Persistent Enhancement of Neuron–Glia Signaling Mediated by Increased Extracellular K+ Accompanying Long-Term Synaptic Potentiation

2007 ◽  
Vol 97 (3) ◽  
pp. 2564-2569 ◽  
Author(s):  
Woo-Ping Ge ◽  
Shumin Duan
Keyword(s):  
Neuronal Activity ◽  
Neural Development ◽  
Long Term Potentiation ◽  
Nmda Receptor Antagonist ◽  
Neuronal Synapses ◽  
Term Potentiation ◽  
Physiological Relevance ◽  
Persistent Elevation ◽  
Slow Depolarization

Neuron–glia signaling is important for neural development and functions. This signaling may be regulated by neuronal activity and undergo modification similar to long-term potentiation (LTP) of neuronal synapses, a hallmark of neuronal plasticity. We found that tetanic stimulation of Schaffer collaterals (Sc) in the hippocampus that induced LTP in neurons also resulted in LTP-like persistent elevation of Sc-evoked slow depolarization in perisynaptic astrocytes. The elevated slow depolarization in astrocytes was abolished by NMDA receptor antagonist and K+ channel inhibitors, but not by Ca2+ chelator BAPTA loaded in the recorded astrocytes, suggesting involvement of an increased extracellular K+ accumulation accompanying LTP of neuronal synapses. The increased K+ accumulation and astrocyte depolarization after LTP induction may reduce the efficiency of glial glutamate transporters, which may contribute to the enhanced synaptic efficacy. The neuronal activity–induced persistent enhancement of neuron–glia signaling may thus have important physiological relevance.

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.

Neuronal activity determines the protein synthesis dependence of long-term potentiation

2006 ◽  
Vol 9 (4) ◽  
pp. 478-480 ◽  
Author(s):  
Rosalina Fonseca ◽  
U Valentin Nägerl ◽  
Tobias Bonhoeffer
Keyword(s):  
Protein Synthesis ◽  
Neuronal Activity ◽  
Long Term Potentiation ◽  
Term Potentiation

scholarly journals A physiological role for GABAA receptor desensitization – induction of long-term potentiation at inhibitory synapses

2020 ◽  
Author(s):  
Martin Field ◽  
Philip Thomas ◽  
Trevor G Smart
Keyword(s):  
Physiological Role ◽  
Long Term Potentiation ◽  
Inhibitory Synapses ◽  
Structural Basis ◽  
Inhibitory Neurotransmission ◽  
Term Potentiation ◽  
Physiological Relevance ◽  
Kinetic Effects ◽  
Physiological Impact

AbstractGABAA receptors (GABAARs) are pentameric ligand-gated ion channels distributed throughout the brain where they mediate synaptic and tonic inhibition. Following activation, these receptors undergo desensitization which involves entry into long-lived agonist-bound closed states. Although the kinetic effects of this state are recognised and its structural basis has been uncovered, the physiological impact of desensitization on inhibitory neurotransmission remains unknown. Here we describe an enduring new form of long-term potentiation at inhibitory synapses that elevates synaptic current amplitude for 24 hrs following desensitization of GABAARs in response to prolonged agonist exposure or allosteric modulation. Using receptor mutants and allosteric modulators we demonstrate that desensitization of GABAARs facilitates their phosphorylation by PKC, which increases the number of receptors at inhibitory synapses. These observations provide a new physiological relevance to the desensitized state of GABAARs, acting as a signal to regulate the efficacy of inhibitory synapses during prolonged periods of inhibitory neurotransmission.

Mechanisms underlying induction of long-term potentiation in rat medial and lateral perforant paths in vitro

1993 ◽  
Vol 69 (4) ◽  
pp. 1150-1159 ◽  
Author(s):  
A. Colino ◽  
R. C. Malenka
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Intracellular Calcium ◽  
Granule Cells ◽  
Long Term Potentiation ◽  
Nmda Receptor Antagonist ◽  
Perforant Path ◽  
Term Potentiation

1. The mechanisms underlying the induction of long-term potentiation (LTP) in the medial and lateral perforant paths were studied by recording excitatory postsynaptic potentials (EPSPs) from rat dentate granule cells in vitro using extracellular and whole-cell recording techniques. 2. Paired stimuli (interstimulus interval, 50-1,000 ms) resulted in facilitation of the lateral and depression of the medial perforant path-evoked EPSPs, respectively. This physiological difference was used to isolate responses evoked by stimulation of a single path. 3. Tetanic stimulation induced LTP in both pathways, although the magnitude of LTP in the lateral perforant path was significantly less than that in the medial perforant path. Both forms of LTP were blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV). 4. Buffering intracellular calcium by loading granule cells with the calcium chelator bis (O-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid prevented LTP in both pathways. 5. Pairing of low-frequency (0.25 Hz) afferent stimulation with postsynaptic depolarization induced LTP in the medial but not the lateral perforant path. However, pairing of higher-frequency stimulation (1-4 Hz) with postsynaptic depolarization did potentiate the lateral perforant path-evoked EPSP in some cells. 6. Both the medial and lateral perforant path-evoked EPSPs had two components; a fast component blocked by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and a slower, voltage-dependent component blocked by D-APV. 7. The results indicate that the induction of LTP in both the medial and lateral perforant paths requires activation of postsynaptic NMDA receptors and a rise in intracellular calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

The NMDA receptor antagonist Radiprodil reverses the synaptotoxic effects of different amyloid-beta (Aβ) species on long-term potentiation (LTP)

2018 ◽  
Vol 140 ◽  
pp. 184-192 ◽  
Author(s):  
Gerhard Rammes ◽  
Franziska Seeser ◽  
Korinna Mattusch ◽  
Kaichuan Zhu ◽  
Laura Haas ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Amyloid Beta ◽  
Long Term Potentiation ◽  
Nmda Receptor Antagonist ◽  
Term Potentiation
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