layer 6B as a remnant of the subplate — a morphological comparison. Cereb. Cortex 27, 1011–1026 (2017).
Kanold, P. O. & Luhmann, H. J. The subplate and early cortical circuits. Annu. Rev. Neurosci. 33, 23–48 (2010).
Wess, J. M., Isaiah, A., Watkins, P. V. & Kanold, P. O. Subplate neurons are the first cortical neurons to respond to sensory stimuli. Proc. Natl Acad. Sci. USA 114, 12602–12607 (2017).
Kerschensteiner, D. Spontaneous network activity and synaptic development. Neuroscientist 20, 272–290 (2014).
Tolner, E. A., Sheikh, A., Yukin, A. Y., Kaila, K. & Kanold, P. O. Subplate neurons promote spindle bursts and thalamocortical patterning in the neonatal rat somatosensory cortex. J. Neurosci. 32, 692–702 (2012).
Ghezzi, F. et al. Non-canonical role for Lpar1-EGFP subplate neurons in early postnatal mouse somatosensory cortex. eLife 10, e60810 (2021).
Trujillo, C. A. et al. Complex oscillatory waves emerging from cortical organoids model early human brain network development. Cell Stem Cell 25, 558–569.e7 (2019).
Sharf, T. et al. Functional neuronal circuitry and oscillatory dynamics in human brain organoids. Nat. Commun. 13, 4403 (2022).
Bonifazi, P. et al. GABAergic hub neurons orchestrate synchrony in developing hippocampal networks. Science 326, 1419–1424 (2009).
Marissal, T. et al. Pioneer glutamatergic cells develop into a morpho-functionally distinct population in the juvenile CA3 hippocampus. Nat. Commun. 3, 1316 (2012).
Cheng, S. et al. Vision-dependent specification of cell types and function in the developing cortex. Cell 185, 311–327.e24 (2022).
Huang, E. J. & Reichardt, L. F. Neurotrophins: roles in neuronal development and function. Annu. Rev. Neurosci. 24, 677–736 (2001).
Hensch, T. K. Critical period plasticity in local cortical circuits. Nat. Rev. Neurosci. 6, 877–888 (2005).
Romagnoni, A., Colonnese, M. T., Touboul, J. D. & Gutkin, B. S. Progressive alignment of inhibitory and excitatory delay may drive a rapid developmental switch in cortical network dynamics. J. Neurophysiol. 123, 1583–1599 (2020).
Milh, M. et al. Rapid cortical oscillations and early motor activity in premature human neonate. Cereb. Cortex 17, 1582–1594 (2007).
Destexhe, A., Hughes, S. W., Rudolph, M. & Crunelli, V. Are corticothalamic ‘up’ states fragments of wakefulness? Trends Neurosci. 30, 334–342 (2007).
Crepel, V. et al. A parturition-associated nonsynaptic coherent activity pattern in the developing hippocampus. Neuron 54, 105–120 (2007).
Grienberger, C., Giovannucci, A., Zeiger, W. & Portera-Cailliau, C. Two-photon calcium imaging of neuronal activity. Nat. Rev. Methods Primers 2, 6 (2022).
Mire, E. et al. Spontaneous activity regulates Robo1 transcription to mediate a switch in thalamocortical axon growth. Nat. Neurosci. 15, 1134–1143 (2012).
Dard, R. F. et al. The rapid developmental rise of somatic inhibition disengages hippocampal dynamics from self-motion. eLife 11, e78116 (2022).
Leprince, E. et al. Extrinsic control of the early postnatal CA1 hippocampal circuits. Neuron 111, 888–902.e8 (2023).
Valeeva, G. et al. Emergence of coordinated activity in the developing entorhinal-hippocampal network. Cereb. Cortex 29, 906–920 (2019).
Leinekugel, X. et al. Correlated bursts of activity in the neonatal hippocampus in vivo. Science 296, 2049–2052 (2002).
Inacio, A. R., Nasretdinov, A., Lebedeva, J. & Khazipov, R. Sensory feedback synchronizes motor and sensory neuronal networks in the neonatal rat spinal cord. Nat. Commun. 7, 13060 (2016).
Dehorter, N. et al. Onset of pup locomotion coincides with loss of NR2C/D-mediated cortico-striatal EPSCs and dampening of striatal network immature activity. Front. Cell Neurosci. 5, 24 (2011).
Ferrari, D. C. et al. Midbrain dopaminergic neurons generate calcium and sodium currents and release dopamine in the striatum of pups. Front. Cell Neurosci. 6, 7 (2012).
Akin, O., Bajar, B. T., Keles, M. F., Frye, M. A. & Zipursky, S. L. Cell-type-specific patterned stimulus-independent neuronal activity in the Drosophila visual system during synapse formation. Neuron 101, 894–904.e5 (2019).
Bajar, B. T. et al. A discrete neuronal population coordinates brain-wide developmental activity. Nature 602, 639–646 (2022).
Xu, H., Khakhalin, A. S., Nurmikko, A. V. & Aizenman, C. D. Visual experience-dependent maturation of correlated neuronal activity patterns in a developing visual system. J. Neurosci. 31, 8025–8036 (2011).
Suarez, R. et al. Cortical activity emerges in region-specific patterns during early brain development. Proc. Natl Acad. Sci. USA 120, e2208654120 (2023).
Steriade, M., Nunez, A. & Amzica, F. A novel slow (<1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components. J. Neurosci. 13, 3252–3265 (1993).
Jercog, D. et al. UP-DOWN cortical dynamics reflect state transitions in a bistable network. eLife 6, e22425 (2017).
Soldado-Magraner, S., Seay, M. J., Laje, R. & Buonomano, D. V. Paradoxical self-sustained dynamics emerge from orchestrated excitatory and inhibitory homeostatic plasticity rules. Proc. Natl Acad. Sci. USA 119, e2200621119 (2022).
Hoffman, K. L. et al. The upshot of up states in the neocortex: from slow oscillations to memory formation. J. Neurosci. 27, 11838–11841 (2007).
Sanchez-Vives, M. V. & McCormick, D. A. Cellular and network mechanisms of rhythmic recurrent activity in neocortex. Nat. Neurosci. 3, 1027–1034 (2000).
Constantinople, C. M. & Bruno, R. M. Effects and mechanisms of wakefulness on local cortical networks. Neuron 69, 1061–1068 (2011).
Goncalves, J. T., Anstey, J. E., Golshani, P. & Portera-Cailliau, C. Circuit level defects in the developing neocortex of fragile X mice. Nat. Neurosci. 16, 903–909 (2013). This study provides in vivo evidence of cortical network hypersynchrony and delayed desynchronization in a mouse model of fragile X syndrome.
Namiki, S. et al. Layer III neurons control synchronized waves in the immature cerebral cortex. J. Neurosci. 33, 987–1001 (2013).
Shen, J. & Colonnese, M. T. Development of activity in the mouse visual cortex. J. Neurosci. 36, 12259–12275 (2016).
Dreyfus-Brisac, C. & Larroche, J. C. Électroencéphalogrammes discontinus du nouveau-né prématuré et à terme. Corrélations électro-anatomo-cliniques. Rev. Electroencéphalogr. Neurophysiol. Clin. 1, 95–99 (1971).
Iyer, K. K. et al. Cortical burst dynamics predict clinical outcome early in extremely preterm infants. Brain 138, 2206–2218 (2015).
Bitzenhofer, S. H., Popplau, J. A., Chini, M., Marquardt, A. & Hanganu-Opatz, I. L. A transient developmental increase in prefrontal activity alters network maturation and causes cognitive dysfunction in adult mice. Neuron 109, 1350–1364.e6 (2021).
Cheyne, J. E., Zabouri, N., Baddeley, D. & Lohmann, C. Spontaneous activity patterns are altered in the developing visual cortex of the Fmr1 knockout mouse. Front. Neural Circuits 13, 57 (2019).
Kourdougli, N. & Portera-Cailliau, C. aGABRacadabra: a surprising new role for GABA(A) receptors in cortical development. Neuron 111, 146–149 (2023).
La Fata, G. et al. FMRP regulates multipolar to bipolar transition affecting neuronal migration and cortical circuitry. Nat. Neurosci. 17, 1693–1700 (2014).
Samarasinghe, R. A. et al. Identification of neural oscillations and epileptiform changes in human brain organoids. Nat. Neurosci. 24, 1488–1500 (2021).
Penagarikano, O. et al. Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell 147, 235–246 (2011).
Acknowledgements
We are grateful to M. Colonnese, M. Dipoppa and C. Lohmann for feedback on earlier versions of this manuscript. When citing papers, we attempted to be as inclusive as possible in acknowledging the many investigators whose work has helped shape our ideas; however, we recognize that we have probably missed attributing credit in some cases, and we apologize for any inadvertent oversights. This work was supported by the following grants: Department of Defense (DOD, 13196175), R01NS117597 (NIH-NINDS), R01HD108370 and R01HD054453 (NIH-NICHD) awarded to C.P.-C., by a fellowship grant from the FRAXA research foundation to N.K., and by the Training Grant in Neurobehavioral Genetics (T32NS048004; NIH, NINDS) and the UCLA-Caltech Medical Scientist Training Program (T32 GM008042; NIH, NIGMS) to M.W.W.
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Glossary
- Early network oscillations
-
(ENOs). Synchronous network events recorded in vitro using calcium imaging in the hippocampus and neocortex during the first postnatal week and driven by glutamatergic neurotransmission.
- GABAergic calcium events
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(GCEs). Synchronous calcium events specifically involving GABAergic interneurons.
- Gap junctions
-
Structures consisting of heteromeric connexin channels in the plasma membrane that form direct conduits between adjacent cells and allow the rapid exchange of small molecules between neighbouring neurons; they are responsible for the dye coupling phenomenon observed in whole cell patch clamp recordings in acute brain slices.
- Giant depolarizing potentials
-
(GDPs). Spontaneous network-mediated synaptic events observed in vitro in the developing hippocampus that are driven by GABAergic neurotransmission.
- Neural oscillations
-
Emergent phenomena of brain circuits that reflect the rhythmic or repetitive firing patterns of groups of neurons. Oscillations can occur spontaneously or in response to sensory stimuli, and they often reflect the interaction between excitation and inhibition.
- Neuronal domains
-
Gap junction-mediated calcium signals that appear synchronously across small clusters of neighbouring neurons in acute brain slices from the neocortex; they are not mediated by action potentials, and it is unclear whether they occur in vivo.
- Patchwork SNA
-
The predominant pattern of SNA seen between E18 and P7 in the rodent neocortex. In patchwork SNA, largely non-overlapping well-circumscribed clusters or patches of neurons fire synchronously, with their firing being separated in time by long periods of quiescence.
- Sparsification
-
A process occurring alongside desynchronization, in which the network activity transitions to a state in which relatively few neurons within the population are firing at any given time.
- Spindle bursts
-
A specific pattern of spontaneous neural activity observed in the immature cortex using electrophysiology that is characterized by a fast oscillatory component (approximately 4–20 Hz) occurring on top of a slower delta wave. Spindle bursts are brief (<2 s) and reflect the synchronous firing of many neurons.
- Synchronous network activity
-
(SNA). Synchronous activity occurring during development that is mediated by chemical synapses and involves most of the neurons within a local network, manifesting either as brief (<3 s) bursts of activity within clusters of neighbouring cells or as larger events that propagate locally within a cortical region.
- Up states
-
Stable depolarized states of the resting membrane potential (Vm) during which action potentials may occur. They are brief (<2 s) and separated by periods when the Vm is more hyperpolarized (Down state) and action potentials do not tend to occur. Transitions between Up and Down states are seen during sleep or quiet wakefulness.
- Wave-like SNA
-
The main pattern of SNA observed in rodent neocortex during the second postnatal week. Wave-like SNA involves large, partially overlapping neuronal ensembles and the activity propagates haltingly, between short periods of quiescence.
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Wu, M.W., Kourdougli, N. & Portera-Cailliau, C. Network state transitions during cortical development. Nat. Rev. Neurosci. (2024). https://doi.org/10.1038/s41583-024-00824-y
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DOI: https://doi.org/10.1038/s41583-024-00824-y
