Silent synapses persist into adulthood in layer 2/3 pyramidal neurons of visual cortex in dark-reared mice

Funahashi, Rie; Maruyama, Takuro; Yoshimura, Yumiko; Komatsu, Yukio

doi:10.1152/jn.00912.2012

Cited by 33 publications

(36 citation statements)

References 67 publications

(95 reference statements)

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“…In either the GFP-positive or GFP-negative neurons in chimeric mice, the resting membrane potential and threshold of action potential generation did not change from P13–16 to P18–20 (Additional file 3: Figure S3E, F). The input resistance decreased during this developmental period, consistent with a previous study (Additional file 3: Figure S3G) [36]. …”

Section: Resultssupporting

confidence: 91%

Establishment of high reciprocal connectivity between clonal cortical neurons is regulated by the Dnmt3b DNA methyltransferase and clustered protocadherins

et al. 2016

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BackgroundThe specificity of synaptic connections is fundamental for proper neural circuit function. Specific neuronal connections that underlie information processing in the sensory cortex are initially established without sensory experiences to a considerable extent, and then the connections are individually refined through sensory experiences. Excitatory neurons arising from the same single progenitor cell are preferentially connected in the postnatal cortex, suggesting that cell lineage contributes to the initial wiring of neurons. However, the postnatal developmental process of lineage-dependent connection specificity is not known, nor how clonal neurons, which are derived from the same neural stem cell, are stamped with the identity of their common neural stem cell and guided to form synaptic connections.ResultsWe show that cortical excitatory neurons that arise from the same neural stem cell and reside within the same layer preferentially establish reciprocal synaptic connections in the mouse barrel cortex. We observed a transient increase in synaptic connections between clonal but not nonclonal neuron pairs during postnatal development, followed by selective stabilization of the reciprocal connections between clonal neuron pairs. Furthermore, we demonstrate that selective stabilization of the reciprocal connections between clonal neuron pairs is impaired by the deficiency of DNA methyltransferase 3b (Dnmt3b), which determines DNA-methylation patterns of genes in stem cells during early corticogenesis. Dnmt3b regulates the postnatal expression of clustered protocadherin (cPcdh) isoforms, a family of adhesion molecules. We found that cPcdh deficiency in clonal neuron pairs impairs the whole process of the formation and stabilization of connections to establish lineage-specific connection reciprocity.ConclusionsOur results demonstrate that local, reciprocal neural connections are selectively formed and retained between clonal neurons in layer 4 of the barrel cortex during postnatal development, and that Dnmt3b and cPcdhs are required for the establishment of lineage-specific reciprocal connections. These findings indicate that lineage-specific connection reciprocity is predetermined by Dnmt3b during embryonic development, and that the cPcdhs contribute to postnatal cortical neuron identification to guide lineage-dependent synaptic connections in the neocortex.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-016-0326-6) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 91%

Establishment of high reciprocal connectivity between clonal cortical neurons is regulated by the Dnmt3b DNA methyltransferase and clustered protocadherins

et al. 2016

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“…2). It is known that silent synapse numbers decrease during critical periods (13,25). Our results show the reverse correlation that lack of silent synapse maturation correlates with the persistence of juvenile-like ODP in V1, indicating that by preventing silent synapse maturation, the termination of the CP for juvenilelike ODP is prevented as well.…”

Section: Discussionmentioning

confidence: 44%

“…Our results show the reverse correlation that lack of silent synapse maturation correlates with the persistence of juvenile-like ODP in V1, indicating that by preventing silent synapse maturation, the termination of the CP for juvenilelike ODP is prevented as well. Similarly, dark rearing from birth preserves juvenile-like ODP (60) and results in an elevated number of silent synapses (25). However, the retardation of silent synapse maturation and critical period closure have not been causally linked.…”

Section: Discussionmentioning

confidence: 99%

“…They are functionally dormant but can evolve into fully transmitting synapses by experience-dependent insertion of AMPARs, a plasticity process thought to occur frequently in developing cortices (10). Although they appear as the ideal synaptic substrate for CP plasticity and their maturation correlates with sensory experience (10,25), it has not been experimentally tested whether maturation of silent synapses indeed causes the termination of critical periods. This conceptual model contrasts with the current view that increased local inhibition and the expression of plasticity brakes ends critical periods (18)(19)(20)26).…”

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confidence: 99%

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Progressive maturation of silent synapses governs the duration of a critical period

Huang

Stodieck

Goetze

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

100

172

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During critical periods, all cortical neural circuits are refined to optimize their functional properties. The prevailing notion is that the balance between excitation and inhibition determines the onset and closure of critical periods. In contrast, we show that maturation of silent glutamatergic synapses onto principal neurons was sufficient to govern the duration of the critical period for ocular dominance plasticity in the visual cortex of mice. Specifically, postsynaptic density protein-95 (PSD-95) was absolutely required for experience-dependent maturation of silent synapses, and its absence before the onset of critical periods resulted in lifelong juvenile ocular dominance plasticity. Loss of PSD-95 in the visual cortex after the closure of the critical period reinstated silent synapses, resulting in reopening of juvenile-like ocular dominance plasticity. Additionally, silent synapse-based ocular dominance plasticity was largely independent of the inhibitory tone, whose developmental maturation was independent of PSD-95. Moreover, glutamatergic synaptic transmission onto parvalbumin-positive interneurons was unaltered in PSD-95 KO mice. These findings reveal not only that PSD-95-dependent silent synapse maturation in visual cortical principal neurons terminates the critical period for ocular dominance plasticity but also indicate that, in general, once silent synapses are consolidated in any neural circuit, initial experience-dependent functional optimization and critical periods end.

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“…Excitatory synapses of dark-reared cortical neurons at P20–24 and P50 have the low AMPA/NMDA receptor ratio normally seen at eye opening (Funahashi et al, 2013). Not only AMPA receptor currents remain low, also NMDA receptor currents are impaired in dark-reared cortex (Funahashi et al, 2013). Dark rearing also impairs the development of GABAergic inhibition.…”

Section: Discussionmentioning

confidence: 99%

A period of structural plasticity at the axon initial segment in developing visual cortex

et al. 2014

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Cortical networks are shaped by sensory experience and are most susceptible to modifications during critical periods characterized by enhanced plasticity at the structural and functional level. A system particularly well-studied in this context is the mammalian visual system. Plasticity has been documented for the somatodendritic compartment of neurons in detail. A neuronal microdomain not yet studied in this context is the axon initial segment (AIS) located at the proximal axon segment. It is a specific electrogenic axonal domain and the site of action potential (AP) generation. Recent studies showed that structure and function of the AIS can be dynamically regulated. Here we hypothesize that the AIS shows a dynamic regulation during maturation of the visual cortex. We therefore analyzed AIS length development from embryonic day (E) 12.5 to adulthood in mice. A tri-phasic time course of AIS length remodeling during development was observed. AIS first appeared at E14.5 and increased in length throughout the postnatal period to a peak between postnatal day (P) 10 to P15 (eyes open P13–14). Then, AIS length was reduced significantly around the beginning of the critical period for ocular dominance plasticity (CP, P21). Shortest AIS were observed at the peak of the CP (P28), followed by a moderate elongation toward the end of the CP (P35). To test if the dynamic maturation of the AIS is influenced by eye opening (onset of activity), animals were deprived of visual input before and during the CP. Deprivation for 1 week prior to eye opening did not affect AIS length development. However, deprivation from P0 to 28 and P14 to 28 resulted in AIS length distribution similar to the peak at P15. In other words, deprivation from birth prevents the transient shortening of the AIS and maintains an immature AIS length. These results are the first to suggest a dynamic maturation of the AIS in cortical neurons and point to novel mechanisms in the development of neuronal excitability.

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Silent synapses persist into adulthood in layer 2/3 pyramidal neurons of visual cortex in dark-reared mice

Cited by 33 publications

References 67 publications

Establishment of high reciprocal connectivity between clonal cortical neurons is regulated by the Dnmt3b DNA methyltransferase and clustered protocadherins

Establishment of high reciprocal connectivity between clonal cortical neurons is regulated by the Dnmt3b DNA methyltransferase and clustered protocadherins

Progressive maturation of silent synapses governs the duration of a critical period

A period of structural plasticity at the axon initial segment in developing visual cortex

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