scholarly journals Energetics of stochastic BCM type synaptic plasticity and storing of accurate information

2021 ◽  
Author(s):  
Jan Karbowski
Keyword(s):  
Synaptic Plasticity ◽  
Fisher Information ◽  
Metabolic Energy ◽  
Nonlinear Dependence ◽  
General Character ◽  
Entropy Production Rate ◽  
Synaptic Current ◽  
Energy Rate ◽  
Brain Functions ◽  
Synaptic Noise

AbstractExcitatory synaptic signaling in cortical circuits is thought to be metabolically expensive. Two fundamental brain functions, learning and memory, are associated with long-term synaptic plasticity, but we know very little about energetics of these slow biophysical processes. This study investigates the energy requirement of information storing in plastic synapses for an extended version of BCM plasticity with a decay term, stochastic noise, and nonlinear dependence of neuron’s firing rate on synaptic current (adaptation). It is shown that synaptic weights in this model exhibit bistability. In order to analyze the system analytically, it is reduced to a simple dynamic mean-field for a population averaged plastic synaptic current. Next, using the concepts of nonequilibrium thermodynamics, we derive the energy rate (entropy production rate) for plastic synapses and a corresponding Fisher information for coding presynaptic input. That energy, which is of chemical origin, is primarily used for battling fluctuations in the synaptic weights and presynaptic firing rates, and it increases steeply with synaptic weights, and more uniformly though nonlinearly with presynaptic firing. At the onset of synaptic bistability, Fisher information and memory lifetime both increase sharply, by a few orders of magnitude, but the plasticity energy rate changes only mildly. This implies that a huge gain in the precision of stored information does not have to cost large amounts of metabolic energy, which suggests that synaptic information is not directly limited by energy consumption. Interestingly, for very weak synaptic noise, such a limit on synaptic coding accuracy is imposed instead by a derivative of the plasticity energy rate with respect to the mean presynaptic firing, and this relationship has a general character that is independent of the plasticity type. An estimate for primate neocortex reveals that a relative metabolic cost of BCM type synaptic plasticity, as a fraction of neuronal cost related to fast synaptic transmission and spiking, can vary from negligible to substantial, depending on the synaptic noise level and presynaptic firing.

scholarly journals Energetics of BCM type synaptic plasticity and storing of accurate information

2020 ◽  
Author(s):  
Jan Karbowski
Keyword(s):  
Synaptic Plasticity ◽  
Mean Field ◽  
Metabolic Cost ◽  
General Character ◽  
Accurate Information ◽  
Stochastic Dynamical Systems ◽  
Energy Rate ◽  
Brain Functions ◽  
Bistable Regime ◽  
Stored Information

AbstractExcitatory synaptic signaling in cortical circuits is thought to be metabolically expensive. Two fundamental brain functions, learning and memory, are associated with long-term synaptic plasticity, but we know very little about energetics of these slow biophysical processes. This study investigates the interplay between stochastic BCM type synaptic plasticity, its metabolic requirements, and the accuracy and retention of stored information in synaptic weights, within the frameworks of stochastic dynamical systems and nonequilibrium thermodynamics. The dynamic mean-field is derived for the synaptic weights, and it is found that the energy used by plastic synapses, related to their information content, is primarily caused by fluctuations in the synaptic weights and in presynaptic firing activity. Such information-related plasticity energy rate, together with the accuracy of stored information depend nonlinearly on key neurophysiological parameters, which is due to bistability in the system: synapses plus their postsynaptic neuron. At the onset of bistability, the memory lifetime, its accuracy, and plasticity energy rate are all positively correlated and exhibit sharp peaks. However, in the bistable regime, the accuracy of encoded information and plasticity energetics are generally anticorrelated, which suggests that a precise storing of synaptic information neither has to be metabolically expensive nor it is limited by energy consumption. Interestingly, such a limit on synaptic coding accuracy is imposed instead by a derivative of the plasticity energy rate with respect to the presynaptic firing, and this relationship has a general character that is independent of the plasticity type. An estimate for primate neocortex reveals that a relative metabolic cost of BCM type synaptic plasticity, as a fraction of the overall neuronal cost, can vary from negligible to substantial, depending on a synaptic working regime and presynaptic firing.

scholarly journals Monitoring and Modulating Inflammation-Associated Alterations in Synaptic Plasticity: Role of Brain Stimulation and the Blood–Brain Interface

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 359
Author(s):  
Maximilian Lenz ◽  
Amelie Eichler ◽  
Andreas Vlachos
Keyword(s):  
Synaptic Plasticity ◽  
Brain Stimulation ◽  
Vascular Function ◽  
Neuropsychiatric Symptoms ◽  
Systemic Infection ◽  
Brain Functions ◽  
Blood Brain ◽  
Brain Interface ◽  
The Central Nervous System

Inflammation of the central nervous system can be triggered by endogenous and exogenous stimuli such as local or systemic infection, trauma, and stroke. In addition to neurodegeneration and cell death, alterations in physiological brain functions are often associated with neuroinflammation. Robust experimental evidence has demonstrated that inflammatory cytokines affect the ability of neurons to express plasticity. It has been well-established that inflammation-associated alterations in synaptic plasticity contribute to the development of neuropsychiatric symptoms. Nevertheless, diagnostic approaches and interventional strategies to restore inflammatory deficits in synaptic plasticity are limited. Here, we review recent findings on inflammation-associated alterations in synaptic plasticity and the potential role of the blood–brain interface, i.e., the blood–brain barrier, in modulating synaptic plasticity. Based on recent findings indicating that brain stimulation promotes plasticity and modulates vascular function, we argue that clinically employed non-invasive brain stimulation techniques, such as transcranial magnetic stimulation, could be used for monitoring and modulating inflammation-induced alterations in synaptic plasticity.

scholarly journals Phosphorylation of the AMPAR-TARP Complex in Synaptic Plasticity

Proteomes ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 40 ◽  
Author(s):  
Joongkyu Park
Keyword(s):  
Synaptic Plasticity ◽  
Drug Addiction ◽  
Ampa Receptor ◽  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Regulatory Proteins ◽  
Cellular Models ◽  
Brain Functions ◽  
Term Potentiation

Synaptic plasticity has been considered a key mechanism underlying many brain functions including learning, memory, and drug addiction. An increase or decrease in synaptic activity of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) complex mediates the phenomena as shown in the cellular models of synaptic plasticity, long-term potentiation (LTP), and depression (LTD). In particular, protein phosphorylation shares the spotlight in expressing the synaptic plasticity. This review summarizes the studies on phosphorylation of the AMPAR pore-forming subunits and auxiliary proteins including transmembrane AMPA receptor regulatory proteins (TARPs) and discusses its role in synaptic plasticity.

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 Metabolic constraints on synaptic learning and memory

2019 ◽  
Vol 122 (4) ◽  
pp. 1473-1490 ◽  
Author(s):  
Jan Karbowski
Keyword(s):  
Synaptic Plasticity ◽  
Metabolic Rate ◽  
Protein Phosphorylation ◽  
Learning And Memory ◽  
Dendritic Spines ◽  
Energy Cost ◽  
Memory Trace ◽  
Metabolic Energy ◽  
Cascade Models ◽  
New Learning

Dendritic spines, the carriers of long-term memory, occupy a small fraction of cortical space, and yet they are the major consumers of brain metabolic energy. What fraction of this energy goes for synaptic plasticity, correlated with learning and memory? It is estimated here based on neurophysiological and proteomic data for rat brain that, depending on the level of protein phosphorylation, the energy cost of synaptic plasticity constitutes a small fraction of the energy used for fast excitatory synaptic transmission, typically 4.0–11.2%. Next, this study analyzes a metabolic cost of new learning and its memory trace in relation to the cost of prior memories, using a class of cascade models of synaptic plasticity. It is argued that these models must contain bidirectional cyclic motifs, related to protein phosphorylation, to be compatible with basic thermodynamic principles. For most investigated parameters longer memories generally require proportionally more energy to store. The exceptions are the parameters controlling the speed of molecular transitions (e.g., ATP-driven phosphorylation rate), for which memory lifetime per invested energy can increase progressively for longer memories. Furthermore, in general, a memory trace decouples dynamically from a corresponding synaptic metabolic rate such that the energy expended on new learning and its memory trace constitutes in most cases only a small fraction of the baseline energy associated with prior memories. Taken together, these empirical and theoretical results suggest a metabolic efficiency of synaptically stored information. NEW & NOTEWORTHY Learning and memory involve a sequence of molecular events in dendritic spines called synaptic plasticity. These events are physical in nature and require energy, which has to be supplied by ATP molecules. However, our knowledge of the energetics of these processes is very poor. This study estimates the empirical energy cost of synaptic plasticity and considers theoretically a metabolic rate of learning and its memory trace in a class of cascade models of synaptic plasticity.

scholarly journals Neural inflammation alters synaptic plasticity probed by 10 Hz repetitive magnetic stimulation

2020 ◽  
Author(s):  
Maximilian Lenz ◽  
Amelie Eichler ◽  
Pia Kruse ◽  
Andreas Strehl ◽  
Silvia Rodriguez-Rozada ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Systemic Inflammation ◽  
Magnetic Stimulation ◽  
Long Term Potentiation ◽  
Brain Inflammation ◽  
Suitable Model ◽  
Tissue Cultures ◽  
Brain Functions ◽  
Repetitive Magnetic Stimulation ◽  
Excitatory Neurotransmission

ABSTRACTSystemic inflammation is associated with alterations in complex brain functions such as learning and memory. However, diagnostic approaches to functionally assess and quantify inflammation-associated alterations in synaptic plasticity are not well-established. In previous work, we demonstrated that bacterial lipopolysaccharide (LPS)-induced systemic inflammation alters the ability of hippocampal neurons to express synaptic plasticity, i.e., the long-term potentiation (LTP) of excitatory neurotransmission. Here, we tested whether synaptic plasticity induced by repetitive magnetic stimulation (rMS), a non-invasive brain stimulation technique used in clinical practice, is affected by LPS-induced inflammation. Specifically, we explored brain tissue cultures to learn more about the direct effects of LPS on neural tissue, and we tested for the plasticity-restoring effects of the anti-inflammatory cytokine interleukin 10 (IL10). As shown previously, 10 Hz repetitive magnetic stimulation (rMS) of organotypic entorhino-hippocampal tissue cultures induced a robust increase in excitatory neurotransmission onto CA1 pyramidal neurons. Furthermore, LPS-treated tissue cultures did not express rMS-induced synaptic plasticity. Live-cell microscopy in tissue cultures prepared from a novel transgenic reporter mouse line [C57BL6-Tg(TNFa-eGFP)] confirms that ex vivo LPS administration triggers microglial tumor necrosis factor alpha (TNFα) expression, which is ameliorated in the presence of IL10. Consistent with this observation, IL10 hampers the LPS-induced increase in TNFα, IL6, IL1β, and IFNγ and restores the ability of neurons to express rMS-induced synaptic plasticity in the presence of LPS. These findings establish organotypic tissue cultures as a suitable model for studying inflammation-induced alterations in synaptic plasticity, thus providing a biological basis for the diagnostic use of transcranial magnetic stimulation in the context of brain inflammation.

scholarly journals Stress-Sensitive Protein Rac1 and Its Involvement in Neurodevelopmental Disorders

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xiaohui Wang ◽  
Dongbin Liu ◽  
Fangzhen Wei ◽  
Yue Li ◽  
Xuefeng Wang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Neurodevelopmental Disorders ◽  
Neurological Diseases ◽  
Small Gtpase ◽  
Actin Dynamics ◽  
Downstream Signaling ◽  
Cellular Processes ◽  
Brain Functions ◽  
Oxidative Products ◽  
External Signals

Ras-related C3 botulinum toxin substrate 1 (Rac1) is a small GTPase that is well known for its sensitivity to the environmental stress of a cell or an organism. It senses the external signals which are transmitted from membrane-bound receptors and induces downstream signaling cascades to exert its physiological functions. Rac1 is an important regulator of a variety of cellular processes, such as cytoskeletal organization, generation of oxidative products, and gene expression. In particular, Rac1 has a significant influence on certain brain functions like neuronal migration, synaptic plasticity, and memory formation via regulation of actin dynamics in neurons. Abnormal Rac1 expression and activity have been observed in multiple neurological diseases. Here, we review recent findings to delineate the role of Rac1 signaling in neurodevelopmental disorders associated with abnormal spine morphology, synaptogenesis, and synaptic plasticity. Moreover, certain novel inhibitors of Rac1 and related pathways are discussed as potential avenues toward future treatment for these diseases.

scholarly journals Regulation of synaptic functions in central nervous system by endocrine hormones and the maintenance of energy homoeostasis

2012 ◽  
Vol 32 (5) ◽  
pp. 423-432 ◽  
Author(s):  
Zhiping P. Pang ◽  
Weiping Han
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Synaptic Plasticity ◽  
Current Knowledge ◽  
Physiological Regulation ◽  
Brain Functions ◽  
Synaptic Functions ◽  
Brain Circuitry ◽  
Pathological Development ◽  
Hormone Signals

Energy homoeostasis, a co-ordinated balance of food intake and energy expenditure, is regulated by the CNS (central nervous system). The past decade has witnessed significant advances in our understanding of metabolic processes and brain circuitry which responds to a broad range of neural, nutrient and hormonal signals. Accumulating evidence demonstrates altered synaptic plasticity in the CNS in response to hormone signals. Moreover, emerging observations suggest that synaptic plasticity underlies all brain functions, including the physiological regulation of energy homoeostasis, and that impaired synaptic constellation and plasticity may lead to pathological development and conditions. Here, we summarize the current knowledge on the regulation of postsynaptic receptors such as AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid), NMDA (N-methyl-D-aspartate) and GABA (γ-aminobutyric acid) receptors, and the presynaptic components by hormone signals. A detailed understanding of the neurobiological mechanisms by which hormones regulate energy homoeostasis may lead to novel strategies in treating metabolic disorders.

scholarly journals Interleukin 10 Restores Lipopolysaccharide-Induced Alterations in Synaptic Plasticity Probed by Repetitive Magnetic Stimulation

2020 ◽  
Vol 11 ◽  
Author(s):  
Maximilian Lenz ◽  
Amelie Eichler ◽  
Pia Kruse ◽  
Andreas Strehl ◽  
Silvia Rodriguez-Rozada ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Systemic Inflammation ◽  
Magnetic Stimulation ◽  
Long Term Potentiation ◽  
Interleukin 10 ◽  
Brain Inflammation ◽  
Tissue Cultures ◽  
Brain Functions ◽  
Repetitive Magnetic Stimulation ◽  
Excitatory Neurotransmission

Systemic inflammation is associated with alterations in complex brain functions such as learning and memory. However, diagnostic approaches to functionally assess and quantify inflammation-associated alterations in synaptic plasticity are not well-established. In previous work, we demonstrated that bacterial lipopolysaccharide (LPS)-induced systemic inflammation alters the ability of hippocampal neurons to express synaptic plasticity, i.e., the long-term potentiation (LTP) of excitatory neurotransmission. Here, we tested whether synaptic plasticity induced by repetitive magnetic stimulation (rMS), a non-invasive brain stimulation technique used in clinical practice, is affected by LPS-induced inflammation. Specifically, we explored brain tissue cultures to learn more about the direct effects of LPS on neural tissue, and we tested for the plasticity-restoring effects of the anti-inflammatory cytokine interleukin 10 (IL10). As shown previously, 10 Hz repetitive magnetic stimulation (rMS) of organotypic entorhino-hippocampal tissue cultures induced a robust increase in excitatory neurotransmission onto CA1 pyramidal neurons. Furthermore, LPS-treated tissue cultures did not express rMS-induced synaptic plasticity. Live-cell microscopy in tissue cultures prepared from a novel transgenic reporter mouse line [C57BL/6-Tg(TNFa-eGFP)] confirms that ex vivo LPS administration triggers microglial tumor necrosis factor alpha (TNFα) expression, which is ameliorated in the presence of IL10. Consistent with this observation, IL10 hampers the LPS-induced increase in TNFα, IL6, IL1β, and IFNγ and restores the ability of neurons to express rMS-induced synaptic plasticity in the presence of LPS. These findings establish organotypic tissue cultures as a suitable model for studying inflammation-induced alterations in synaptic plasticity, thus providing a biological basis for the diagnostic use of transcranial magnetic stimulation in the context of brain inflammation.

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