scholarly journals Wherefore Art Thou, Homeo(stasis)? Functional Diversity in Homeostatic Synaptic Plasticity

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Bridget N. Queenan ◽  
Kea Joo Lee ◽  
Daniel T. S. Pak
Keyword(s):  
Synaptic Plasticity ◽  
Homeostatic Plasticity ◽  
Network Activity ◽  
Control Mechanisms ◽  
Adaptive Responses ◽  
Neuronal Function ◽  
Homeostatic Synaptic Plasticity ◽  
Regulatory Principle ◽  
Functional Classes ◽  
Homeostatic Mechanisms

Homeostatic plasticity has emerged as a fundamental regulatory principle that strives to maintain neuronal activity within optimal ranges by altering diverse aspects of neuronal function. Adaptation to network activity is often viewed as an essential negative feedback restraint that prevents runaway excitation or inhibition. However, the precise importance of these homeostatic functions is often theoretical rather than empirically derived. Moreover, a remarkable multiplicity of homeostatic adaptations has been observed. To clarify these issues, it may prove useful to ask: why do homeostatic mechanisms exist, what advantages do these adaptive responses confer on a given cell population, and why are there so many seemingly divergent effects? Here, we approach these questions by applying the principles of control theory to homeostatic synaptic plasticity of mammalian neurons and suggest that the varied responses observed may represent distinct functional classes of control mechanisms directed toward disparate physiological goals.

scholarly journals Modulation of network activity and induction of homeostatic synaptic plasticity by enzymatic removal of heparan sulfates

2014 ◽  
Vol 369 (1654) ◽  
pp. 20140134 ◽  
Author(s):  
Svetlana Korotchenko ◽  
Lorenzo A. Cingolani ◽  
Tatiana Kuznetsova ◽  
Luca Leonardo Bologna ◽  
Michela Chiappalone ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Network Activity ◽  
Strong Increase ◽  
Bioelectrical Activity ◽  
Highly Active ◽  
Homeostatic Synaptic Plasticity ◽  
Term Potentiation ◽  
Heparan Sulfates

Heparan sulfates (HSs) are complex and highly active molecules that are required for synaptogenesis and long-term potentiation. A deficit in HSs leads to autistic phenotype in mice. Here, we investigated the long-term effect of heparinase I, which digests highly sulfated HSs, on the spontaneous bioelectrical activity of neuronal networks in developing primary hippocampal cultures. We found that chronic heparinase treatment led to a significant reduction of the mean firing rate of neurons, particularly during the period of maximal neuronal activity. Furthermore, firing pattern in heparinase-treated cultures often appeared as epileptiform bursts, with long periods of inactivity between them. These changes in network activity were accompanied by an increase in the frequency and amplitude of miniature postsynaptic excitatory currents, which could be described by a linear up-scaling of current amplitudes. Biochemically, we observed an upregulation in the expression of the glutamate receptor subunit GluA1, but not GluA2, and a strong increase in autophosphorylation of α and β Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), without changes in the levels of kinase expression. These data suggest that a deficit in HSs triggers homeostatic synaptic plasticity and drastically affects functional maturation of neural network.

scholarly journals Homeostatic Plasticity Hypothesis and Mechanisms of Neocortical Epilepsies

2005 ◽  
Vol 5 (4) ◽  
pp. 133-135 ◽  
Author(s):  
Jaideep Kapur ◽  
Stacey Trotter
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Activity ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Homeostatic Plasticity ◽  
Excitatory Synapses ◽  
Excitatory Postsynaptic Currents ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Homeostatic Synaptic Plasticity

Homeostatic Synaptic Plasticity Can Explain Posttraumatic Epileptogenesis in Chronically Isolated Neocortex Houweling AR, Bazhenov M, Timofeev I, Steriade M, Sejnowski TJ Cereb Cortex 2004 [Epub ahead of print] Permanently isolated neocortex develops chronic hyperexcitability and focal epileptogenesis in a period of days to weeks. The mechanisms operating in this model of posttraumatic epileptogenesis are not well understood. We hypothesized that the spontaneous burst discharges recorded in permanently isolated neocortex result from homeostatic plasticity (a mechanism generally assumed to stabilize neuronal activity) induced by low neuronal activity after deafferentation. To test this hypothesis, we constructed computer models of neocortex incorporating a biologically based homeostatic plasticity rule that operates to maintain firing rates. After deafferentation, homeostatic upregulation of excitatory synapses on pyramidal cells, either with or without concurrent downregulation of inhibitory synapses or upregulation of intrinsic excitability, initiated slowly repeating burst discharges that closely resembled the epileptiform burst discharges recorded in permanently isolated neocortex. These burst discharges lasted a few hundred milliseconds, propagated at 1 to 3 cm/s and consisted of large (10–15 mV) intracellular depolarizations topped by a small number of action potentials. Our results support a role for homeostatic synaptic plasticity as a novel mechanism of posttraumatic epileptogenesis. Excitatory and Inhibitory Postsynaptic Currents in a Rat Model of Epileptogenic Microgyria Jacobs KM, Prince DA J Neurophysiol 2005;93:687–696 Developmental cortical malformations are common in patients with intractable epilepsy; however, mechanisms contributing to this epileptogenesis are currently poorly understood. We previously characterized hyperexcitability in a rat model that mimics the histopathology of human four-layered microgyria. Here we examined inhibitory and excitatory postsynaptic currents in this model to identify functional alterations that might contribute to epileptogenesis associated with microgyria. We recorded isolated whole-cell excitatory postsynaptic currents and GABAA receptor–mediated inhibitory currents from layer V pyramidal neurons in the region previously shown to be epileptogenic (paramicrogyral area) and in homotopic control cortex. Epileptiform-like activity could be evoked in 60% of paramicrogyral (PMG) cells by local stimulation. The peak conductance of both spontaneous and evoked inhibitory postsynaptic currents was significantly larger in all PMG cells compared with controls. This difference in amplitude was not present after blockade of ionotropic glutamatergic currents or for miniature (m) inhibitory postsynaptic currents, suggesting that it was due to the excitatory afferent activity driving inhibitory neurons. This conclusion was supported by the finding that glutamatereceptor antagonist application resulted in a significantly greater reduction in spontaneous inhibitory postsynaptic current frequency in one PMG cell group (PMGE) compared with control cells. The frequency of both spontaneous and miniature excitatory postsynaptic currents was significantly greater in all PMG cells, suggesting that pyramidal neurons adjacent to a microgyrus receive more excitatory input than do those in control cortex. These findings suggest that there is an increase in numbers of functional excitatory synapses on both interneurons and pyramidal cells in the PMG cortex, perhaps due to hyperinnervation by cortical afferents originally destined for the microgyrus proper.

scholarly journals Voltage-based inhibitory synaptic plasticity: network regulation, diversity, and flexibility

2020 ◽  
Author(s):  
Victor Pedrosa ◽  
Claudia Clopath
Keyword(s):  
Synaptic Plasticity ◽  
Pyramidal Cell ◽  
Brain Regions ◽  
Postsynaptic Membrane ◽  
Network Activity ◽  
Inhibitory Neurons ◽  
Plasticity Model ◽  
Feedforward Network ◽  
Voltage Dependent ◽  
Homeostatic Mechanisms

AbstractNeural networks are highly heterogeneous while homeostatic mechanisms ensure that this heterogeneity is kept within a physiologically safe range. One of such homeostatic mechanisms, inhibitory synaptic plasticity, has been observed across different brain regions. Computationally, however, inhibitory synaptic plasticity models often lead to a strong suppression of neuronal diversity. Here, we propose a model of inhibitory synaptic plasticity in which synaptic updates depend on presynaptic spike arrival and postsynaptic membrane voltage. Our plasticity rule regulates the network activity by setting a target value for the postsynaptic membrane potential over a long timescale. In a feedforward network, we show that our voltage-dependent inhibitory synaptic plasticity (vISP) model regulates the excitatory/inhibitory ratio while allowing for a broad range of postsynaptic firing rates and thus network diversity. In a feedforward network in which excitatory and inhibitory neurons receive correlated input, our plasticity model allows for the development of co-tuned excitation and inhibition, in agreement with recordings in rat auditory cortex. In recurrent networks, our model supports memory formation and retrieval while allowing for the development of heterogeneous neuronal activity. Finally, we implement our vISP rule in a model of the hippocampal CA1 region whose pyramidal cell excitability differs across cells. This model accounts for the experimentally observed variability in pyramidal cell features such as the number of place fields, the fields sizes, and the portion of the environment covered by each cell. Importantly, our model supports a combination of sparse and dense coding in the hippocampus. Therefore, our voltage-dependent inhibitory plasticity model accounts for network homeostasis while allowing for diverse neuronal dynamics observed across brain regions.

scholarly journals Amyloid-beta mediates homeostatic synaptic plasticity

2020 ◽  
Author(s):  
Christos Galanis ◽  
Meike Fellenz ◽  
Denise Becker ◽  
Charlotte Bold ◽  
Stefan F. Lichtenthaler ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Granule Cells ◽  
Amyloid Β ◽  
Physiological Role ◽  
Homeostatic Plasticity ◽  
App Processing ◽  
Brain Physiology ◽  
Homeostatic Synaptic Plasticity ◽  
Organotypic Tissue

ABSTRACTThe physiological role of the amyloid-precursor protein (APP) is insufficiently understood. Recent work has implicated APP in the regulation of synaptic plasticity. Substantial evidence exists for a role of APP and its secreted ectodomain APPsα in Hebbian plasticity. Here, we addressed the relevance of APP in homeostatic synaptic plasticity using organotypic tissue cultures of APP−/− mice. In the absence of APP, dentate granule cells failed to strengthen their excitatory synapses homeostatically. Homeostatic plasticity is rescued by amyloid-β (Aβ) and not by APPsα, and it is neither observed in APP+/+ tissue treated with β- or γ-secretase inhibitors nor in synaptopodin-deficient cultures lacking the Ca2+-dependent molecular machinery of the spine apparatus. Together, these results suggest a role of APP processing via the amyloidogenic pathway in homeostatic synaptic plasticity, representing a function of relevance for brain physiology as well as for brain states associated with increased Aβ levels.

scholarly journals Borna Disease Virus Infection Impairs Synaptic Plasticity

2007 ◽  
Vol 81 (16) ◽  
pp. 8833-8837 ◽  
Author(s):  
Romain Volmer ◽  
Christine M. A. Prat ◽  
Gwendal Le Masson ◽  
André Garenne ◽  
Daniel Gonzalez-Dunia
Keyword(s):  
Synaptic Plasticity ◽  
Disease Virus ◽  
Network Activity ◽  
Multielectrode Arrays ◽  
Neuronal Function ◽  
Borna Disease Virus ◽  
Electrophysiological Properties ◽  
Neuronal Network Activity ◽  
Activity Dependent ◽  
Borna Disease

ABSTRACT The mechanisms whereby Borna disease virus (BDV) can impair neuronal function and lead to neurobehavioral disease are not well understood. To analyze the electrophysiological properties of neurons infected with BDV, we used cultures of neurons grown on multielectrode arrays, allowing a real-time monitoring of the electrical activity across the network shaped by synaptic transmission. Although infection did not affect spontaneous neuronal activity, it selectively blocked activity-dependent enhancement of neuronal network activity, one form of synaptic plasticity thought to be important for learning and memory. These findings highlight the original mechanism of the neuronal dysfunction caused by noncytolytic infection with BDV.

scholarly journals AMPA Receptor Trafficking in Homeostatic Synaptic Plasticity: Functional Molecules and Signaling Cascades

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Guan Wang ◽  
James Gilbert ◽  
Heng-Ye Man
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Firing ◽  
Synaptic Activity ◽  
Homeostatic Plasticity ◽  
Signaling Cascades ◽  
Excitatory Synapses ◽  
Homeostatic Synaptic Plasticity ◽  
Ampar Trafficking ◽  
Entire Network ◽  
Homeostatic Response

Homeostatic synaptic plasticity is a negative-feedback response employed to compensate for functional disturbances in the nervous system. Typically, synaptic activity is strengthened when neuronal firing is chronically suppressed or weakened when neuronal activity is chronically elevated. At both the whole cell and entire network levels, activity manipulation leads to a global up- or downscaling of the transmission efficacy of all synapses. However, the homeostatic response can also be induced locally at subcellular regions or individual synapses. Homeostatic synaptic scaling is expressed mainly via the regulation ofα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking and synaptic expression. Here we review the recently identified functional molecules and signaling pathways that are involved in homeostatic plasticity, especially the homeostatic regulation of AMPAR localization at excitatory synapses.

scholarly journals FMRP Interacts with RARα in Synaptic Retinoic Acid Signaling and Homeostatic Synaptic Plasticity

2021 ◽  
Vol 22 (12) ◽  
pp. 6579
Author(s):  
Esther Park ◽  
Anthony G. Lau ◽  
Kristin L. Arendt ◽  
Lu Chen
Keyword(s):  
Mental Retardation ◽  
Retinoic Acid ◽  
Synaptic Plasticity ◽  
Fragile X ◽  
Neurodevelopmental Disorder ◽  
Synaptic Function ◽  
Homeostatic Plasticity ◽  
Fragile X Mental Retardation ◽  
Severe Intellectual Disability ◽  
Homeostatic Synaptic Plasticity

The fragile X syndrome (FXS) is an X-chromosome-linked neurodevelopmental disorder with severe intellectual disability caused by inactivation of the fragile X mental retardation 1 (FMR1) gene and subsequent loss of the fragile X mental retardation protein (FMRP). Among the various types of abnormal synaptic function and synaptic plasticity phenotypes reported in FXS animal models, defective synaptic retinoic acid (RA) signaling and subsequent defective homeostatic plasticity have emerged as a major synaptic dysfunction. However, the mechanism underlying the defective synaptic RA signaling in the absence of FMRP is unknown. Here, we show that RARα, the RA receptor critically involved in synaptic RA signaling, directly interacts with FMRP. This interaction is enhanced in the presence of RA. Blocking the interaction between FMRP and RARα with a small peptide corresponding to the critical binding site in RARα abolishes RA-induced increases in excitatory synaptic transmission, recapitulating the phenotype seen in the Fmr1 knockout mouse. Taken together, these data suggest that not only are functional FMRP and RARα necessary for RA-dependent homeostatic synaptic plasticity, but that the interaction between these two proteins is essential for proper transcription-independent RA signaling. Our results may provide further mechanistic understanding into FXS synaptic pathophysiology.

scholarly journals Synaptic retinoic acid receptor signaling mediates mTOR-dependent metaplasticity that controls hippocampal learning

2019 ◽  
Vol 116 (14) ◽  
pp. 7113-7122 ◽  
Author(s):  
Yu-Tien Hsu ◽  
Jie Li ◽  
Dick Wu ◽  
Thomas C. Südhof ◽  
Lu Chen
Keyword(s):  
Retinoic Acid ◽  
Synaptic Plasticity ◽  
Retinoic Acid Receptor ◽  
Protein Translation ◽  
Receptor Expression ◽  
Network Activity ◽  
Expression Levels ◽  
Acid Receptor ◽  
Homeostatic Synaptic Plasticity ◽  
Hebbian Plasticity

Homeostatic synaptic plasticity is a stabilizing mechanism engaged by neural circuits in response to prolonged perturbation of network activity. The non-Hebbian nature of homeostatic synaptic plasticity is thought to contribute to network stability by preventing “runaway” Hebbian plasticity at individual synapses. However, whether blocking homeostatic synaptic plasticity indeed induces runaway Hebbian plasticity in an intact neural circuit has not been explored. Furthermore, how compromised homeostatic synaptic plasticity impacts animal learning remains unclear. Here, we show in mice that the experience of an enriched environment (EE) engaged homeostatic synaptic plasticity in hippocampal circuits, thereby reducing excitatory synaptic transmission. This process required RARα, a nuclear retinoic acid receptor that doubles as a cytoplasmic retinoic acid-induced postsynaptic regulator of protein synthesis. Blocking RARα-dependent homeostatic synaptic plasticity during an EE experience by ablating RARα signaling induced runaway Hebbian plasticity, as evidenced by greatly enhanced long-term potentiation (LTP). As a consequence, RARα deletion in hippocampal circuits during an EE experience resulted in enhanced spatial learning but suppressed learning flexibility. In the absence of RARα, moreover, EE experience superactivated mammalian target of rapamycin (mTOR) signaling, causing a shift in protein translation that enhanced the expression levels of AMPA-type glutamate receptors. Treatment of mice with the mTOR inhibitor rapamycin during an EE experience not only restored normal AMPA-receptor expression levels but also reversed the increases in runaway Hebbian plasticity and learning after hippocampal RARα deletion. Thus, our findings reveal an RARα- and mTOR-dependent mechanism by which homeostatic plasticity controls Hebbian plasticity and learning.

scholarly journals Hebbian plasticity requires compensatory processes on multiple timescales

2017 ◽  
Vol 372 (1715) ◽  
pp. 20160259 ◽  
Author(s):  
Friedemann Zenke ◽  
Wulfram Gerstner
Keyword(s):  
Synaptic Plasticity ◽  
Experimental Research ◽  
Neural Circuits ◽  
Homeostatic Plasticity ◽  
Fine Tuning ◽  
Control Mechanisms ◽  
Network Stability ◽  
Multiple Timescales ◽  
Hebbian Plasticity ◽  
Compensatory Process

We review a body of theoretical and experimental research on Hebbian and homeostatic plasticity, starting from a puzzling observation: while homeostasis of synapses found in experiments is a slow compensatory process, most mathematical models of synaptic plasticity use rapid compensatory processes (RCPs). Even worse, with the slow homeostatic plasticity reported in experiments, simulations of existing plasticity models cannot maintain network stability unless further control mechanisms are implemented. To solve this paradox, we suggest that in addition to slow forms of homeostatic plasticity there are RCPs which stabilize synaptic plasticity on short timescales. These rapid processes may include heterosynaptic depression triggered by episodes of high postsynaptic firing rate. While slower forms of homeostatic plasticity are not sufficient to stabilize Hebbian plasticity, they are important for fine-tuning neural circuits. Taken together we suggest that learning and memory rely on an intricate interplay of diverse plasticity mechanisms on different timescales which jointly ensure stability and plasticity of neural circuits. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.

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