Evidence for active synapse formation or altered postsynaptic metabolism in visual cortex of rats reared in complex environments.

GABAergic interneurons are proposed to be critical for early activity and synapse formation by directly exciting, rather than inhibiting, neurons in developing hippocampus and neocortex. However, the role of GABAergic neurons in the generation of neonatal network activity has not been tested in vivo, and recent studies have challenged the excitatory nature of early GABA. By locally manipulating interneuron activity in unanesthetized neonatal mice, we show that GABAergic neurons are excitatory in CA1 hippocampus at postnatal day 3 (P3) and are responsible for most of the spontaneous firing of pyramidal cells at that age. Hippocampal interneurons become inhibitory by P7, whereas visual cortex interneurons are already inhibitory by P3 and remain so throughout development. These regional and age-specific differences are the result of a change in chloride reversal potential, because direct activation of light-gated anion channels in glutamatergic neurons drives CA1 firing at P3, but silences it at P7 in CA1, and at all ages in visual cortex. This study in the intact brain reveals that GABAergic interneuron excitation is essential for network activity in neonatal hippocampus and confirms that visual cortical interneurons are inhibitory throughout early postnatal development.

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Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.97.12.6728 ◽

2000 ◽

Vol 97 (12) ◽

pp. 6728-6733 ◽

Cited By ~ 840

Author(s):

T. C. Holmes ◽

S. de Lacalle ◽

X. Su ◽

G. Liu ◽

A. Rich ◽

...

Keyword(s):

Neurite Outgrowth ◽

Synapse Formation ◽

Self Assembling ◽

Active Synapse ◽

Peptide Scaffolds

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Precise levels of nectin-3 are required for proper synapse formation in postnatal visual cortex

Neural Development ◽

10.1186/s13064-020-00150-w ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Johanna Tomorsky ◽

Philip R. L. Parker ◽

Chris Q. Doe ◽

Cristopher M. Niell

Keyword(s):

Visual Cortex ◽

Dendritic Spine ◽

Cortical Neurons ◽

Synapse Formation ◽

Ocular Dominance ◽

Developmental Time ◽

Basal Dendrites ◽

Layer 2 ◽

Eye Opening ◽

Visual Cortical

Abstract Background Developing cortical neurons express a tightly choreographed sequence of cytoskeletal and transmembrane proteins to form and strengthen specific synaptic connections during circuit formation. Nectin-3 is a cell-adhesion molecule with previously described roles in synapse formation and maintenance. This protein and its binding partner, nectin-1, are selectively expressed in upper-layer neurons of mouse visual cortex, but their role in the development of cortical circuits is unknown. Methods Here we block nectin-3 expression (via shRNA) or overexpress nectin-3 in developing layer 2/3 visual cortical neurons using in utero electroporation. We then assay dendritic spine densities at three developmental time points: eye opening (postnatal day (P)14), one week following eye opening after a period of heightened synaptogenesis (P21), and at the close of the critical period for ocular dominance plasticity (P35). Results Knockdown of nectin-3 beginning at E15.5 or ~ P19 increased dendritic spine densities at P21 or P35, respectively. Conversely, overexpressing full length nectin-3 at E15.5 decreased dendritic spine densities when all ages were considered together. The effects of nectin-3 knockdown and overexpression on dendritic spine densities were most significant on proximal secondary apical dendrites. Interestingly, an even greater decrease in dendritic spine densities, particularly on basal dendrites at P21, was observed when we overexpressed nectin-3 lacking its afadin binding domain. Conclusion These data collectively suggest that the proper levels and functioning of nectin-3 facilitate normal synapse formation after eye opening on apical and basal dendrites in layer 2/3 of visual cortex.

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Plasticity of GFAP-immunoreactive astrocyte size and number in visual cortex of rats reared in complex environments

Brain Research ◽

10.1016/0006-8993(91)90517-y ◽

1991 ◽

Vol 540 (1-2) ◽

pp. 273-278 ◽

Cited By ~ 101

Author(s):

Anita M. Sirevaag ◽

William T. Greenough

Keyword(s):

Visual Cortex ◽

Complex Environments

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Precise levels of Nectin-3 and an interaction with Afadin are required for proper synapse formation in postnatal visual cortex

10.1101/870691 ◽

2019 ◽

Author(s):

Johanna Tomorsky ◽

Philip R. L. Parker ◽

Chris Q. Doe ◽

Cristopher M. Niell

Keyword(s):

Visual Cortex ◽

Dendritic Spine ◽

Cortical Neurons ◽

Synapse Formation ◽

Ocular Dominance ◽

Developmental Time ◽

Ocular Dominance Plasticity ◽

Layer 2 ◽

Eye Opening ◽

Visual Cortical

AbstractBackgroundDeveloping cortical neurons express a tightly choreographed sequence of cytoskeletal and transmembrane proteins to form and strengthen specific synaptic connections during circuit formation. Nectin-3 is a cell-adhesion molecule with previously described roles in synapse formation and maintenance. This protein and its binding partner, Nectin-1, are selectively expressed in upper-layer neurons of mouse visual cortex, but their role in the development of cortical circuits is unknown.MethodsHere we block Nectin-3 expression (via shRNA) or overexpress Nectin-3 in developing layer 2/3 visual cortical neurons using in utero electroporation. We then assay dendritic spine densities at three developmental time points: eye opening (postnatal day (P)14), one week following eye opening after a period of heightened synaptogenesis (P21), and at the close of the critical period for ocular dominance plasticity (P35).ResultsKnockdown of Nectin-3 beginning at E15.5 or ∼P19 increased dendritic spine densities at P21 or P35, respectively. Conversely, overexpressing full length Nectin-3 at E15.5 led to decreased dendritic spine densities when all ages were considered together. Interestingly, an even greater decrease in dendritic spine densities, particularly at P21, was observed when we overexpressed Nectin-3 lacking its Afadin binding domain, indicating Afadin may facilitate spine morphogenesis after eye opening.ConclusionThese data collectively suggest that the proper levels of Nectin-3, as well as the interaction of Nectin-3 with Afadin, facilitate normal synapse formation after eye opening in layer 2/3 visual cortical neurons.

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Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds

The Excitement of Discovery: Selected Papers of Alexander Rich - Series in Structural Biology ◽

10.1142/9789813272682_0054 ◽

2018 ◽

pp. 367-372

Author(s):

Todd C. Holmes ◽

Sonsoles de Lacalle ◽

Xing Su ◽

Guosong Liu ◽

Alexander Rich ◽

...

Keyword(s):

Neurite Outgrowth ◽

Synapse Formation ◽

Self Assembling ◽

Active Synapse ◽

Peptide Scaffolds

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Vision is Required for Cell Type Specification in the Visual Cortex

10.1101/2021.08.10.455824 ◽

2021 ◽

Author(s):

Sarah Cheng ◽

Salwan Butrus ◽

Vincent Xu ◽

Srikant Sagireddy ◽

Liming Tan ◽

...

Keyword(s):

Visual Cortex ◽

Synapse Formation ◽

Cortical Development ◽

Cortical Cell ◽

Cell Types ◽

Postnatal Life ◽

Neuronal Types ◽

Single Nucleus ◽

Eye Opening ◽

Mouse Visual Cortex

The role of postnatal experience in mammalian cortical development, while long appreciated, is poorly understood at the resolution of cell types. To explore this issue, we used single-nucleus RNA-sequencing to profile the mouse visual cortex at different times in postnatal life with and without visual experience. The identities of glutamatergic cell types in upper layers (L) (L2/3/4) were established following eye opening. L2/3 cell types formed a spatial continuum, defined by the graded expression of ~200 genes that included candidates associated with synapse formation and axon projection specificity. These patterns required visual input for both their establishment and maintenance. By contrast to upper-layer glutamatergic neurons, the remaining neuronal and non-neuronal types were established in a vision-independent fashion. Our results demonstrate that vision acts preferentially in the specification of cortical cell types and provide a framework for exploring experience-dependent cortical development at the cellular and molecular level.

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