scholarly journals Amyloid Beta Peptides Differentially Affect Hippocampal Theta Rhythms In Vitro

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Armando I. Gutiérrez-Lerma ◽  
Benito Ordaz ◽  
Fernando Peña-Ortega
Keyword(s):  
Amyloid Beta ◽  
Neuronal Network ◽  
Hippocampal Slices ◽  
Network Activity ◽  
Oscillatory Activity ◽  
High Concentration ◽  
Cellular Mechanisms ◽  
Experimental Conditions ◽  
Hippocampal Theta

Soluble amyloid beta peptide (Aβ) is responsible for the early cognitive dysfunction observed in Alzheimer's disease. Both cholinergically and glutamatergically induced hippocampal theta rhythms are related to learning and memory, spatial navigation, and spatial memory. However, these two types of theta rhythms are not identical; they are associated with different behaviors and can be differentially modulated by diverse experimental conditions. Therefore, in this study, we aimed to investigate whether or not application of soluble Aβ alters the two types of theta frequency oscillatory network activity generated in rat hippocampal slices by application of the cholinergic and glutamatergic agonists carbachol or DHPG, respectively. Due to previous evidence that oscillatory activity can be differentially affected by different Aβ peptides, we also compared Aβ25−35 and Aβ1−42 for their effects on theta rhythms in vitro at similar concentrations (0.5 to 1.0 μM). We found that Aβ25−35 reduces, with less potency than Aβ1−42, carbachol-induced population theta oscillatory activity. In contrast, DHPG-induced oscillatory activity was not affected by a high concentration of Aβ25−35 but was reduced by Aβ1−42. Our results support the idea that different amyloid peptides might alter specific cellular mechanisms related to the generation of specific neuronal network activities, instead of exerting a generalized inhibitory effect on neuronal network function.

Amyloid beta modulation of neuronal network activity in vitro

2015 ◽  
Vol 1629 ◽  
pp. 1-9 ◽  
Author(s):  
Hamid Charkhkar ◽  
Susheela Meyyappan ◽  
Evgenia Matveeva ◽  
Jonathan R. Moll ◽  
Daniel G. McHail ◽  
...  
Keyword(s):  
Amyloid Beta ◽  
Neuronal Network ◽  
Network Activity ◽  
Neuronal Network Activity

Fast Network Oscillations in the Rat Dentate Gyrus In Vitro

2002 ◽  
Vol 87 (2) ◽  
pp. 1165-1168 ◽  
Author(s):  
Stephen K. Towers ◽  
Fiona E. N. LeBeau ◽  
Tengis Gloveli ◽  
Roger D. Traub ◽  
Miles A. Whittington ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Hippocampal Formation ◽  
Molecular Layer ◽  
Hippocampal Slices ◽  
Network Activity ◽  
Oscillatory Activity ◽  
Gamma Frequency ◽  
Fast Network

The dentate gyrus is a prominent source of gamma frequency activity in the hippocampal formation in vivo. Here we show that transient epochs of gamma frequency network activity (67 ± 12 Hz) can be generated in the dentate gyrus of rat hippocampal slices, following brief pressure ejections of a high-molarity potassium solution onto the molecular layer. Oscillatory activity remains synchronized over distances >300 μm and is accompanied by a modest rise in [K+]o. Gamma frequency oscillations were abolished by a GABAA receptor antagonist demonstrating their dependence on rhythmic inhibition. However, in many cases, higher frequency oscillations (>80 Hz) remained in the absence of synaptic transmission, thus demonstrating that nonsynaptic factors may underlie fast oscillatory activity.

Dementia with Lewy bodies—associated ß-synuclein mutations V70M and P123H cause mutation-specific neuropathological lesions

2021 ◽  
Author(s):  
Maryna Psol ◽  
Sofia Guerin Darvas ◽  
Kristian Leite ◽  
Sameehan U Mahajani ◽  
Mathias Bähr ◽  
...  
Keyword(s):  
Neuronal Network ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Sporadic Case ◽  
Network Activity ◽  
Proteinase K ◽  
Neuronal Network Activity ◽  
Distinct Disease

Abstract ß-Synuclein (ß-Syn) has long been considered to be an attenuator for the neuropathological effects caused by the Parkinson’s disease-related α-Synuclein (α-Syn) protein. However, recent studies demonstrated that overabundant ß-Syn can form aggregates and induce neurodegeneration in CNS neurons in vitro and in vivo, albeit at a slower pace as compared to α-Syn. Here we demonstrate that ß-Syn mutants V70M, detected in a sporadic case of Dementia with Lewy Bodies (DLB), and P123H, detected in a familial case of DLB, robustly aggravate the neurotoxic potential of ß-Syn. Intriguingly, the two mutations trigger mutually exclusive pathways. ß-Syn V70M enhances morphological mitochondrial deterioration and degeneration of dopaminergic and non-dopaminergic neurons, but has no influence on neuronal network activity. Conversely, ß-Syn P123H silences neuronal network activity, but does not aggravate neurodegeneration. ß-Syn WT, V70M and P123H formed proteinase K (PK) resistant intracellular fibrils within neurons, albeit with less stable C-termini as compared to α-Syn. Under cell free conditions, ß-Syn V70M demonstrated a much slower pace of fibril formation as compared to WT ß-Syn, and P123H fibrils present with a unique phenotype characterized by large numbers of short, truncated fibrils. Thus, it is possible that V70M and P123H cause structural alterations in ß-Syn, that are linked to their distinct neuropathological profiles. The extent of the lesions caused by these neuropathological profiles is almost identical to that of overabundant α-Syn, and thus likely to be directly involved into etiology of DLB. Over all, this study provides insights into distinct disease mechanisms caused by mutations of ß-Syn.

Influence of albumin dialysis (MARS) on neuronal network activity in vitro

2001 ◽  
Vol 39 ◽  
pp. 40-40
Author(s):  
J Loock ◽  
J Stange ◽  
S Mitzner ◽  
R Schmidt ◽  
E W Keefer ◽  
...  
Keyword(s):  
Neuronal Network ◽  
Network Activity ◽  
Albumin Dialysis ◽  
Neuronal Network Activity

scholarly journals Pharmacological intervention to restore connectivity deficits of neuronal networks derived from ASD patient iPSC with a TSC2 mutation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mouhamed Alsaqati ◽  
Vivi M. Heine ◽  
Adrian J. Harwood
Keyword(s):  
Neuronal Network ◽  
Electrode Array ◽  
Network Connectivity ◽  
Autism Spectrum ◽  
Network Activity ◽  
Inhibitory Synapses ◽  
Pharmacological Intervention ◽  
Spatial Connectivity ◽  
Neuronal Network Activity

Abstract Background Tuberous sclerosis complex (TSC) is a rare genetic multisystemic disorder resulting from autosomal dominant mutations in the TSC1 or TSC2 genes. It is characterised by hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway and has severe neurodevelopmental and neurological components including autism, intellectual disability and epilepsy. In human and rodent models, loss of the TSC proteins causes neuronal hyperexcitability and synaptic dysfunction, although the consequences of these changes for the developing central nervous system are currently unclear. Methods Here we apply multi-electrode array-based assays to study the effects of TSC2 loss on neuronal network activity using autism spectrum disorder (ASD) patient-derived iPSCs. We examine both temporal synchronisation of neuronal bursting and spatial connectivity between electrodes across the network. Results We find that ASD patient-derived neurons with a functional loss of TSC2, in addition to possessing neuronal hyperactivity, develop a dysfunctional neuronal network with reduced synchronisation of neuronal bursting and lower spatial connectivity. These deficits of network function are associated with elevated expression of genes for inhibitory GABA signalling and glutamate signalling, indicating a potential abnormality of synaptic inhibitory–excitatory signalling. mTORC1 activity functions within a homeostatic triad of protein kinases, mTOR, AMP-dependent protein Kinase 1 (AMPK) and Unc-51 like Autophagy Activating Kinase 1 (ULK1) that orchestrate the interplay of anabolic cell growth and catabolic autophagy while balancing energy and nutrient homeostasis. The mTOR inhibitor rapamycin suppresses neuronal hyperactivity, but does not increase synchronised network activity, whereas activation of AMPK restores some aspects of network activity. In contrast, the ULK1 activator, LYN-1604, increases the network behaviour, shortens the network burst lengths and reduces the number of uncorrelated spikes. Limitations Although a robust and consistent phenotype is observed across multiple independent iPSC cultures, the results are based on one patient. There may be more subtle differences between patients with different TSC2 mutations or differences of polygenic background within their genomes. This may affect the severity of the network deficit or the pharmacological response between TSC2 patients. Conclusions Our observations suggest that there is a reduction in the network connectivity of the in vitro neuronal network associated with ASD patients with TSC2 mutation, which may arise via an excitatory/inhibitory imbalance due to increased GABA-signalling at inhibitory synapses. This abnormality can be effectively suppressed via activation of ULK1.

scholarly journals Bidirectional in vivo structural dendritic spine plasticity revealed by two-photon glutamate uncaging in the mouse neocortex

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jun Noguchi ◽  
Akira Nagaoka ◽  
Tatsuya Hayama ◽  
Hasan Ucar ◽  
Sho Yagishita ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Time Course ◽  
Hippocampal Slices ◽  
Low Frequency ◽  
Structural Plasticity ◽  
Experimental Conditions ◽  
Two Photon ◽  
Spine Plasticity

Abstract Most excitatory synapses in the brain form on dendritic spines. Two-photon uncaging of glutamate is widely utilized to characterize the structural plasticity of dendritic spines in brain slice preparations in vitro. In the present study, glutamate uncaging was used to investigate spine plasticity, for the first time, in vivo. A caged glutamate compound was applied to the surface of the mouse visual cortex in vivo, revealing the successful induction of spine enlargement by repetitive two-photon uncaging in a magnesium free solution. Notably, this induction occurred in a smaller fraction of spines in the neocortex in vivo (22%) than in hippocampal slices (95%). Once induced, the time course and mean long-term enlargement amplitudes were similar to those found in hippocampal slices. However, low-frequency (1–2 Hz) glutamate uncaging in the presence of magnesium caused spine shrinkage in a similar fraction (35%) of spines as in hippocampal slices, though spread to neighboring spines occurred less frequently than it did in hippocampal slices. Thus, the structural plasticity may occur similarly in the neocortex in vivo as in hippocampal slices, although it happened less frequently in our experimental conditions.

scholarly journals Amyloid Beta: Multiple Mechanisms of Toxicity and Only Some Protective Effects?

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Paul Carrillo-Mora ◽  
Rogelio Luna ◽  
Laura Colín-Barenque
Keyword(s):  
Amyloid Beta ◽  
Protective Effects ◽  
Protective Mechanisms ◽  
Experimental Conditions ◽  
Mechanisms Of Toxicity ◽  
Mitochondrial Alterations ◽  
Physiological Properties ◽  
Wide Range

Amyloid beta (Aβ) is a peptide of 39–43 amino acids found in large amounts and forming deposits in the brain tissue of patients with Alzheimer’s disease (AD). For this reason, it has been implicated in the pathophysiology of damage observed in this type of dementia. However, the role of Aβin the pathophysiology of AD is not yet precisely understood. Aβhas been experimentally shown to have a wide range of toxic mechanismsin vivoandin vitro, such as excitotoxicity, mitochondrial alterations, synaptic dysfunction, altered calcium homeostasis, oxidative stress, and so forth. In contrast, Aβhas also shown some interesting neuroprotective and physiological properties under certain experimental conditions, suggesting that both physiological and pathological roles of Aβmay depend on several factors. In this paper, we reviewed both toxic and protective mechanisms of Aβto further explore what their potential roles could be in the pathophysiology of AD. The complete understanding of such apparently opposed effects will also be an important guide for the therapeutic efforts coming in the future.

Corrigendum to “Ammonium chloride influences in vitro-neuronal network activity” [Experimental Neurology 235/1 (2008) 368–373]

2012 ◽  
Vol 236 (2) ◽  
pp. 240
Author(s):  
Clara-Sophie Schwarz ◽  
Stefano Ferrea ◽  
Kim Quasthoff ◽  
Janine Walter ◽  
Boris Görg ◽  
...  
Keyword(s):  
Ammonium Chloride ◽  
Neuronal Network ◽  
Network Activity ◽  
Experimental Neurology ◽  
Neuronal Network Activity
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