Hippocampal ripples down-regulate synapses

Science ◽  
2018 ◽  
Vol 359 (6383) ◽  
pp. 1524-1527 ◽  
Author(s):  
Hiroaki Norimoto ◽  
Kenichi Makino ◽  
Mengxuan Gao ◽  
Yu Shikano ◽  
Kazuki Okamoto ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Activity ◽  
Slow Wave ◽  
Down Regulation ◽  
Sharp Wave ◽  
Specific Effects ◽  
Aspartate Receptor ◽  
Specific Input ◽  
Wave States

The specific effects of sleep on synaptic plasticity remain unclear. We report that mouse hippocampal sharp-wave ripple oscillations serve as intrinsic events that trigger long-lasting synaptic depression. Silencing of sharp-wave ripples during slow-wave states prevented the spontaneous down-regulation of net synaptic weights and impaired the learning of new memories. The synaptic down-regulation was dependent on the N-methyl-d-aspartate receptor and selective for a specific input pathway. Thus, our findings are consistent with the role of slow-wave states in refining memory engrams by reducing recent memory-irrelevant neuronal activity and suggest a previously unrecognized function for sharp-wave ripples.

scholarly journals Role of neuronal activity and metaplastic state in homeostatic synaptic plasticity

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S402-S403
Author(s):  
Bryce Grier ◽  
Varun Chokshi ◽  
Andrew Dykman ◽  
Crystal Lantz ◽  
Ernst Niebur ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Activity ◽  
Homeostatic Synaptic Plasticity

scholarly journals Neuronal megalin mediates synaptic plasticity—a novel mechanism underlying intellectual disabilities in megalin gene pathologies

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
João R Gomes ◽  
Andrea Lobo ◽  
Renata Nogueira ◽  
Ana F Terceiro ◽  
Susete Costelha ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Intellectual Disabilities ◽  
Learning And Memory ◽  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Genetic Disorder ◽  
Cell Surface Receptor ◽  
Neuronal Cultures

Abstract Donnai-Barrow syndrome, a genetic disorder associated to LRP2 (low-density lipoprotein receptor 2/megalin) mutations, is characterized by unexplained neurological symptoms and intellectual deficits. Megalin is a multifunctional endocytic clearance cell-surface receptor, mostly described in epithelial cells. This receptor is also expressed in the CNS, mainly in neurons, being involved in neurite outgrowth and neuroprotective mechanisms. Yet, the mechanisms involved in the regulation of megalin in the CNS are poorly understood. Using transthyretin knockout mice, a megalin ligand, we found that transthyretin positively regulates neuronal megalin levels in different CNS areas, particularly in the hippocampus. Transthyretin is even able to rescue megalin downregulation in transthyretin knockout hippocampal neuronal cultures, in a positive feedback mechanism via megalin. Importantly, transthyretin activates a regulated intracellular proteolysis mechanism of neuronal megalin, producing an intracellular domain, which is translocated to the nucleus, unveiling megalin C-terminal as a potential transcription factor, able to regulate gene expression. We unveil that neuronal megalin reduction affects physiological neuronal activity, leading to decreased neurite number, length and branching, and increasing neuronal susceptibility to a toxic insult. Finally, we unravel a new unexpected role of megalin in synaptic plasticity, by promoting the formation and maturation of dendritic spines, and contributing for the establishment of active synapses, both in in vitro and in vivo hippocampal neurons. Moreover, these structural and synaptic roles of megalin impact on learning and memory mechanisms, since megalin heterozygous mice show hippocampal-related memory and learning deficits in several behaviour tests. Altogether, we unveil a complete novel role of megalin in the physiological neuronal activity, mainly in synaptic plasticity with impact in learning and memory. Importantly, we contribute to disclose the molecular mechanisms underlying the cognitive and intellectual disabilities related to megalin gene pathologies.

scholarly journals Coupling between slow waves and sharp-wave ripples engages distributed neural activity during sleep in humans

2021 ◽  
Vol 118 (21) ◽  
pp. e2012075118
Author(s):  
Ivan Skelin ◽  
Haoxin Zhang ◽  
Jie Zheng ◽  
Shiting Ma ◽  
Bryce A. Mander ◽  
...  
Keyword(s):  
Slow Wave ◽  
Memory Consolidation ◽  
Temporal Cortex ◽  
Neuronal Ensembles ◽  
Neuronal Populations ◽  
Sharp Wave ◽  
Regional Coordination ◽  
Electrophysiological Recordings ◽  
High Frequency Activity

Hippocampal-dependent memory consolidation during sleep is hypothesized to depend on the synchronization of distributed neuronal ensembles, organized by the hippocampal sharp-wave ripples (SWRs, 80 to 150 Hz), subcortical/cortical slow-wave activity (SWA, 0.5 to 4 Hz), and sleep spindles (SP, 7 to 15 Hz). However, the precise role of these interactions in synchronizing subcortical/cortical neuronal activity is unclear. Here, we leverage intracranial electrophysiological recordings from the human hippocampus, amygdala, and temporal and frontal cortices to examine activity modulation and cross-regional coordination during SWRs. Hippocampal SWRs are associated with widespread modulation of high-frequency activity (HFA, 70 to 200 Hz), a measure of local neuronal activation. This peri-SWR HFA modulation is predicted by the coupling between hippocampal SWRs and local subcortical/cortical SWA or SP. Finally, local cortical SWA phase offsets and SWR amplitudes predicted functional connectivity between the frontal and temporal cortex during individual SWRs. These findings suggest a selection mechanism wherein hippocampal SWR and cortical slow-wave synchronization governs the transient engagement of distributed neuronal populations supporting hippocampal-dependent memory consolidation.

scholarly journals Cornichon Homolog-3 (CNIH3) Modulates Spatial Memory in Female Mice

2019 ◽  
Author(s):  
Hannah E. Frye ◽  
Sidney B. Williams ◽  
Christopher R. Trousdale ◽  
Elliot C. Nelson ◽  
Joseph D. Dougherty ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Spatial Memory ◽  
Dorsal Hippocampus ◽  
Postsynaptic Membrane ◽  
Spatial Learning And Memory ◽  
Female Mice ◽  
Specific Effects ◽  
Hippocampal Synaptic Plasticity ◽  
Auxiliary Protein

ABSTRACTCornichon homolog-3 (CNIH3) is an AMPA receptor (AMPAR) auxiliary protein that traffics AMPARs to the postsynaptic membrane and potentiates AMPAR signaling. AMPARs are key components of hippocampal synaptic plasticity and memory formation, however the role of CNIH3 in memory has yet to be elucidated. To study the role of CNIH3 on mouse behavior, we bred and characterized a line of Cnih3-/- mice from C57BL/6 Cnih3tm1a(KOMP)Wtsi mice obtained from the Knockout Mouse Project (KOMP). In agreement with previous studies of CNIH3 in the brain, we observed concentrated expression of Cnih3 in the dorsal hippocampus, a region associated with spatial learning and memory. Therefore, we tested Cnih3+/+, Cnih3+/-, and Cnih3-/- mice in the Barnes maze paradigm to measure spatial memory. We observed no change in spatial memory in male Cnih3+/- and Cnih3-/- mice compared to male Cnih3+/+ controls, however, Cnih3-/- female mice made significantly more primary errors, had a higher primary latency, and took less efficient routes to the target in the maze compared to Cnih3+/+ female mice. Next, to investigate an enhancement of spatial memory by Cnih3 overexpression, specifically in the dorsal hippocampus, we developed an AAV5 viral construct to express wild-type Cnih3 in excitatory neurons. Female mice overexpressing Cnih3 made significantly fewer errors, had a lower primary latency to the target, and took more efficient routes to the maze target compared to YFP expressing control females. No change in spatial memory was observed in male Cnih3 overexpression mice. This study, the first to identify sex-specific effects of the AMPAR auxiliary protein CNIH3 on spatial memory, provides the groundwork for future studies investigating the role of CNIH3 on sexually dimorphic AMPAR-dependent behavior and hippocampal synaptic plasticity.

scholarly journals Staufen1 Regulation of Protein Synthesis-Dependent Long-Term Potentiation and Synaptic Function in Hippocampal Pyramidal Cells

2008 ◽  
Vol 28 (9) ◽  
pp. 2896-2907 ◽  
Author(s):  
Geneviève Lebeau ◽  
Marjolaine Maher-Laporte ◽  
Lisa Topolnik ◽  
Charles E. Laurent ◽  
Wayne Sossin ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Translational Control ◽  
Rna Binding ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Down Regulation ◽  
Spine Shape ◽  
Term Potentiation

ABSTRACT Staufen1 (Stau1) is an RNA-binding protein involved in transport, localization, decay, and translational control of mRNA. In neurons, it is present in cell bodies and also in RNA granules which are transported along dendrites. Dendritic mRNA localization might be involved in long-term synaptic plasticity and memory. To determine the role of Stau1 in synaptic function, we examined the effects of Stau1 down-regulation in hippocampal slice cultures using small interfering RNA (siRNA). Biolistic transfection of Stau1 siRNA resulted in selective down-regulation of Stau1 in slice cultures. Consistent with a role of Stau1 in transporting mRNAs required for synaptic plasticity, Stau1 down-regulation impaired the late form of chemically induced long-term potentiation (L-LTP) without affecting early-LTP, mGluR1/5-mediated long-term depression, or basal evoked synaptic transmission. Stau1 down-regulation decreased the amplitude and frequency of miniature excitatory postsynaptic currents, suggesting a role in maintaining efficacy at hippocampal synapses. At the cellular level, Stau1 down-regulation shifted spine shape from regular to elongated spines, without changes in spine density. The change in spine shape could be rescued by an RNA interference-resistant Stau1 isoform. Therefore, Stau1 is important for processing and/or transporting in dendrites mRNAs that are critical in regulation of synaptic strength and maintenance of functional connectivity changes underlying hippocampus-dependent learning and memory.

scholarly journals Down-regulation of habenular calcium-dependent secretion activator 2 induces despair-like behavior

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hyeijung Yoo ◽  
Soo Hyun Yang ◽  
Jin Yong Kim ◽  
Esther Yang ◽  
Hyung Sun Park ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Learned Helplessness ◽  
Down Regulation ◽  
Depressive Behavior ◽  
Interpeduncular Nucleus ◽  
Calcium Dependent ◽  
Neuropeptide Secretion ◽  
Medial Habenula ◽  
Model Mouse

AbstractCalcium-dependent secretion activator 2 (CAPS2) regulates the trafficking and exocytosis of neuropeptide-containing dense-core vesicles (DCVs). CAPS2 is prominently expressed in the medial habenula (MHb), which is related to depressive behavior; however, how MHb neurons cause depressive symptoms and the role of CAPS2 remains unclear. We hypothesized that dysfunction of MHb CAPS neurons might cause defects in neuropeptide secretion and the activity of monoaminergic centers, resulting in depressive-like behaviors. In this study, we examined (1) CAPS2 expression in the habenula of depression animal models and major depressive disorder patients and (2) the effects of down-regulation of MHb CAPS2 on the animal behaviors, synaptic transmission in the interpeduncular nucleus (IPN), and neuronal activity of monoamine centers. Habenular CAPS2 expression was decreased in the rat chronic restraint stress model, mouse learned helplessness model, and showed tendency to decrease in depression patients who died by suicide. Knockdown of CAPS2 in the mouse habenula evoked despair-like behavior and a reduction of the release of DCVs in the IPN. Neuronal activity of IPN and monoaminergic centers was also reduced. These results implicate MHb CAPS2 as playing a pivotal role in depressive behavior through the regulation of neuropeptide secretion of the MHb-IPN pathway and the activity of monoaminergic centers.

Sign in / Sign up

Export Citation Format

Share Document