The influence of early experience on the development of sensory systems

Current Opinion in Neurobiology

Volumn 14, Issue 4, 2004, Pages 503-512

  Grubb, Matthew S ^a   Thompson, Ian D ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BRAIN DEVELOPMENT; BRAIN FUNCTION; EXPERIENCE; HUMAN; MOLECULAR DYNAMICS; NERVE CELL NETWORK; NERVE CONDUCTION; NONHUMAN; PRIORITY JOURNAL; REVIEW; SENSORY STIMULATION; SENSORY SYSTEM; SYNAPSE;

ACTION POTENTIALS; AFFERENT PATHWAYS; ANIMALS; BRAIN; CELL DIFFERENTIATION; GROWTH CONES; HUMANS; NEURONAL PLASTICITY; NEURONS, AFFERENT; RETINA; SENSATION;

EID: 4043059988     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.conb.2004.06.006     Document Type: Review

References (67)

1. D.H. Hubel, and T.N. Wiesel Receptive fields of cells in striate cortex of very young, visually inexperienced kittens J Neurophysiol 26 1963 994 1000
2. D.H. Hubel, and T.N. Wiesel Binocular interaction in striate cortex of kittens reared with artificial squint J Neurophysiol 28 1965 1041 1059
3. N. Jain, P.S. Diener, J.O. Coq, and J.H. Kaas Patterned activity via spinal dorsal quadrant inputs is necessary for the formation of organized somatosensory maps J Neurosci 23 2003 10321 10330
4. D.F. McLaughlin, and S.L. Juliano Developmental regulation of plasticity in the forepaw representation of ferret somatosensory cortex J Neurophysiol 89 2003 2289 2298
5. J.F. Olavarria, and R. Hiroi Retinal influences specify cortico-cortical maps by postnatal day six in rats and mice J Comp Neurol 459 2003 156 172
6. C. Vale, J. Schoorlemmer, and D.H. Sanes Deafness disrupts chloride transporter function and inhibitory synaptic transmission J Neurosci 23 2003 7516 7524
7. H.C. Wu, E. Lecain, I. Chiappini, T.H. Yang, and P. Tran Ba Huy Influence of auditory deprivation upon the tonopic organization in the inferior colliculus: a Fos immunocytochemical study in the rat Eur J Neurosci 17 2003 2540 2552
8. M. Meister, R.O. Wong, D.A. Baylor, and C.J. Shatz Synchronous bursts of action potentials in ganglion cells of the developing mammalian retina Science 252 1991 939 943
9. D.A. McCormick, F. Trent, and A.S. Ramoa Postnatal development of synchronized network oscillations in the ferret dorsal lateral geniculate and perigeniculate nuclei J Neurosci 15 1995 5739 5752
10. R. Yuste, D.A. Nelson, W.W. Rubin, and L.C. Katz Neuronal domains in developing neocortex: mechanisms of coactivation Neuron 14 1995 7 17
11. T.A. Jones, S.M. Jones, and K.C. Paggett Primordial rhythmic bursting in embryonic cochlear ganglion cells J Neurosci 21 2001 8129 8135
12. S.J. Eglen The role of retinal waves and synaptic normalization in retinogeniculate development Philos Trans R Soc Lond B Biol Sci 354 1999 497 506
13. D.A. Butts, and D.S. Rokhsar The information content of spontaneous retinal waves J Neurosci 21 2001 961 973
14. A.A. Penn, P.A. Riquelme, M.B. Feller, and C.J. Shatz Competition in retinogeniculate patterning driven by spontaneous activity Science 279 1998 2108 2112
15. D. Stellwagen, and C.J. Shatz An instructive role for retinal waves in the development of retinogeniculate connectivity Neuron 33 2002 357 367
16. ••], this suggests that neonatal patterns of retinal spontaneous activity instruct the development of fine retinotopic maps in the visual system.
17. A.D. Huberman, G.Y. Wang, L.C. Liets, O.A. Collins, B. Chapman, and L.M. Chalupa Eye-specific retinogeniculate segregation independent of normal neuronal activity Science 300 2003 994 998. Paired in vitro recordings in the neonatal ferret retina show that correlations in firing between close neighbouring RGCs are abolished when a specific cholinergic cell population is reduced by immunotoxin treatment. The manipulation, however, does not affect overall RGC firing rates. This selective alteration in patterns rather than levels of spontaneous activity is not accompanied by any anatomical abnormalities in the ocular segregation of the lateral geniculate nucleus. Spontaneous activity could therefore be purely permissive for the development of this organisational feature of the ferret visual system.
18. F.M. Rossi, T. Pizzorusso, V. Porciatti, L.M. Marubio, L. Maffei, and J.P. Changeux Requirement of the nicotinic acetylcholine receptor beta 2 subunit for the anatomical and functional development of the visual system Proc Natl Acad Sci USA 98 2001 6453 6458
19. G. Muir-Robinson, B.J. Hwang, and M.B. Feller Retinogeniculate axons undergo eye-specific segregation in the absence of eye-specific layers J Neurosci 22 2002 5259 5264
20. ••], these data suggest that patterns of spontaneous activity in the neonatal retina are vital for the development of normal functional organisation in the visual system.
21. L.M. Chalupa, and C.J. Snider Topographic specificity in the retinocollicular projection of the developing ferret: an anterograde tracing study J Comp Neurol 392 1998 35 47
22. D.K. Simon, and D.D. O'Leary Development of topographic order in the mammalian retinocollicular projection J Neurosci 12 1992 1212 1232
23. J. Demas, S.J. Eglen, and R.O. Wong Developmental loss of synchronous spontaneous activity in the mouse retina is independent of visual experience J Neurosci 23 2003 2851 2860. The authors describe the quantitative features of spontaneous retinal activity at various stages of pre- and post-eye opening development in mice. Dark-rearing from birth shows that early experience has extremely little effect on the properties of intrinsic spiking in neonatal mammalian retinae.
24. K. Krug, C.J. Akerman, and I.D. Thompson Responses of neurons in neonatal cortex and thalamus to patterned visual stimulation through the naturally closed lids J Neurophysiol 85 2001 1436 1443
25. C.J. Akerman, D. Smyth, and I.D. Thompson Visual experience before eye-opening and the development of the retinogeniculate pathway Neuron 36 2002 869 879
26. C.J. Akerman, M.S. Grubb, and I.D. Thompson Spatial and temporal properties of visual responses in the thalamus of the developing ferret J Neurosci 24 2004 170 182. The authors use a combination of simple and naturalistic visual stimuli to quantitatively characterize through-the-eyelid response properties of neonatal ferret thalamic neurons. The dataset define the temporal and spatial limits of vision during this period of development, with implications for the effects of the earliest possible experience on sensory system maturation. Thalamic neurons, for example, can detect spatial structure in naturalistic stimuli presented through the closed lids. This capability might be important in the development of single cell response properties in visual cortex before eye opening.
27. N. Tian, and D.R. Copenhagen Visual stimulation is required for refinement of ON and OFF pathways in postnatal retina Neuron 39 2003 85 96. This study shows that early visual experience, previously thought to leave the retina unaffected, has an important role in the development of on and off retinal pathways. As assessed by in vitro recording and single-cell morphology, the proportion of RGCs with both on and off inputs decreases dramatically in the second to fourth postnatal weeks in mice. This decrease is completely prevented, however, if mice are dark-reared to prevent visual experience from birth.
28. R.J. Wingate, and I.D. Thompson Targeting and activity-related dendritic modification in mammalian retinal ganglion cells J Neurosci 14 1994 6621 6637
29. E. Sernagor, and N.M. Grzywacz Influence of spontaneous activity and visual experience on developing retinal receptive fields Curr Biol 6 1996 1503 1508
30. J. Fulford, S.H. Vadeyar, S.H. Dodampahala, R.J. Moore, P. Young, P.N. Baker, D.K. James, and P.A. Gowland Fetal brain activity in response to a visual stimulus Hum Brain Mapp 20 2003 239 245. Functional magnetic resonance imaging (fMRI) was used by the authors to map human foetal brain activity in response to a bright light source of constant intensity presented to the maternal abdomen. In 5/8 subjects, the presence of bright visual stimulation was accompanied by significant cortical activation. Interestingly, this activation was in frontal rather than occipital cortex. Although mapping was not of sufficient resolution to detect activity in subcortical structures, these data imply that external sensory experience can activate retinal, subcortical and cortical elements of the visual pathway while humans are still in the womb.
31. H. Eswaran, J. Wilson, H. Preissl, S. Robinson, J. Vrba, P. Murphy, D. Rose, and C. Lowery Magnetoencephalographic recordings of visual evoked brain activity in the human fetus Lancet 360 2002 779 780
32. L. Kiorpes, C. Tang, M.J. Hawken, and J.A. Movshon Ideal observer analysis of the development of spatial contrast sensitivity in macaque monkeys J Vis 3 2003 630 641. The authors construct an ideal observer model for the infant macaque visual system using previously published and newly obtained data concerning optics and retinal morphology. The ideal model shows some improvement in spatial contrast sensitivity up to 4 weeks of age, but very little thereafter. By contrast, behavioural data from young monkeys show that sensitivity continues to improve extensively after the first 4 postnatal weeks. This late improvement cannot therefore be caused by changes in non-neural sensory structures; instead, it must be due to alterations in developing neuronal circuitry.
33. T.D. Mrsic-Flogel, J.W. Schnupp, and A.J. King Acoustic factors govern developmental sharpening of spatial tuning in the auditory cortex Nat Neurosci 6 2003 981 988. The authors provide a demonstration that sensory experience need not contribute to the postnatal development of neuronal response properties. Using a virtual acoustic system to present 'spatially localized' auditory stimuli, these authors let neonatal ferrets listen as if their outer ears were adult-like. This non-neuronal change in the filtering of sensory experience was sufficient to make spatially restricted responses in primary auditory cortex as good as those of adult neurons. Development of spatial processing in the auditory cortex might therefore be unrelated to sensory experience and instead be entirely due to changes in the structure of the outer ear.
34. J.C. Horton, and D.R. Hocking An adult-like pattern of ocular dominance columns in striate cortex of newborn monkeys prior to visual experience J Neurosci 16 1996 1791 1807
35. J.C. Crowley, and L.C. Katz Early development of ocular dominance columns Science 290 2000 1321 1324
36. Y. Fregnac, and M. Imbert Early development of visual cortical cells in normal and dark-reared kittens: relationship between orientation selectivity and ocular dominance J Physiol 278 1978 27 44
37. B. Chapman, and M.P. Stryker Development of orientation selectivity in ferret visual cortex and effects of deprivation J Neurosci 13 1993 5251 5262
38. M.C. Crair, D.C. Gillespie, and M.P. Stryker The role of visual experience in the development of columns in cat visual cortex Science 279 1998 566 570
39. E.F. Chang, and M.M. Merzenich Environmental noise retards auditory cortical development Science 300 2003 498 502. Abnormal experience can alter the functional development of auditory cortex. The authors raised rat pups in the presence of continuous moderately loud white noise from before the onset of hearing (P7) and found that there was some developmental improvement in tonotopicity and frequency selectivity in the rat primary auditory cortex. However, this improvement was delayed relative to normally reared animals, and the subjects never attained normal adult-like performance. Noise-rearing also extended the critical period for the effects of pure tone experience.
40. N. Mayer, J.M. Herrmann, and T. Geisel Shaping of receptive fields in the visual cortex during retinal maturation J Comput Neurosci 15 2003 307 320
41. G.L. Miller, and E.I. Knudsen Adaptive plasticity in the auditory thalamus of juvenile barn owls J Neurosci 23 2003 1059 1065. Altered auditory experience known to affect the tuning properties of forebrain neurons has equally strong effects in the auditory thalamus, but no effects in the midbrain inferior colliculus, which suggests a thalamic locus of effect. The authors fitted juvenile barn owls with a filtering device that rendered stimulus interaural time differences (ITDs) frequency dependent. In these owls, but not in normal animals, ITD tuning in auditory thalamic neurons became frequency dependent.
42. A.J. King, J.W. Schnupp, and I.D. Thompson Signals from the superficial layers of the superior colliculus enable the development of the auditory space map in the deeper layers J Neurosci 18 1998 9394 9408
43. T.P. Doubell, I. Skaliora, J. Baron, and A.J. King Functional connectivity between the superficial and deeper layers of the superior colliculus: an anatomical substrate for sensorimotor integration J Neurosci 23 2003 6596 6607
44. A. Waldenstrom, J. Thelin, E. Thimansson, A. Levinsson, and J. Schouenborg Developmental learning in a pain-related system: evidence for a cross-modality mechanism J Neurosci 23 2003 7719 7725. The authors provide a description of an unusual experience-dependent developmental phenomenon. Correct withdrawal responses to painful heat develop over the third postnatal week in rats. This development is not affected if painful stimuli are prevented through mechanical protection and analgesic cream, nor if hair-follicle-dependent somatosensory stimulation is abolished over this period. The reflex fails to develop correctly, however, if both painful and somatosensory stimulation are prevented. This suggests that, in the absence of appropriate noxious stimuli, an important reflex can still develop properly under the guidance of non-noxious somatosensory experience.
45. G.T. Prusky, and R.M. Douglas Developmental plasticity of mouse visual acuity Eur J Neurosci 17 2003 167 173
46. D.E. Mitchell, P.C. Kind, F. Sengpiel, and K. Murphy Brief daily periods of binocular vision prevent deprivation-induced acuity loss Curr Biol 13 2003 1704 1708
47. L.E. White, D.M. Coppola, and D. Fitzpatrick The contribution of sensory experience to the maturation of orientation selectivity in ferret visual cortex Nature 411 2001 1049 1052
48. A. Bartoletti, P. Medini, N. Berardi, and L. Maffei Environmental enrichment prevents effects of dark-rearing in the rat visual cortex Nat Neurosci 7 2004 215 216. The authors describe a fascinating rescue of visual deprivation effects using a non-visual manipulation. Dark-rearing rats from birth normally produces decreased visual acuity in primary visual cortex and an extension of the critical period for monocular deprivation. Both of these effects, however, were completely prevented when dark-reared rats grew up in an enriched environment comprising a large area full of assorted objects. This dramatic finding suggests that dark-rearing does not affect visual cortical development by preventing visual patterning of cortical activity, but rather by providing a level of cortical activity which can be compensated for by a more stimulating (non-visual) environment.
49. ••] might act by increasing levels of cortical neurotrophins.
50. E.S. Ruthazer, C.J. Akerman, and H.T. Cline Control of axon branch dynamics by correlated activity in vivo Science 301 2003 66 70. The authors present a study showing that activity patterns can regulate axonal growth in the developing Xenopus retinotectal system. In a normally completely crossed projection, axons from both eyes were induced to invade a single optic tectum by ablation of its counterpart in the opposite hemisphere. In this preparation axons from the two eyes are presumed not to differ in terms of either molecular properties or levels of activity, but they still form ocular-specific domains, which suggests that patterns of electrical activity (higher correlations within eyes than between eyes) guide axonal growth. This study employed chronic in vivo imaging of single axons to show that new axon branches are added regardless of the inputs dominating the territory they extend into. Branches are preferentially retracted, however, from tectal territories dominated by inputs from the opposite eye. Patterns of activity therefore shape retinotectal development by directing the retraction of initially diffuse axonal branches.
51. M. Constantine-Paton, H.T. Cline, and E. Debski Patterned activity, synaptic convergence, and the NMDA receptor in developing visual pathways Annu Rev Neurosci 13 1990 129 154
52. A. Antonini, and M.P. Stryker Rapid remodelling of axonal arbors in the visual cortex Science 260 1993 1819 1821
53. E. Foeller, and D.E. Feldman Synaptic basis for developmental plasticity in somatosensory cortex Curr Opin Neurobiol 14 2004 89 95. The authors present an excellent review of synaptic mechanisms involved in barrel cortex plasticity.
54. K.J. Bender, J. Rangel, and D.E. Feldman Development of columnar topography in the excitatory layer 4 to layer 2/3 projection in rat barrel cortex J Neurosci 23 2003 8759 8770
55. G.M. Shepherd, T.A. Pologruto, and K. Svoboda Circuit analysis of experience-dependent plasticity in the developing rat barrel cortex Neuron 38 2003 277 289. By combining in vitro electrophysiological recordings of single layer 2/3 barrel cortex neurons with systematic and selective activation of surrounding cells by uncaging glutamate (laser-scanning photo stimulation), these authors demonstrate the effects of sensory deprivation on cortical synaptic networks. Trimming all facial whiskers from P9 to P14-16 in rats causes layer 2/3 neurons situated above barrels to receive inputs from a wider than normal range of layer 4 cells, while layer 2/3 neurons situated above barrel septa receive more input from the layer 4 cells directly beneath them.
56. C.B. Allen, T. Celikel, and D.E. Feldman Long-term depression induced by sensory deprivation during cortical map plasticity in vivo Nat Neurosci 6 2003 291 299. The authors give an elegant demonstration of one mechanism for experience-dependent plasticity in the cortex. Somatosensory deprivation by whisker plucking in P12-P30 rats decreased local field potentials and synaptic potentials in layer 2/3 neurons recorded in ex vivo barrel cortex slices. These changes depressed transmission at layer 4 to layer 2/3 synapses and occluded LTD induction in vitro, which suggests that LTD underlies the reduction of cortical responses to deprived whiskers. Furthermore, in vivo recordings show that virtual whisker deprivation produces exactly the right pattern of activity in layers 4 and 2/3 to produce LTD in the layer 4 to layer 2/3 synapse.
57. T. Takahashi, K. Svoboda, and R. Malinow Experience strengthening transmission by driving AMPA receptors into synapses Science 299 2003 1585 1588. The authors use state-of-the-art molecular techniques to show that sensory experience is accompanied by the insertion of specific glutamate receptor subunits into cell membranes. The AMPA receptor subunit GluR1 appears at synapses only after NMDA receptor-dependent LTP. Using a virus to increase expression of GluR1 in particular fluorescently labelled cells in layer 2/3 of rat barrel cortex produced increased rectification of AMPA receptor-mediated currents, indicative of synaptic incorporation of the ectopic subunits. This increased rectification, however, did not occur if whiskers were trimmed to prevent sensory experience in the 3 days before recording. In addition, blocking the synaptic insertion of GluR1 subunits with a viral vector caused a decrease in synaptic transmission between layer 4 and layer 2/3 cells in normal animals, but not in rats recently deprived of whisker stimulation. Normal somatosensory experience therefore appears necessary to strengthen layer 4 to layer 2/3 transmission through the synaptic incorporation of GluR1 subunits.
58. I. Ehrlich, and R. Malinow Postsynaptic density 95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity J Neurosci 24 2004 916 927
59. ••], this is compelling evidence for a role for LTD in experience-dependent mechanisms of cortical development.
60. F. Engert, H.W. Tao, L.I. Zhang, and M.M. Poo Moving visual stimuli rapidly induce direction sensitivity of developing tectal neurons Nature 419 2002 470 475
61. Q. Zhou, H.W. Tao, and M.M. Poo Reversal and stabilization of synaptic modifications in a developing visual system Science 300 2003 1953 1957. Amongst other findings, the authors provide a lovely demonstration that structured visual experience can change synaptic strengths in the developing brain, and that unstructured visual experience, or even spontaneous activity, can then reverse those changes. Synapses between RGCs and tectal neurons in developing tadpoles could become strengthened or weakened in vivo following repetitive visual stimulation with a moving bar. However, following this structured visual experience with a series of random light flashes onto the retina, or a period of spontaneous activity, rapidly reversed those synaptic strength changes. Activity patterns produced by early experience are therefore able to instruct changes in connection strengths between developing sensory neurons.
62. A subunits have been mutated. Benzodiazepine agonists failed to: first, affect ocular dominance plasticity in the α1 line only, and second, modulate immature firing rates in the α2 line only. Different inhibitory neuronal circuits appear to play different parts in the development of visual cortex.
63. ••]; Figure 3b) and also decreases the correlation between layer 4 and layer 2/3 activity. Modeling these changes shows that alterations in the mean firing rate are not sufficient to account for the LTD observed between layers 4 and layers 2/3 but that the changes in timing and the decorrelation are.
64. C.C.H. Petersen, M. Brecht, T.T.G. Hahn, and B. Sakmann Synaptic changes in layer 2/3 underlying map plasticity of developing barrel cortex Science 304 2004 739 742. An impressive range of techniques is used in this study to investigate connectivity changes in barrel cortex following asymmetric whisker trimming. Whisker rows A-C are trimmed daily from P7 to P17 or more and the connections of whisker D-barrels to adjacent C-barrels (deprived) and E-barrels (non-deprived) examined. in vivo voltage sensitive dye (VSD) studies show that, following stimulation of D-whiskers, the early cortical signal is unaffected by trimming (it remains restricted to D-barrels) but the later signal becomes biased towards E-barrels. VSD in cortical slices confirms this asymmetry and locates it to layers 2/3. Recordings in vivo from layer 2/3 neurons in C- or E-barrels show that the post-synaptic potentials (PSPs) elicited by stimulating D-whiskers are dramatically affected by trimming: PSPs in C-barrel neurons fall by more than half and in E-barrel neurons increase by 50%. Triple-recordings in slice studies show that the PSP changes are associated with first, a decrease in unitary PSP size but not in the probability of connection for neuron pairs in barrels D and C, and second, an increase in the probability of connection but no change in unitary PSP size for neuron pairs in barrels D and E. Finally, after trimming, there are many more axon terminals from D-barrel neurons in E-barrels than in C-barrels. It will be interesting to determine to what extent these changes reflect the shaping of initially exuberant projections or induction of new connections.
65. M. Maravall, I.Y.Y. Koh, W.B. Lindquist, and K. Svoboda Experience-dependent changes in basal dendritic branching of layer 2/3 pyramidal neurons during a critical period for developmental plasticity in rat barrel cortex Cerebral Cortex 14 2004 655 664. The authors investigate changes in morphology of the basal dendrites, which receive most of the input from layer 4. Between postnatal days 9 and 20 (P9-P20), there is no change in the organization of primary dendrites but secondary dendrites change: analysis of the location and of branch tips suggest that secondary dendrites are both added and retracted. Sholl analyses imply increased dendritic distribution across the arbor. Clipping of all whiskers from P9 prevented the changes in secondary dendrites.
66. D.-J. Zou, P. Feinstein, A.L. Rivers, G.A. Mathews, A. Kim, C.A. Greer, P. Mombaerts, and S. Firestein Postnatal refinement of peripheral olfactory projections Science 2004 [Epub ahead of print]. β-gal tagged odorant receptors (ORs) are used by the authors to follow the mapping of olfactory sensory neurons (OSNs) onto olfactory glomeruli. Glomeruli are clearly defined by axonal projections at postnatal day 10 (P10) but the innervation pattern of axons carrying individual ORs is much more diffuse at this age than in the adult. More glomeruli are innervated by a given type of OSN and many receive convergent input from different populations of OSNs. The projection refines gradually, with a time course that varies according to the OSN type. The adult pattern is attained by P20 for axons carrying OR M72 but not until P60 by those carrying OR M71. Fascinatingly, sensory deprivation (unilateral naris closure) at P0 prevents the elimination of convergent projections. Later deprivation reveals that the sensitive period is OR-dependent (P15 for axons carrying M72, P25 for M71). The authors speculate that refinement is achieved by selective cell death.
67. C.R. Yu, J. Power, G. Barnea, S. O'Donnell, H.E. Brown, J. Osborne, R. Axel, and J.A. Gogos Spontaneous neural activity is required for the establishment and maintenance of the olfactory sensory map Neuron 42 2004 553 566. The authors present a carefully controlled and imaginative study that uses multiple experimental approaches to investigate the dependence of the olfactory map formation on transmitter release and/or neuronal activity in OSNs. Knock-in of the tetanus toxin light chain was used to inhibit synaptic release either in all OSNs or in a subset expressing the P2 odorant receptor. When all OSNs are inhibited, glomerular targeting is normal, based on the behaviour of P2-containing or of MOR28-containing axons. Restricting the tetanus toxin to a subset of OSNs (P2-containing) results in disturbed targeting: many P2 axons fail to converge on the appropriate glomeruli and, eventually, these OSNs die. Targeting can also be disrupted by conditional tetanus toxin expression after the glomeruli have been formed. An alternative approach used over-expression of the inward rectifying potassium channel Kir2.1 to silence neuronal activity in OSNs. Global silencing delays innervation of the olfactory bulb and also variably disrupts the precision of OSN targeting (P2-axons are more disrupted than MOR28-axons). Restricted silencing (to the P2-containing population) early in development greatly decreases the number of P2-axons entering the olfactory bulb. Restricted silencing after map formation (P21), did not immediately destabilise the map but eventually leads to a loss of P2-containing OSNs. Is activity anything more than permissive in the system?