Erasing Synapses in Sleep: Is It Time to Be SHY?

Converging lines of evidence strongly support a role for sleep in brain plasticity. An elegant idea that may explain how sleep accomplishes this role is the “synaptic homeostasis hypothesis (SHY).” According to SHY, sleep promotes net synaptic weakening which offsets net synaptic strengthening that occurs during wakefulness. SHY is intuitively appealing because it relates the homeostatic regulation of sleep to an important function (synaptic plasticity). SHY has also received important experimental support from recent studies inDrosophila melanogaster. There remain, however, a number of unanswered questions about SHY. What is the cellular mechanism governing SHY? How does it fit with what we know about plasticity mechanisms in the brain? In this review, I discuss the evidence and theory of SHY in the context of what is known about Hebbian and non-Hebbian synaptic plasticity. I conclude that while SHY remains an elegant idea, the underlying mechanisms are mysterious and its functional significance unknown.

Download Full-text

Modulation of Synaptic Plasticity by Vibratory Training in Young and Old Mice

Brain Sciences ◽

10.3390/brainsci11010082 ◽

2021 ◽

Vol 11 (1) ◽

pp. 82

Author(s):

Ida Cariati ◽

Roberto Bonanni ◽

Gabriele Pallone ◽

Giuseppe Annino ◽

Virginia Tancredi ◽

...

Keyword(s):

Synaptic Plasticity ◽

Vibration Frequency ◽

Hippocampal Slices ◽

The Body ◽

Whole Body ◽

Negative Effects ◽

Functional Changes ◽

Underlying Mechanisms ◽

The Brain

In the past 40 years, scientific research has shown how Whole Body Vibration concept represents a strong stimulus for the whole organism. Low (<30 Hz), medium (30–80 Hz), and high (>80 Hz) frequency vibrations can have both positive and negative effects, depending on the oscillation type and duration of exposure to which the body is subjected. However, very little is known about the effects of vibratory training on the brain. In this regard, we verified whether three vibratory training protocols, differing in terms of vibration frequency and exposure time to vibration, could modulate synaptic plasticity in an experimental mouse model, by extracellular recordings in vitro in hippocampal slices of mice of 4 and 24 months old. Our results showed that vibratory training can modulate synaptic plasticity differently, depending on the protocol used, and that the best effects are related to the training protocol characterized by a low vibration frequency and a longer recovery time. Future studies will aim to understand the brain responses to various types of vibratory training and to explore the underlying mechanisms, also evaluating the presence of any structural and functional changes due to vibratory training.

Download Full-text

Why I Am Not SHY: A Reply to Tononi and Cirelli

Neural Plasticity ◽

10.1155/2013/394946 ◽

2013 ◽

Vol 2013 ◽

pp. 1-3 ◽

Cited By ~ 24

Author(s):

Marcos Gabriel Frank

Keyword(s):

Structural and Functional Modulation of Perineuronal Nets: In Search of Important Players with Highlight on Tenascins

Cells ◽

10.3390/cells10061345 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1345

Author(s):

Ana Jakovljević ◽

Milena Tucić ◽

Michaela Blažiková ◽

Andrej Korenić ◽

Yannis Missirlis ◽

...

Keyword(s):

Synaptic Plasticity ◽

Brain Plasticity ◽

Super Resolution ◽

Perineuronal Nets ◽

Optimal Conditions ◽

Neuronal Function ◽

Specialized Form ◽

Functional Modulation ◽

Super Resolution Microscopy ◽

The Brain

The extracellular matrix (ECM) of the brain plays a crucial role in providing optimal conditions for neuronal function. Interactions between neurons and a specialized form of ECM, perineuronal nets (PNN), are considered a key mechanism for the regulation of brain plasticity. Such an assembly of interconnected structural and regulatory molecules has a prominent role in the control of synaptic plasticity. In this review, we discuss novel ways of studying the interplay between PNN and its regulatory components, particularly tenascins, in the processes of synaptic plasticity, mechanotransduction, and neurogenesis. Since enhanced neuronal activity promotes PNN degradation, it is possible to study PNN remodeling as a dynamical change in the expression and organization of its constituents that is reflected in its ultrastructure. The discovery of these subtle modifications is enabled by the development of super-resolution microscopy and advanced methods of image analysis.

Download Full-text

Is Sleep Essential for Neural Plasticity in Humans, and How Does It Affect Motor and Cognitive Recovery?

Neural Plasticity ◽

10.1155/2013/103949 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 26

Author(s):

Maurizio Gorgoni ◽

Aurora D'Atri ◽

Giulia Lauri ◽

Paolo Maria Rossini ◽

Fabio Ferlazzo ◽

...

Keyword(s):

Synaptic Plasticity ◽

Sleep Quality ◽

Beneficial Effect ◽

Neural Plasticity ◽

Point Of View ◽

Specific Nature ◽

Synaptic Homeostasis ◽

Recovery Processes ◽

Cortical Topography ◽

Underlying Mechanisms

There is a general consensus that sleep is strictly linked to memory, learning, and, in general, to the mechanisms of neural plasticity, and that this link may directly affect recovery processes. In fact, a coherent pattern of empirical findings points to beneficial effect of sleep on learning and plastic processes, and changes in synaptic plasticity during wakefulness induce coherent modifications in EEG slow wave cortical topography during subsequent sleep. However, the specific nature of the relation between sleep and synaptic plasticity is not clear yet. We reported findings in line with two models conflicting with respect to the underlying mechanisms, that is, the “synaptic homeostasis hypothesis” and the “consolidation” hypothesis, and some recent results that may reconcile them. Independently from the specific mechanisms involved, sleep loss is associated with detrimental effects on plastic processes at a molecular and electrophysiological level. Finally, we reviewed growing evidence supporting the notion that plasticity-dependent recovery could be improved managing sleep quality, while monitoring EEG during sleep may help to explain how specific rehabilitative paradigms work. We conclude that a better understanding of the sleep-plasticity link could be crucial from a rehabilitative point of view.

Download Full-text

Endocannabinoid Signaling and Synaptic Plasticity in the Brain

Critical Reviews in Neurobiology ◽

10.1615/critrevneurobiol.v18.i1-2.120 ◽

2006 ◽

Vol 18 (1-2) ◽

pp. 113-124 ◽

Cited By ~ 17

Author(s):

Ping Jun Zhu

Keyword(s):

Synaptic Plasticity ◽

The Brain

Download Full-text

Minocycline inhibits mTOR signaling activation and alleviates behavioral deficits in the Wistar rats with acute ischemia stroke

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319999200831153748 ◽

2020 ◽

Vol 19 ◽

Author(s):

Shengyuan Wang ◽

Chuanling Wang ◽

Lihua Wang ◽

Zhiyou Cai

Keyword(s):

Cerebral Ischemia ◽

Ischemia Reperfusion ◽

Mammalian Target Of Rapamycin ◽

Mtor Signaling ◽

Acute Ischemia ◽

Intragastric Administration ◽

Underlying Mechanisms ◽

Signaling Activation ◽

The Brain ◽

Minocycline Therapy

Background: Mammalian target of rapamycin (mTOR) has been evidenced as a multimodal therapy in the path-ophysiological process of acute ischemic stroke (AIS). However, the pathway that minocycline targets mTOR signaling is not fully defined in the AIS pathogenesis. This study is to aim at the effects of minocycline on the mTOR signaling in the AIS process and further discover the underlying mechanisms of minocycline involved in the following change of mTOR signaling-autophagy. Methods: Cerebral ischemia/reperfusion (CIR) rat animal models were established with the transient suture occlusion into middle cerebral artery. Minocycline (50mg/kg) was given by intragastric administration. The Morris water maze was used to test the cognitive function of animals. Immunohistochemistry and immunofluorescence were introduced for testing the lev-els of synaptophysin and PSD-95. Western blot was conducted for investigating the levels of mTOR, p-mTOR (Ser2448), p70S6, p-p70S6 (Thr389), eEF2k, p-eEF2k (Ser366), p-eIF4B (Ser406), LC3, p62, synaptophysin and PSD-95. Results: Minocycline prevents cognitive decline of the MCAO stroke rats. Minocycline limits the expression of p-mTOR (Ser2448) and the downstream targets of mTOR [p70S6, p-p70S6 (Thr389), eEF2k, p-eEF2k (Ser366) and p-eIF4B (Ser406)] (P<0.01), while minocycline has no influence on mTOR. LC3-II abundance and the LC3-II/I ratio were upregu-lated in the hippocampus of the MCAO stroke rats by the minocycline therapy (P<0.01). p62 was downregulated in the hippocampus from the MCAO stroke rats administrated with minocycline therapy(P<0.01). The levels of SYP and PSD-95 were up-regulated in the brain of the MCAO stroke rats administrated with minocycline therapy. Conclusion: Minocycline prevents cognitive deficits via inhibiting mTOR signaling and enhancing autophagy process, and promoting the expression of pre-and postsynaptic proteins (synaptophysin and PSD-95) in the brain of the MCAO stroke rats. The potential neuroprotective role of minocycline in the process of cerebral ischemia may be related to mitigating is-chemia-induced synapse injury via inhibiting activation of mTOR signaling.

Download Full-text

Correction: The Nutrient-Responsive Hormone CCHamide-2 Controls Growth by Regulating Insulin-like Peptides in the Brain of Drosophila melanogaster

PLoS Genetics ◽

10.1371/journal.pgen.1005481 ◽

2015 ◽

Vol 11 (9) ◽

pp. e1005481 ◽

Cited By ~ 4

Author(s):

Hiroko Sano ◽

Akira Nakamura ◽

Michael J. Texada ◽

James W. Truman ◽

Hiroshi Ishimoto ◽

...

Keyword(s):

Drosophila Melanogaster ◽

The Brain

Download Full-text

A new method to predict anomaly in brain network based on graph deep learning

Reviews in the Neurosciences ◽

10.1515/revneuro-2019-0108 ◽

2020 ◽

Vol 31 (6) ◽

pp. 681-689

Author(s):

Jalal Mirakhorli ◽

Hamidreza Amindavar ◽

Mojgan Mirakhorli

Keyword(s):

Deep Learning ◽

Large Scale ◽

Brain Plasticity ◽

Brain Network ◽

High Order ◽

Brain Diseases ◽

Simultaneous Occurrence ◽

Generative Adversarial Network ◽

The Brain ◽

Brain Connections

AbstractFunctional magnetic resonance imaging a neuroimaging technique which is used in brain disorders and dysfunction studies, has been improved in recent years by mapping the topology of the brain connections, named connectopic mapping. Based on the fact that healthy and unhealthy brain regions and functions differ slightly, studying the complex topology of the functional and structural networks in the human brain is too complicated considering the growth of evaluation measures. One of the applications of irregular graph deep learning is to analyze the human cognitive functions related to the gene expression and related distributed spatial patterns. Since a variety of brain solutions can be dynamically held in the neuronal networks of the brain with different activity patterns and functional connectivity, both node-centric and graph-centric tasks are involved in this application. In this study, we used an individual generative model and high order graph analysis for the region of interest recognition areas of the brain with abnormal connection during performing certain tasks and resting-state or decompose irregular observations. Accordingly, a high order framework of Variational Graph Autoencoder with a Gaussian distributer was proposed in the paper to analyze the functional data in brain imaging studies in which Generative Adversarial Network is employed for optimizing the latent space in the process of learning strong non-rigid graphs among large scale data. Furthermore, the possible modes of correlations were distinguished in abnormal brain connections. Our goal was to find the degree of correlation between the affected regions and their simultaneous occurrence over time. We can take advantage of this to diagnose brain diseases or show the ability of the nervous system to modify brain topology at all angles and brain plasticity according to input stimuli. In this study, we particularly focused on Alzheimer’s disease.

Download Full-text

Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1

Scientific Reports ◽

10.1038/s41598-021-94849-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Patricia Soriano Roque ◽

Mehdi Hooshmandi ◽

Laura Neagu-Lund ◽

Shelly Yin ◽

Noosha Yousefpour ◽

...

Keyword(s):

Cognitive Impairment ◽

Synaptic Plasticity ◽

General Anesthesia ◽

Preventive Treatment ◽

Intranasal Insulin ◽

Translational Repressor ◽

Beneficial Effects ◽

Underlying Mechanisms ◽

Induced Apoptosis ◽

Preclinical And Clinical Studies

AbstractLong-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.

Download Full-text

Time to Be SHY? Some Comments on Sleep and Synaptic Homeostasis

Neural Plasticity ◽

10.1155/2012/415250 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 56

Author(s):

Giulio Tononi ◽

Chiara Cirelli

Keyword(s):

Synaptic Strength ◽

Universal Function ◽

Systematic Bias ◽

Synaptic Homeostasis ◽

The Face ◽

Essential Function ◽

Function Of Sleep ◽

The Brain

Sleep must serve an essential, universal function, one that offsets the risk of being disconnected from the environment. The synaptic homeostasis hypothesis (SHY) is an attempt to identify this essential function. Its core claim is that sleep is needed to reestablish synaptic homeostasis, which is challenged by the remarkable plasticity of the brain. In other words, sleep is “the price we pay for plasticity.” In this issue, M. G. Frank reviewed several aspects of the hypothesis and raised several issues. The comments below provide a brief summary of the motivations underlying SHY and clarify that SHY is a hypothesis not about specific mechanisms, but about a universal, essential function of sleep. This function is the preservation of synaptic homeostasis in the face of a systematic bias toward a net increase in synaptic strength—a challenge that is posed by learning during adult wake, and by massive synaptogenesis during development.

Download Full-text