scholarly journals Plasticity of Neuron-Glial Transmission: Equipping Glia for Long-Term Integration of Network Activity

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Wayne Croft ◽  
Katharine L. Dobson ◽  
Tomas C. Bellamy
Keyword(s):  
Long Term Potentiation ◽  
Brain Regions ◽  
Neuronal Firing ◽  
Network Activity ◽  
Neuronal Function ◽  
Term Potentiation ◽  
Bidirectional Communication ◽  
Long Time ◽  
Activity Dependent

The capacity of synaptic networks to express activity-dependent changes in strength and connectivity is essential for learning and memory processes. In recent years, glial cells (most notably astrocytes) have been recognized as active participants in the modulation of synaptic transmission and synaptic plasticity, implicating these electrically nonexcitable cells in information processing in the brain. While the concept of bidirectional communication between neurons and glia and the mechanisms by which gliotransmission can modulate neuronal function are well established, less attention has been focussed on the computational potential of neuron-glial transmission itself. In particular, whether neuron-glial transmission is itself subject to activity-dependent plasticity and what the computational properties of such plasticity might be has not been explored in detail. In this review, we summarize current examples of plasticity in neuron-glial transmission, in many brain regions and neurotransmitter pathways. We argue that induction of glial plasticity typically requires repetitive neuronal firing over long time periods (minutes-hours) rather than the short-lived, stereotyped trigger typical of canonical long-term potentiation. We speculate that this equips glia with a mechanism for monitoring average firing rates in the synaptic network, which is suited to the longer term roles proposed for astrocytes in neurophysiology.

scholarly journals Uptake and recycling of pro-BDNF for transmitter-induced secretion by cortical astrocytes

2008 ◽  
Vol 183 (2) ◽  
pp. 213-221 ◽  
Author(s):  
Matteo Bergami ◽  
Spartaco Santi ◽  
Elena Formaggio ◽  
Cinzia Cagnoli ◽  
Claudia Verderio ◽  
...  
Keyword(s):  
Long Term Potentiation ◽  
Neurotrophin Receptor ◽  
Protein Receptor ◽  
Term Potentiation ◽  
Cultured Astrocytes ◽  
Bidirectional Communication ◽  
Specialized Form ◽  
Endocytic Vesicles ◽  
Activity Dependent

Activity-dependent secretion of brain-derived neurotrophic factor (BDNF) is thought to enhance synaptic plasticity, but the mechanisms controlling extracellular availability and clearance of secreted BDNF are poorly understood. We show that BDNF is secreted in its precursor form (pro-BDNF) and is then cleared from the extracellular space through rapid uptake by nearby astrocytes after θ-burst stimulation in layer II/III of cortical slices, a paradigm resulting in long-term potentiation of synaptic transmission. Internalization of pro-BDNF occurs via the formation of a complex with the pan-neurotrophin receptor p75 and subsequent clathrin-dependent endocytosis. Fluorescence-tagged pro-BDNF and real-time total internal reflection fluorescence microscopy in cultured astrocytes is used to monitor single endocytic vesicles in response to the neurotransmitter glutamate. We find that endocytosed pro-BDNF is routed into a fast recycling pathway for subsequent soluble NSF attachment protein receptor–dependent secretion. Thus, astrocytes contain an endocytic compartment competent for pro-BDNF recycling, suggesting a specialized form of bidirectional communication between neurons and glia.

scholarly journals Aη-α and Aη-β peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maria Mensch ◽  
Jade Dunot ◽  
Sandy M. Yishan ◽  
Samuel S. Harris ◽  
Aline Blistein ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Ex Vivo ◽  
Long Term Potentiation ◽  
Network Activity ◽  
Strongly Correlated ◽  
App Processing ◽  
Term Potentiation ◽  
Hippocampal Network

Abstract Background Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. Methods With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. Results We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo. Conclusions These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD.

The Vertical Lobe of Cephalopods

2017 ◽  
pp. 558-574 ◽  
Author(s):  
Ana Turchetti-Maia ◽  
Tal Shomrat ◽  
Binyamin Hochner
Keyword(s):  
Complex Networks ◽  
Long Term Potentiation ◽  
Learning Networks ◽  
Neuronal Circuitry ◽  
Cellular Processes ◽  
Term Potentiation ◽  
Matrix Organization ◽  
Activity Dependent ◽  
Similar Organization

We show that the cephalopod vertical lobe (VL) is a promising system for assessing the function and organization of the neuronal circuitry mediating complex learning and memory behavior. Studies in octopus and cuttlefish VL networks suggest an independent evolutionary convergence into a matrix organization of a divergence-convergence (“fan-out fan-in”) network with activity-dependent long-term plasticity mechanisms. These studies also show, however, that the properties of the neurons, neurotransmitters, neuromodulators, and mechanisms of induction and maintenance of long-term potentiation are different from those evolved in vertebrates and other invertebrates, and even highly variable among these two cephalopod species. This suggests that complex networks may have evolved independently multiple times and that, even though memory and learning networks share similar organization and cellular processes, there are many molecular ways of constructing them.

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.

Enhancement of synaptic facilitation during the progression of kindling epilepsy by amygdala stimulations

1993 ◽  
Vol 70 (2) ◽  
pp. 602-609 ◽  
Author(s):  
S. Matsuura ◽  
K. Hirayama ◽  
R. Murata
Keyword(s):  
Quantitative Analysis ◽  
Long Term Potentiation ◽  
Progressive Increase ◽  
Friedman Test ◽  
Single Test ◽  
Term Potentiation ◽  
Excitatory Component ◽  
Activity Dependent ◽  
Excitatory Potential

1. A quantitative analysis of facilitation during the kindling stimulation to the amygdala was conducted by measuring the area between the excitatory potential and the baseline in the averaged tetanic response recorded at the entorhinal cortex. The changes in facilitation were then compared with the development of electrographic afterdischarges (AD) and behavioral seizures in response to successive kindling stimulations. 2. Kindling train pulses (n = 99 or 100; duration: 0.5 ms; frequency: 10 Hz; intensity: AD threshold) were applied to conscious rats until at least one generalized seizure occurred or until 13 stimuli were delivered. 3. Facilitation of the entorhinal responses by kindling stimulation first occurred in the monosynaptic excitatory component and was then followed by a progressive increase in the polysynaptic component that was manifested as the later negative peaks. A clear progressive enhancement was observed in the facilitation by successive kindling stimulations, which also induced prolongation of the AD duration and progression of the seizure stages, indicating that activity-dependent enhancement of facilitation (EF) occurred during the progression of kindling epilepsy. 4. Quantitative analysis revealed that the EF that occurred with the progression of seizure stages was statistically significant (P < 0.001, Friedman test). The AD duration (r = 0.89) and the long-term potentiation (r = 0.85) of the entorhinal responses by single test amygdala stimuli showed a very good linear relation to the EF.(ABSTRACT TRUNCATED AT 250 WORDS)

Klk8, a multifunctional protease in the brain and skin: analysis of knockout mice

2010 ◽  
Vol 391 (4) ◽  
Author(s):  
Shigetaka Yoshida
Keyword(s):  
Central Nervous System ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
The Central Nervous System ◽  
Synaptic Changes ◽  
Adhesive Molecules ◽  
High Level ◽  
Activity Dependent ◽  
The Brain

Abstract Klk8 is a tryptic serine protease with limited substrate specificity. Klk8 mRNA is expressed in many developing organs, whereas its expression is confined to limited regions, including the hippocampus, in adults. In the hippocampus, Klk8 is involved in activity-dependent synaptic changes such as long-term potentiation, which was found to be suppressed in Klk8 knockout (KO) mice. Oligodendrocytes only expressed Klk8 mRNA after injury to the central nervous system. The epidermis of the skin is one of the tissues that exhibits a high level of KLK8 expression. Klk8 might be involved in desquamation through the degradation of adhesive molecules that connect layers of the epidermis. Klk8 might thus be involved in tissue development and rearrangement.

scholarly journals Specific Roles of AMPA Receptor Subunit GluR1 (GluA1) Phosphorylation Sites in Regulating Synaptic Plasticity in the CA1 Region of Hippocampus

2010 ◽  
Vol 103 (1) ◽  
pp. 479-489 ◽  
Author(s):  
Hey-Kyoung Lee ◽  
Kogo Takamiya ◽  
Kaiwen He ◽  
Lihua Song ◽  
Richard L. Huganir
Keyword(s):  
Synaptic Plasticity ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Phosphorylation Sites ◽  
Ca1 Region ◽  
Term Potentiation ◽  
Ampa Receptor Subunit ◽  
Glur1 Subunit ◽  
Activity Dependent

Activity-dependent changes in excitatory synaptic transmission in the CNS have been shown to depend on the regulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). In particular, several lines of evidence suggest that reversible phosphorylation of AMPAR subunit glutamate receptor 1 (GluR1, also referred to as GluA1 or GluR-A) plays a role in long-term potentiation (LTP) and long-term depression (LTD). We previously reported that regulation of serines (S) 831 and 845 on the GluR1 subunit may play a critical role in bidirectional synaptic plasticity in the Schaffer collateral inputs to CA1. Specifically, gene knockin mice lacking both S831 and S845 phosphorylation sites (“double phosphomutants”), where both serine residues were replaced by alanines (A), showed a faster decaying LTP and a deficit in LTD. To determine which of the two phosphorylation sites was responsible for the phenotype, we have now generated two lines of gene knockin mice: one that specifically lacks S831 (S831A mutants) and another that lacks only S845 (S845A mutants). We found that S831A mutants display normal LTP and LTD, whereas S845A mutants show a specific deficit in LTD. Taken together with our previous results from the “double phosphomutants,” our data suggest that either S831 or S845 alone may support LTP, whereas the S845 site is critical for LTD expression.

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