Dynamics of nascent and active zone ultrastructure as synapses enlarge during long‐term potentiation in mature hippocampus

Bell, Maria Elizabeth; Bourne, Jennifer N.; Chirillo, Michael A.; Mendenhall, John M.; Kuwajima, Masaaki; Harris, Kristen M.

doi:10.1002/cne.23646

Cited by 63 publications

(104 citation statements)

References 149 publications

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“…tion of silent synaptic regions during LTP (Bell et al 2014). Both nascent and active zones of mature hippocampal synapses have a distinct PSD, but unlike the active zone, the presynaptic side of a nascent zone lacks synaptic vesicles (Fig.…”

Section: Molecular Mechanisms Underlying the Structural Changes That mentioning

confidence: 99%

“…Both nascent and active zones of mature hippocampal synapses have a distinct PSD, but unlike the active zone, the presynaptic side of a nascent zone lacks synaptic vesicles (Fig. 9A-D) (Spacek and Harris 1998;Bell et al 2014). Immunogold labeling has revealed glutamate receptors at the edges of cultured hippocampal synapses (Nair et al 2013) and in nascent zones of mature hippocampal synapses (Bell et al 2014).…”

Section: Molecular Mechanisms Underlying the Structural Changes That mentioning

confidence: 99%

“…9A-D) (Spacek and Harris 1998;Bell et al 2014). Immunogold labeling has revealed glutamate receptors at the edges of cultured hippocampal synapses (Nair et al 2013) and in nascent zones of mature hippocampal synapses (Bell et al 2014). However, stochastic modeling suggests that falloff in glutamate concentration in the synaptic cleft reduces the probability of glutamate receptor activation from 0.4 at the center of a release site to 0.1 just 200 nm away (Franks et al 2002(Franks et al , 2003.…”

Section: Molecular Mechanisms Underlying the Structural Changes That mentioning

confidence: 99%

“…However, stochastic modeling suggests that falloff in glutamate concentration in the synaptic cleft reduces the probability of glutamate receptor activation from 0.4 at the center of a release site to 0.1 just 200 nm away (Franks et al 2002(Franks et al , 2003. The average distance from vesicles docked at active zones to adjacent nascent zones was 200 nm; hence, the conversion of nascent zones to functional active zones via recruitment of presynaptic vesicles may constitute the initial phase of LTP (Bell et al 2014). This conversion could be facilitated by the insertion of DCVs at existing nascent zones, as DCVs moved into more presynaptic boutons by 5 min following the induction of LTP, and by 30 min, DCV frequency had returned to control levels, as additional presynaptic vesicles were recruited to nascent zones (Bell et al 2014).…”

Section: Molecular Mechanisms Underlying the Structural Changes That mentioning

confidence: 99%

“…The average distance from vesicles docked at active zones to adjacent nascent zones was 200 nm; hence, the conversion of nascent zones to functional active zones via recruitment of presynaptic vesicles may constitute the initial phase of LTP (Bell et al 2014). This conversion could be facilitated by the insertion of DCVs at existing nascent zones, as DCVs moved into more presynaptic boutons by 5 min following the induction of LTP, and by 30 min, DCV frequency had returned to control levels, as additional presynaptic vesicles were recruited to nascent zones (Bell et al 2014). By 2 h, there were fewer small dendritic spines relative to control stimulation in the same slices (Bourne and Harris 2011), and both nascent and active zones were enlarged, potentially, in preparation for synapses to undergo further plasticity (Fig.…”

Section: Molecular Mechanisms Underlying the Structural Changes That mentioning

confidence: 99%

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Structural Components of Synaptic Plasticity and Memory Consolidation

Bailey

Kandel

Harris

2015

Cold Spring Harb Perspect Biol

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Consolidation of implicit memory in the invertebrate Aplysia and explicit memory in the mammalian hippocampus are associated with remodeling and growth of preexisting synapses and the formation of new synapses. Here, we compare and contrast structural components of the synaptic plasticity that underlies these two distinct forms of memory. In both cases, the structural changes involve time-dependent processes. Thus, some modifications are transient and may contribute to early formative stages of long-term memory, whereas others are more stable, longer lasting, and likely to confer persistence to memory storage. In addition, we explore the possibility that trans-synaptic signaling mechanisms governing de novo synapse formation during development can be reused in the adult for the purposes of structural synaptic plasticity and memory storage. Finally, we discuss how these mechanisms set in motion structural rearrangements that prepare a synapse to strengthen the same memory and, perhaps, to allow it to take part in other memories as a basis for understanding how their anatomical representation results in the enhanced expression and storage of memories in the brain.

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Section: Molecular Mechanisms Underlying the Structural Changes That mentioning

confidence: 99%

Section: Molecular Mechanisms Underlying the Structural Changes That mentioning

confidence: 99%

Section: Molecular Mechanisms Underlying the Structural Changes That mentioning

confidence: 99%

Section: Molecular Mechanisms Underlying the Structural Changes That mentioning

confidence: 99%

Section: Molecular Mechanisms Underlying the Structural Changes That mentioning

confidence: 99%

See 3 more Smart Citations

Structural Components of Synaptic Plasticity and Memory Consolidation

Bailey

Kandel

Harris

2015

Cold Spring Harb Perspect Biol

Self Cite

316

259

View full text Add to dashboard Cite

show abstract

Dendritic Spines

Kirk¹,

Harris²

2016

Encyclopedia of Life Sciences

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Dendritic spines are small protrusions from dendrites that host the majority of excitatory synapses in the central nervous system. Structurally, excitatory synapses located on dendritic spines are asymmetric, with a presynaptic bouton that contains round clear vesicles apposed to a postsynaptic density where glutamate receptors are anchored. Spines form biochemical compartments that can isolate activated signalling pathways that occur at one synapse from those at other synapses, thereby providing a way to enhance the specificity of connections between neurons in the brain. Structural changes of dendritic spines in response to stimulation facilitate changes in synaptic strength, and these changes are likely to underlie important higher brain functions such as learning and memory. Dysregulation of spine morphology is seen in several neurological disorders such as Alzheimer's disease and fragile X syndrome. Key Concepts Spines are the primary site of excitatory synapses. Smooth endoplasmic reticulum can form complex structures localized to large spines. The cytoskeleton of spines is mostly composed of actin. Trans‐synaptic adhesion molecules as well as proteins secreted from astroglia help stabilise synapses. Spines can act as small biochemical compartments. Spine structure is responsive to activity.

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Multiple roles of afadin in the ultrastructural morphogenesis of mouse hippocampal mossy fiber synapses

Sai

Wang

Kaito

et al. 2017

J of Comparative Neurology

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A hippocampal mossy fiber synapse, which is implicated in learning and memory, has a complex structure in which mossy fiber boutons attach to the dendritic shaft by puncta adherentia junctions (PAJs) and wrap around a multiply-branched spine, forming synaptic junctions. Here, we electron microscopically analyzed the ultrastructure of this synapse in afadin-deficient mice. Transmission electron microscopy analysis revealed that typical PAJs with prominent symmetrical plasma membrane darkening undercoated with the thick filamentous cytoskeleton were observed in the control synapse, whereas in the afadin-deficient synapse, atypical PAJs with the symmetrical plasma membrane darkening, which was much less in thickness and darkness than those of the control typical PAJs, were observed. Immunoelectron microscopy analysis revealed that nectin-1, nectin-3, and N-cadherin were localized at the control typical PAJs, whereas nectin-1 and nectin-3 were localized at the afadin-deficient atypical PAJs to extents lower than those in the control synapse and N-cadherin was localized at their nonjunctional flanking regions. These results indicate that the atypical PAJs are formed by nectin-1 and nectin-3 independently of afadin and N-cadherin and that the typical PAJs are formed by afadin and N-cadherin cooperatively with nectin-1 and nectin-3. Serial block face-scanning electron microscopy analysis revealed that the complexity of postsynaptic spines and mossy fiber boutons, the number of spine heads, the area of postsynaptic densities, and the density of synaptic vesicles docked to active zones were decreased in the afadin-deficient synapse. These results indicate that afadin plays multiple roles in the complex ultrastructural morphogenesis of hippocampal mossy fiber synapses.

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Dynamics of nascent and active zone ultrastructure as synapses enlarge during long‐term potentiation in mature hippocampus

Cited by 63 publications

References 149 publications

Structural Components of Synaptic Plasticity and Memory Consolidation

Structural Components of Synaptic Plasticity and Memory Consolidation

Dendritic Spines

Multiple roles of afadin in the ultrastructural morphogenesis of mouse hippocampal mossy fiber synapses

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