scholarly journals Neuronal activity remodels the F-actin based submembrane lattice in dendrites but not axons of hippocampal neurons

2020 ◽  
Author(s):  
Flavie Lavoie-Cardinal ◽  
Anthony Bilodeau ◽  
Mado Lemieux ◽  
Marc-André Gardner ◽  
Theresa Wiesner ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Neuronal Activity ◽  
Protein Trafficking ◽  
Hippocampal Neurons ◽  
Actin Remodeling ◽  
Fluorescence Nanoscopy ◽  
Segmentation Approach ◽  
Weakly Supervised ◽  
Activity Dependent ◽  
Actin Rings

AbstractThe nanoscale organization of the F-actin cytoskeleton in neurons comprises membrane-associated periodical rings, bundles, and longitudinal fibers. The F-actin rings have been observed predominantly in axons but only sporadically in dendrites, where fluorescence nanoscopy reveals various patterns of F-actin arranged in mixed patches. These complex dendritic F-actin patterns pose a challenge for investigating quantitatively their regulatory mechanisms. We developed here a weakly supervised deep learning segmentation approach of fluorescence nanoscopy images of F-actin in cultured hippocampal neurons. This approach enabled the quantitative assessment of F-actin remodeling, revealing the disappearance of the rings during neuronal activity in dendrites, but not in axons. The dendritic F-actin cytoskeleton of activated neurons remodeled into longitudinal fibers. We show that this activity-dependent remodeling involves Ca2+ and NMDA-dependent mechanisms. This highly dynamic restructuring of dendritic F-actin based submembrane lattice into longitudinal fibers may serve to support activity-dependent membrane remodeling, protein trafficking and neuronal plasticity.

scholarly journals Systematic identification of 3′-UTR regulatory elements in activity-dependent mRNA stability in hippocampal neurons

2014 ◽  
Vol 369 (1652) ◽  
pp. 20130509 ◽  
Author(s):  
Jonathan E. Cohen ◽  
Philip R. Lee ◽  
R. Douglas Fields
Keyword(s):  
Neuronal Activity ◽  
Mrna Stability ◽  
Hippocampal Neurons ◽  
Transcriptional Control ◽  
Regulatory Elements ◽  
Memory Storage ◽  
Long Term Memory ◽  
Synaptic Connections ◽  
Activity Dependent

Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long-term memory storage. Activity-dependent, post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity in rat hippocampal neurons. In this study, we demonstrate rapid, post-transcriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3′-UTRs of destabilized transcripts, identifies enrichment in sequence motifs corresponding to microRNA (miRNA)-binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further find that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory.

scholarly journals Ps in the (Channel) Pod Are Not Alike …

2007 ◽  
Vol 7 (5) ◽  
pp. 136-137
Author(s):  
Yoav Noam ◽  
Tallie Z. Baram
Keyword(s):  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Phosphorylation Sites ◽  
Voltage Dependent ◽  
Activity Dependent ◽  
Stimulation Of ◽  
Cultured Hippocampal Neurons

Bidirectional Activity-Dependent Regulation of Neuronal Ion Channel Phosphorylation. Misonou H, Menegola M, Mohapatra DP, Guy LK, Park KS, Trimmer JS. J Neurosci 2006;26(52):13505–13514. Activity-dependent dephosphorylation of neuronal Kv2.1 channels yields hyperpolarizing shifts in their voltage-dependent activation and homoeostatic suppression of neuronal excitability. We recently identified 16 phosphorylation sites that modulate Kv2.1 function. Here, we show that in mammalian neurons, compared with other regulated sites, such as serine (S)563, phosphorylation at S603 is supersensitive to calcineurin-mediated dephosphorylation in response to kainate-induced seizures in vivo, and brief glutamate stimulation of cultured hippocampal neurons. In vitro calcineurin digestion shows that supersensitivity of S603 dephosphorylation is an inherent property of Kv2.1. Conversely, suppression of neuronal activity by anesthetic in vivo causes hyperphosphorylation at S603 but not S563. Distinct regulation of individual phosphorylation sites allows for graded and bidirectional homeostatic regulation of Kv2.1 function. S603 phosphorylation represents a sensitive bidirectional biosensor of neuronal activity.

scholarly journals Regulation of TrkB receptor tyrosine kinase and its internalization by neuronal activity and Ca2+ influx

2003 ◽  
Vol 163 (2) ◽  
pp. 385-395 ◽  
Author(s):  
Jing Du ◽  
Linyin Feng ◽  
Eugene Zaitsev ◽  
Hyun-Soo Je ◽  
Xu-wen Liu ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Neuronal Activity ◽  
Cell Biology ◽  
Hippocampal Neurons ◽  
Electric Stimulation ◽  
Kinase Activity ◽  
Critical Role ◽  
Tyrosine Kinase Activity ◽  
Internalization Process ◽  
Activity Dependent

Internalization of the neurotrophin–Trk receptor complex is critical for many aspects of neurotrophin functions. The mechanisms governing the internalization process are unknown. Here, we report that neuronal activity facilitates the internalization of the receptor for brain-derived neurotrophic factor, TrkB, by potentiating its tyrosine kinase activity. Using three independent approaches, we show that electric stimulation of hippocampal neurons markedly enhances TrkB internalization. Electric stimulation also potentiates TrkB tyrosine kinase activity. The activity-dependent enhancement of TrkB internalization and its tyrosine kinase requires Ca2+ influx through N-methyl-d-aspartate receptors and Ca2+ channels. Inhibition of internalization had no effect on TrkB kinase, but inhibition of TrkB kinase prevents the modulation of TrkB internalization, suggesting a critical role of the tyrosine kinase in the activity-dependent receptor endocytosis. These results demonstrate an activity- and Ca2+-dependent modulation of TrkB tyrosine kinase and its internalization, and they provide new insights into the cell biology of tyrosine kinase receptors.

scholarly journals Activity-dependent BDNF release via endocytic pathways is regulated by synaptotagmin-6 and complexin

2015 ◽  
Vol 112 (32) ◽  
pp. E4475-E4484 ◽  
Author(s):  
Yu-Hui Wong ◽  
Chia-Ming Lee ◽  
Wenjun Xie ◽  
Bianxiao Cui ◽  
Mu-ming Poo
Keyword(s):  
Quantum Dots ◽  
Glutamate Receptors ◽  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Synaptic Modulation ◽  
Activity Dependent ◽  
Endocytic Pathways ◽  
Cultured Hippocampal Neurons

Brain-derived neurotrophic factor (BDNF) is known to modulate synapse development and plasticity, but the source of synaptic BDNF and molecular mechanisms regulating BDNF release remain unclear. Using exogenous BDNF tagged with quantum dots (BDNF-QDs), we found that endocytosed BDNF-QDs were preferentially localized to postsynaptic sites in the dendrite of cultured hippocampal neurons. Repetitive neuronal spiking induced the release of BDNF-QDs at these sites, and this process required activation of glutamate receptors. Down-regulating complexin 1/2 (Cpx1/2) expression eliminated activity-induced BDNF-QD secretion, although the overall activity-independent secretion was elevated. Among eight synaptotagmin (Syt) isoforms examined, down-regulation of only Syt6 impaired activity-induced BDNF-QD secretion. In contrast, activity-induced release of endogenously synthesized BDNF did not depend on Syt6. Thus, neuronal activity could trigger the release of endosomal BDNF from postsynaptic dendrites in a Cpx- and Syt6-dependent manner, and endosomes containing BDNF may serve as a source of BDNF for activity-dependent synaptic modulation.

scholarly journals Activity- and Ca2+-Dependent Modulation of Surface Expression of Brain-Derived Neurotrophic Factor Receptors in Hippocampal Neurons

2000 ◽  
Vol 150 (6) ◽  
pp. 1423-1434 ◽  
Author(s):  
Jing Du ◽  
Linyin Feng ◽  
Feng Yang ◽  
Bai Lu
Keyword(s):  
Neuronal Activity ◽  
Neurotrophic Factor ◽  
High Frequency ◽  
Hippocampal Neurons ◽  
Electric Stimulation ◽  
Low Frequency ◽  
Brain Derived Neurotrophic Factor ◽  
Dependent Manner ◽  
Tetanic Stimulation ◽  
Activity Dependent

Brain-derived neurotrophic factor (BDNF) has been shown to regulate neuronal survival and synaptic plasticity in the central nervous system (CNS) in an activity-dependent manner, but the underlying mechanisms remain unclear. Here we report that the number of BDNF receptor TrkB on the surface of hippocampal neurons can be enhanced by high frequency neuronal activity and synaptic transmission, and this effect is mediated by Ca2+ influx. Using membrane protein biotinylation as well as receptor binding assays, we show that field electric stimulation increased the number of TrkB on the surface of cultured hippocampal neurons. Immunofluorescence staining suggests that the electric stimulation facilitated the movement of TrkB from intracellular pool to the cell surface, particularly on neuronal processes. The number of surface TrkB was regulated only by high frequency tetanic stimulation, but not by low frequency stimulation. The activity dependent modulation appears to require Ca2+ influx, since treatment of the neurons with blockers of voltage-gated Ca2+ channels or NMDA receptors, or removal of extracellular Ca2+, severely attenuated the effect of electric stimulation. Moreover, inhibition of Ca2+/calmodulin-dependent kinase II (CaMKII) significantly reduced the effectiveness of the tetanic stimulation. These findings may help us to understand the role of neuronal activity in neurotrophin function and the mechanism for receptor tyrosine kinase signaling.

scholarly journals Neuronal Activity-Dependent Accumulation of Arc in Astrocytes

2020 ◽  
Author(s):  
Yuheng Jiang ◽  
Antonius M.J. VanDongen
Keyword(s):  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Early Gene ◽  
Dependent Manner ◽  
Pharmacological Agents ◽  
Network Activation ◽  
Term Potentiation ◽  
Activity Dependent

AbstractThe immediate-early gene Arc is a master regulator of synaptic plasticity and plays a critical role in memory consolidation. However, there has not been a comprehensive analysis of the itinerary of Arc protein, linking its function at different subcellular locations with corresponding time points after neuronal network activation. When cultured hippocampal neurons are treated with a combination of pharmacological agents to induce long term potentiation, they express high levels of Arc, allowing to study its spatiotemporal distribution. Our experiments show that neuronal activity-induced Arc expression was not restricted to neurons, but that its spatiotemporal dynamics involved a shift to astrocytes at a later timepoint. Specifically, astrocytic Arc is not due to endogenous transcription, but is dependent on the production of neuronal Arc and accumulates potentially via the recently reported intercellular transfer mechanism through Arc capsids. In conclusion, we found that Arc accumulates within astrocytes in a neuronal activity-dependent manner, which is independent of endogenous astrocytic Arc transcription, therefore highlighting the need to study the purpose of this pool of Arc, especially in learning and memory.

scholarly journals Activity-dependent nucleation of dynamic microtubules at presynaptic boutons is required for neurotransmission

2019 ◽  
Author(s):  
Xiaoyi Qu ◽  
Atul Kumar ◽  
Heike Blockus ◽  
Clarissa Waites ◽  
Francesca Bartolini
Keyword(s):  
Synaptic Vesicle ◽  
Neuronal Activity ◽  
Neurotransmitter Release ◽  
Hippocampal Neurons ◽  
De Novo ◽  
List Type ◽  
Neuronal Function ◽  
Presynaptic Boutons ◽  
Rate Limiting ◽  
Activity Dependent

SUMMARYControl of microtubule (MT) dynamics is critical for neuronal function. Whether MT nucleation is regulated at presynaptic boutons and influences overall presynaptic activity remains unknown. By visualizing MT dynamics at individual excitatory en passant boutons in axons of hippocampal neurons we found that MTs preferentially grow from presynaptic boutons as a result of γ-tubulin and augmin-dependent nucleation. MT nucleation at boutons is promoted by neuronal activity, functionally coupled to synaptic vesicle (SV) transport, and required for neurotransmission. Hence, en passant boutons act as hotspots for activity-dependent MT nucleation, which is required for neurotransmission by providing the tracks for a rate-limiting supply of SVs to sites of neurotransmitter release.HighlightsExcitatory boutons are hotspots for neuronal activity-induced γ-tubulin dependent MT nucleationThe augmin complex is required for the correct polarity of presynaptic de novo nucleated MTsPresynaptic MT nucleation promotes SV motility and exocytosis at sites of releaseIn BriefOur results demonstrate that excitatory en passant boutons are hotspots for neuronal activity-induced γ-tubulin- and augmin-dependent oriented MT nucleation, and that the resulting presynaptic de novo nucleated MTs promote inter-bouton SV motility which is rate-limiting for neurotransmitter release.

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