scholarly journals Increased molecular plasticity along the septotemporal axis of the hippocampus is associated with network functioning

2019 ◽  
Author(s):  
Evangelos Sotiriou ◽  
Fevronia Angelatou ◽  
Costas Papatheodoropoulos
Keyword(s):  
Hippocampal Slices ◽  
Longitudinal Axis ◽  
Ventral Hippocampus ◽  
Network Activity ◽  
Molecular Organization ◽  
Dynamic Tuning ◽  
Sharp Waves ◽  
Neuronal Network Dynamics ◽  
Molecular Plasticity

AbstractMolecular plasticity crucially supports adaptive cellular and network functioning in the brain. Variations in molecular plasticity may yield important differences in neuronal network dynamics between discrete brain subregions. In the present study we show that the gradual development of sharp waves (SPWs), a spontaneous network activity that is organized under normalin vitroconditions in the CA1 field of ventral but not dorsal hippocampal slices, is associated with region selective molecular reorganization. In particular, increased levels of mRNAs for specific GABAAreceptor subunits (α1, β2, γ2) occurred in ventral hippocampal CA1 field during the development of SPWs. These mRNA changes were followed by a clear increase in GABAAreceptor number in ventral hippocampus, as shown by [3H]muscimol binding. An increase in mRNAs was also observed in dorsal slices for α2 and α5 subunits, not followed by quantitative GABAAreceptor changes. Furthermore, full development of SPWs in the CA1 field (at 3 hours of slice maintenancein vitro) was followed by increased expression of immediate early genes c-fos and zif-268 in ventral hippocampal slices (measured at 5 hoursin vitro). No change in c-fos and zif-268 levels is observed in the CA1 field of dorsal slices, which do not develop spontaneous activity. These results suggest that generation of SPWs could trigger specific molecular reorganization in the VH that may be related to the functional roles of SPWs. Correspondingly, the revealed increased potentiality of the ventral hippocampus for molecular reorganization may provide a clue to mechanisms that underlie the regulated emergence of SPWs along the longitudinal axis of the hippocampus. Furthermore, the present evidence suggests that dynamic tuning between spontaneous neuronal activity and molecular organization may importantly contribute to the functional segregation/heterogeneity seen along the hippocampus.

scholarly journals An In Vitro Model of Hippocampal Sharp Waves: Regional Initiation and Intracellular Correlates

2005 ◽  
Vol 94 (1) ◽  
pp. 741-753 ◽  
Author(s):  
Chiping Wu ◽  
Marjan Nassiri Asl ◽  
Jesse Gillis ◽  
Frances K. Skinner ◽  
Liang Zhang
Keyword(s):  
Dentate Gyrus ◽  
Large Amplitude ◽  
Pyramidal Neurons ◽  
Slow Wave Sleep ◽  
Hippocampal Slices ◽  
Field Potentials ◽  
Sharp Wave ◽  
Sharp Waves ◽  
Hippocampal Circuitry

During slow wave sleep and consummatory behaviors, electroencephalographic recordings from the rodent hippocampus reveal large amplitude potentials called sharp waves. The sharp waves originate from the CA3 circuitry and their generation is correlated with coherent discharges of CA3 pyramidal neurons and dependent on activities mediated by AMPA glutamate receptors. To model sharp waves in a relatively large hippocampal circuitry in vitro, we developed thick (1 mm) mouse hippocampal slices by separating the dentate gyrus from the CA2/CA1 areas while keeping the functional dentate gyrus-CA3-CA1 connections. We found that large amplitude (0.3–3 mV) sharp wave-like field potentials occurred spontaneously in the thick slices without extra ionic or pharmacological manipulation and they resemble closely electroencephalographic sharp waves with respect to waveform, regional initiation, pharmacological manipulations, and intracellular correlates. Through measuring tissue O2, K+, and synaptic and single cell activities, we verified that the sharp wave-like potentials are not a consequence of anoxia, nonspecific elevation of extracellular K+ and dissection-related tissue damage. Our data suggest that a subtle but crucial increase in the CA3 glutamatergic activity effectively recruits a population of neurons thus responsible for the generation of the sharp wave-like spontaneous field potentials in isolated hippocampal circuitry.

scholarly journals In vivo ketogenic diet treatment attenuates pathologic sharp waves and high frequency oscillations in in vitro hippocampal slices from epileptic Kv1.1α knockout mice

Epilepsia ◽  
2014 ◽  
Vol 55 (5) ◽  
pp. e44-e49 ◽  
Author(s):  
Timothy A. Simeone ◽  
Kaeli K. Samson ◽  
Stephanie A. Matthews ◽  
Kristina A. Simeone
Keyword(s):  
Ketogenic Diet ◽  
Knockout Mice ◽  
High Frequency ◽  
Hippocampal Slices ◽  
Sharp Waves ◽  
High Frequency Oscillations ◽  
Diet Treatment

scholarly journals Loss of the Kv1.1 potassium channel promotes pathologic sharp waves and high frequency oscillations in in vitro hippocampal slices

2013 ◽  
Vol 54 ◽  
pp. 68-81 ◽  
Author(s):  
Timothy A. Simeone ◽  
Kristina A. Simeone ◽  
Kaeli K. Samson ◽  
Do Young Kim ◽  
Jong M. Rho
Keyword(s):  
Potassium Channel ◽  
High Frequency ◽  
Hippocampal Slices ◽  
Sharp Waves ◽  
High Frequency Oscillations

Desynchronization of Glutamate Release Prolongs Synchronous CA3 Network Activity

2007 ◽  
Vol 97 (5) ◽  
pp. 3812-3818 ◽  
Author(s):  
Jethro Jones ◽  
Elizabeth A. Stubblefield ◽  
Timothy A. Benke ◽  
Kevin J. Staley
Keyword(s):  
Glutamate Release ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Network Activity ◽  
Neural Population ◽  
Axon Terminals ◽  
Rate Of Spread ◽  
Hippocampal Ca3 ◽  
Recurrent Collateral

Periodic bursts of activity in the disinhibited in vitro hippocampal CA3 network spread through the neural population by the glutamatergic recurrent collateral axons that link CA3 pyramidal cells. It was previously proposed that these bursts of activity are terminated by exhaustion of releasable glutamate at the recurrent collateral synapses so that the next periodic burst of network activity cannot occur until the supply of glutamate has been replenished. As a test of this hypothesis, the rate of glutamate release at CA3 axon terminals was reduced by substitution of extracellular Ca2+ with Sr2+. Reduction of the rate of glutamate release reduces the rate of depletion and should thereby prolong bursts. Here we demonstrate that Sr2+ substitution prolongs spontaneous bursts in the disinhibited adult CA3 hippocampal slices to 37.2 ± 7.6 (SE) times the duration in control conditions. Sr2+ also decreased the probability of burst initiation and the rate of burst onset, consistent with reduced synchrony of glutamate release and a consequent reduced rate of spread of excitation through the slice. These findings support the supply of releasable glutamate as an important determinant of the probability and duration of synchronous CA3 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.

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.

Aluminum Suppresses Effect of Nicotine on Gamma Oscillations (20-40 Hz) in Mouse Hippocampal Slices

2018 ◽  
Vol 17 (6) ◽  
pp. 404-411 ◽  
Author(s):  
Syeda Mehpara Farhat ◽  
Touqeer Ahmed
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Cholinergic System ◽  
Acetylcholine Receptors ◽  
Peak Power ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Gamma Oscillations ◽  
Gamma Oscillation ◽  
Facilitatory Effect

Background: Aluminum (Al) causes neurodegeneration and its toxic effects on cholinergic system in the brain is well documented. However, it is unknown whether and how Al changes oscillation patterns, driven by the cholinergic system, in the hippocampus. Objective: We studied acute effects of Al on nicotinic acetylcholine receptors (nAChRs)-mediated modulation of persistent gamma oscillations in the hippocampus. Method: The field potential recording was done in CA3 area of acute hippocampal slices. Results: Carbachol-induced gamma oscillation peak power increased (1.32±0.09mV2/Hz, P<0.01) in control conditions (without Al) by application of 10µM nicotine as compared to baseline value normalized to 1. This nicotine-induced facilitation of gamma oscillation peak power was found to depend on non-α7 nAChRs. In slices with Al pre-incubation for three to four hours, gamma oscillation peak power was reduced (5.4±1.8mV2/Hz, P<0.05) and facilitatory effect of nicotine on gamma oscillation peak power was blocked as compared to the control (18.06±2.1mV2/Hz) or one hour Al pre-incubated slices (11.3±2.5mV2/Hz). Intriguingly wash-out, after three to four hours of Al incubation, failed to restore baseline oscillation power and its facilitation by nicotine as no difference was observed in gamma oscillation peak power between Al wash-out slices (3.4±1.1mV2/Hz) and slices without washout (3.6±0.9mV2/Hz). Conclusion: This study shows that at cellular level, exposure of hippocampal tissue to Al compromised nAChR-mediated facilitation of cholinergic hippocampal gamma oscillations. Longer in vitro Al exposure caused permanent changes in hippocampal oscillogenic circuitry and changed its sensitivity to nAChR-modulation. This study will help to understand the possible mechanism of cognitive decline induced by Al.

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.

scholarly journals Structural and functional analysis of LIM domain-dependent recruitment of paxillin to αvβ3 integrin-positive focal adhesions

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Marta Ripamonti ◽  
Nicolas Liaudet ◽  
Latifeh Azizi ◽  
Daniel Bouvard ◽  
Vesa P. Hytönen ◽  
...  
Keyword(s):  
Focal Adhesions ◽  
Bimolecular Fluorescence Complementation ◽  
Molecular Organization ◽  
Structural Function ◽  
Αvβ3 Integrin ◽  
Lim Domain ◽  
Dissociation Kinetics ◽  
Mechanical Coupling ◽  
Β3 Integrin

AbstractThe LIM domain-dependent localization of the adapter protein paxillin to β3 integrin-positive focal adhesions (FAs) is not mechanistically understood. Here, by combining molecular biology, photoactivation and FA-isolation experiments, we demonstrate specific contributions of each LIM domain of paxillin and reveal multiple paxillin interactions in adhesion-complexes. Mutation of β3 integrin at a putative paxillin binding site (β3VE/YA) leads to rapidly inward-sliding FAs, correlating with actin retrograde flow and enhanced paxillin dissociation kinetics. Induced mechanical coupling of paxillin to β3VE/YA integrin arrests the FA-sliding, thereby disclosing an essential structural function of paxillin for the maturation of β3 integrin/talin clusters. Moreover, bimolecular fluorescence complementation unveils the spatial orientation of the paxillin LIM-array, juxtaposing the positive LIM4 to the plasma membrane and the β3 integrin-tail, while in vitro binding assays point to LIM1 and/or LIM2 interaction with talin-head domain. These data provide structural insights into the molecular organization of β3 integrin-FAs.

scholarly journals Molecular organization of mammalian meiotic chromosome axis revealed by expansion STORM microscopy

2019 ◽  
Vol 116 (37) ◽  
pp. 18423-18428 ◽  
Author(s):  
Huizhong Xu ◽  
Zhisong Tong ◽  
Qing Ye ◽  
Tengqian Sun ◽  
Zhenmin Hong ◽  
...  
Keyword(s):  
Meiotic Chromosome ◽  
Molecular Organization ◽  
Homologous Chromosomes ◽  
Meiotic Chromosomes ◽  
C Terminus ◽  
Stochastic Optical Reconstruction Microscopy ◽  
Optical Reconstruction ◽  
20 Nm ◽  
Chromosome Axis

During prophase I of meiosis, chromosomes become organized as loop arrays around the proteinaceous chromosome axis. As homologous chromosomes physically pair and recombine, the chromosome axis is integrated into the tripartite synaptonemal complex (SC) as this structure’s lateral elements (LEs). While the components of the mammalian chromosome axis/LE—including meiosis-specific cohesin complexes, the axial element proteins SYCP3 and SYCP2, and the HORMA domain proteins HORMAD1 and HORMAD2—are known, the molecular organization of these components within the axis is poorly understood. Here, using expansion microscopy coupled with 2-color stochastic optical reconstruction microscopy (STORM) imaging (ExSTORM), we address these issues in mouse spermatocytes at a resolution of 10 to 20 nm. Our data show that SYCP3 and the SYCP2 C terminus, which are known to form filaments in vitro, form a compact core around which cohesin complexes, HORMADs, and the N terminus of SYCP2 are arrayed. Overall, our study provides a detailed structural view of the meiotic chromosome axis, a key organizational and regulatory component of meiotic chromosomes.

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