scholarly journals Stable but not rigid: Chronic in vivo STED nanoscopy reveals extensive remodeling of spines, indicating multiple drivers of plasticity

2021 ◽  
Vol 7 (24) ◽  
pp. eabf2806
Author(s):  
Heinz Steffens ◽  
Alexander C. Mott ◽  
Siyuan Li ◽  
Waja Wegner ◽  
Pavel Švehla ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Excitatory Synapses ◽  
Memory Locus ◽  
Length Width ◽  
Highly Correlated ◽  
High Degree ◽  
Distinct Features

Excitatory synapses on dendritic spines of pyramidal neurons are considered a central memory locus. To foster both continuous adaption and the storage of long-term information, spines need to be plastic and stable at the same time. Here, we advanced in vivo STED nanoscopy to superresolve distinct features of spines (head size and neck length/width) in mouse neocortex for up to 1 month. While LTP-dependent changes predict highly correlated modifications of spine geometry, we find both, uncorrelated and correlated dynamics, indicating multiple independent drivers of spine remodeling. The magnitude of this remodeling suggests substantial fluctuations in synaptic strength. Despite this high degree of volatility, all spine features exhibit persistent components that are maintained over long periods of time. Furthermore, chronic nanoscopy uncovers structural alterations in the cortex of a mouse model of neurodegeneration. Thus, at the nanoscale, stable dendritic spines exhibit a delicate balance of stability and volatility.

scholarly journals Stable but not rigid: Long-term in vivo STED nanoscopy uncovers extensive remodeling of stable spines and indicates multiple drivers of structural plasticity

2020 ◽  
Author(s):  
Heinz Steffens ◽  
Alexander C. Mott ◽  
Siyuan Li ◽  
Waja Wegner ◽  
Pavel Švehla ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Excitatory Synapses ◽  
Neck Length ◽  
Memory Locus ◽  
Highly Correlated ◽  
High Degree ◽  
Distinct Features

ABSTRACTExcitatory synapses on dendritic spines of pyramidal neurons are considered a central memory locus. To foster both continuous adaption as well as the storage of long-term information, spines need to be plastic and stable at the same time. Here we advanced in vivo STED nanoscopy to superresolve distinct features of dendritic spines (head size, neck length and width) in mouse neocortex for up to one month. While LTP-dependent changes predict highly correlated modifications of spine geometry, we find both, uncorrelated dynamics, as well as correlated changes, indicating multiple independent drivers of spine remodeling. The magnitude of this remodeling suggests substantial fluctuations in synaptic strength, and is exaggerated in a mouse model of neurodegeneration. Despite this high degree of volatility, all spine features also exhibit persistent components that are maintained over long periods of time. Thus, at the nanoscale, stable dendritic spines exhibit a delicate balance of stability and volatility.

scholarly journals Protein kinase D promotes plasticity-induced F-actin stabilization in dendritic spines and regulates memory formation

2015 ◽  
Vol 210 (5) ◽  
pp. 771-783 ◽  
Author(s):  
Norbert Bencsik ◽  
Zsófia Szíber ◽  
Hanna Liliom ◽  
Krisztián Tárnok ◽  
Sándor Borbély ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Protein Kinase ◽  
Dendritic Spines ◽  
Morphological Changes ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Protein Kinase D

Actin turnover in dendritic spines influences spine development, morphology, and plasticity, with functional consequences on learning and memory formation. In nonneuronal cells, protein kinase D (PKD) has an important role in stabilizing F-actin via multiple molecular pathways. Using in vitro models of neuronal plasticity, such as glycine-induced chemical long-term potentiation (LTP), known to evoke synaptic plasticity, or long-term depolarization block by KCl, leading to homeostatic morphological changes, we show that actin stabilization needed for the enlargement of dendritic spines is dependent on PKD activity. Consequently, impaired PKD functions attenuate activity-dependent changes in hippocampal dendritic spines, including LTP formation, cause morphological alterations in vivo, and have deleterious consequences on spatial memory formation. We thus provide compelling evidence that PKD controls synaptic plasticity and learning by regulating actin stability in dendritic spines.

scholarly journals Ciliary neuropeptidergic signaling dynamically regulates excitatory synapses in postnatal neocortical pyramidal neurons

2020 ◽  
Author(s):  
Lauren Tereshko ◽  
Ya Gao ◽  
Brian A. Cary ◽  
Gina G. Turrigiano ◽  
Piali Sengupta
Keyword(s):  
Primary Cilia ◽  
Neuronal Development ◽  
Pyramidal Neurons ◽  
Somatostatin Receptor ◽  
Cognitive Disorders ◽  
Mammalian Brain ◽  
Excitatory Synapses ◽  
Ciliary Signaling ◽  
Neocortical Pyramidal Neurons

ABSTRACTPrimary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured neocortical pyramidal neurons, and increases spontaneous firing. This increased excitability occurs without changes to passive neuronal properties or intrinsic excitability. Further, the neuropeptide receptor somatostatin receptor 3 (SSTR3) is localized nearly exclusively to pyramidal neuron cilia both in vivo and in culture, and pharmacological manipulation of SSTR3 signaling bidirectionally modulates excitatory synaptic inputs onto these neurons. Our results indicate that ciliary neuropeptidergic signaling dynamically modulates excitatory synapses, and suggest that defects in this regulation may underlie a subset of behavioral and cognitive disorders associated with ciliopathies.

scholarly journals Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling

2016 ◽  
Author(s):  
Tharkika Nagendran ◽  
Rylan S. Larsen ◽  
Rebecca L. Bigler ◽  
Shawn B. Frost ◽  
Benjamin D. Philpot ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Pyramidal Neurons ◽  
Spine Density ◽  
Axon Injury ◽  
Synaptic Remodeling ◽  
Nerve Tracts ◽  
Specific Increase ◽  
Microfluidic Chambers

AbstractInjury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability, thus influencing recovery. Due to the complexity of the CNS, a mechanistic understanding of injury-induced synaptic remodeling remains unclear. Using microfluidic chambers to separate and injure distal axons, we show that axotomy causes retrograde dendritic spine loss at directly injured pyramidal neurons followed by retrograde presynaptic hyper-excitability. These remodeling events require activity at the site of injury, axon-to-soma signaling, and transcription. Similarly, directly injured corticospinal neurons in vivo also exhibit a specific increase in spiking following axon injury. Axotomy-induced hyper-excitability of cultured neurons coincides with elimination of inhibitory inputs onto injured neurons, including those formed onto dendritic spines. Netrin-1 downregulation occurs following axon injury and exogenous netrin-1 applied after injury normalizes spine density, presynaptic excitability, and inhibitory inputs at injured neurons. Our findings show that intrinsic signaling within damaged neurons regulates synaptic remodeling and involves netrin-1 signaling.

scholarly journals Chemical LTD, but not LTP, induces transient accumulation of gelsolin in dendritic spines

2019 ◽  
Vol 400 (9) ◽  
pp. 1129-1139 ◽  
Author(s):  
Iryna Hlushchenko ◽  
Pirta Hotulainen
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Excitatory Synapses ◽  
Signal Molecule ◽  
Brain Functions ◽  
Dendritic Shaft ◽  
Term Potentiation

Abstract Synaptic plasticity underlies central brain functions, such as learning. Ca2+ signaling is involved in both strengthening and weakening of synapses, but it is still unclear how one signal molecule can induce two opposite outcomes. By identifying molecules, which can distinguish between signaling leading to weakening or strengthening, we can improve our understanding of how synaptic plasticity is regulated. Here, we tested gelsolin’s response to the induction of chemical long-term potentiation (cLTP) or long-term depression (cLTD) in cultured rat hippocampal neurons. We show that gelsolin relocates from the dendritic shaft to dendritic spines upon cLTD induction while it did not show any relocalization upon cLTP induction. Dendritic spines are small actin-rich protrusions on dendrites, where LTD/LTP-responsive excitatory synapses are located. We propose that the LTD-induced modest – but relatively long-lasting – elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin. As F-actin is enriched in dendritic spines, it is probable that increased affinity to F-actin induces the relocalization of gelsolin.

scholarly journals Activity-Induced Long-Term Potentiation of Excitatory Synapses in Developing Zebrafish Retina In Vivo

Neuron ◽  
2012 ◽  
Vol 75 (3) ◽  
pp. 479-489 ◽  
Author(s):  
Hong-ping Wei ◽  
Yuan-yuan Yao ◽  
Rong-wei Zhang ◽  
Xiao-feng Zhao ◽  
Jiu-lin Du
Keyword(s):  
Long Term Potentiation ◽  
Excitatory Synapses ◽  
Term Potentiation

scholarly journals Information encoded in volumes and areas of dendritic spines is nearly maximal across mammalian brains

2021 ◽  
Author(s):  
Jan Karbowski ◽  
Paulina Urban
Keyword(s):  
Dendritic Spines ◽  
Excitatory Synapses ◽  
Information Efficiency ◽  
Spine Length ◽  
Entropy Maximization ◽  
Surface Areas ◽  
Heavy Tailed Distributions ◽  
Mean Size ◽  
Heavy Tailed

Long-term information associated with neuronal memory resides in dendritic spines. However, spines can have a limited size due to metabolic and neuroanatomical constraints, which should effectively limit the amount of encoded information in excitatory synapses. This study investigates how much information can be stored in the sizes of dendritic spines, and whether is it optimal in any sense? It is shown here, using empirical data for several mammalian brains across different regions and physiological conditions, that dendritic spines nearly maximize entropy contained in their volumes and surface areas for a given mean size. This result is essentially independent of the type of a fitting distribution to size data, as both short- and heavy-tailed distributions yield similar nearly 100 % information efficiency in the majority of cases, although heavy-tailed distributions slightly better fit the data. On average, the highest information is contained in spine volume, and the lowest in spine length or spine head diameter. Depending on a species and brain region, a typical spine can encode between 6.1 and 10.8 bits of information in its volume, and 3.1-8.1 bits in its surface area. Our results suggest a universality of entropy maximization in spine volumes and areas, which can be a new principle of memory storing in synapses.

scholarly journals Distinct in vivo dynamics of excitatory synapses onto cortical pyramidal neurons and parvalbumin-positive interneurons

Cell Reports ◽  
2021 ◽  
Vol 37 (6) ◽  
pp. 109972
Author(s):  
Joshua B. Melander ◽  
Aran Nayebi ◽  
Bart C. Jongbloets ◽  
Dale A. Fortin ◽  
Maozhen Qin ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Excitatory Synapses ◽  
Cortical Pyramidal Neurons

scholarly journals N-terminal alternative splicing of GluN1 regulates the maturation of excitatory synapses and seizure susceptibility

2019 ◽  
Vol 116 (42) ◽  
pp. 21207-21212 ◽  
Author(s):  
Hong Liu ◽  
Hao Wang ◽  
Matthew Peterson ◽  
Wen Zhang ◽  
Guoqiang Hou ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Developmental Change ◽  
Brain Regions ◽  
Excitatory Synapses ◽  
Seizure Susceptibility ◽  
Adult Mice ◽  
Splicing Variants ◽  
Functional Analyses ◽  
Developmental Remodeling

The majority of NMDA receptors (NMDARs) in the brain are composed of 2 GluN1 and 2 GluN2 subunits. The inclusion or exclusion of 1 N-terminal and 2 C-terminal domains of GluN1 results in 8 splicing variants that exhibit distinct temporal and spatial patterns of expression and functional properties. However, previous functional analyses of Grin1 variants have been done using heterologous expression and the in vivo function of Grin1 splicing is unknown. Here we show that N-terminal splicing of GluN1 has important functions in the maturation of excitatory synapses. The inclusion of exon 5 of Grin1 is up-regulated in several brain regions such as the thalamus and neocortex. We find that deletion of Grin1 exon 5 disrupts the developmental remodeling of NMDARs in thalamic neurons and the effect is distinct from that of Grin2a (GluN2A) deletion. Deletion of Grin2a or exon 5 of Grin1 alone partially attenuates the shortening of NMDAR-mediated excitatory postsynaptic currents (NMDAR-EPSCs) during early life, whereas deletion of both Grin2a and exon 5 of Grin1 completely abolishes the developmental change in NMDAR-EPSC decay time. Deletion of exon 5 of Grin1 leads to an overproduction of excitatory synapses in layer 5 pyramidal neurons in the cortex and increases seizure susceptibility in adult mice. Our findings demonstrate that N-terminal splicing of GluN1 has important functions in synaptic maturation and neuronal network excitability.

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