Detrimental Role of Corticotropin-Releasing Factor on the Decrease of CA1 Field Potential Induced by In Vitro Ischemia in Rat Hippocampal Slices

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.

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Ontogenetic differences in energy metabolism and inhibition of protein synthesis in hippocampal slices during in vitro ischemia and 24 h of recovery

Developmental Brain Research ◽

10.1016/0165-3806(95)00196-4 ◽

1996 ◽

Vol 91 (2) ◽

pp. 281-291 ◽

Cited By ~ 13

Author(s):

Richard Berger ◽

Bogdan Djuricic ◽

Arne Jensen ◽

Konstantin Alexander Hossmann ◽

Wulf Paschen

Keyword(s):

Protein Synthesis ◽

Energy Metabolism ◽

Hippocampal Slices ◽

In Vitro Ischemia ◽

Inhibition Of Protein Synthesis

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Enhanced Temporal Stability of Cholinergic Hippocampal Gamma Oscillations Following Respiratory Alkalosis In Vitro

Journal of Neurophysiology ◽

10.1152/jn.2001.85.5.2063 ◽

2001 ◽

Vol 85 (5) ◽

pp. 2063-2069 ◽

Cited By ~ 22

Author(s):

Kerstin Stenkamp ◽

J. Matias Palva ◽

Marylka Uusisaari ◽

Sebastian Schuchmann ◽

Dietmar Schmitz ◽

...

Keyword(s):

Time Constant ◽

Decay Time ◽

Oscillation Frequency ◽

Hippocampal Slices ◽

Temporal Stability ◽

Field Potential ◽

Gamma Oscillations ◽

Decay Time Constant ◽

The Mean

The decrease in brain CO2 partial pressure (pCO2) that takes place both during voluntary and during pathological hyperventilation is known to induce gross alterations in cortical functions that lead to subjective sensations and altered states of consciousness. The mechanisms that mediate the effects of the decrease in pCO2 at the neuronal network level are largely unexplored. In the present work, the modulation of gamma oscillations by hypocapnia was studied in rat hippocampal slices. Field potential oscillations were induced by the cholinergic agonist carbachol under an N-methyl-D-aspartate (NMDA)-receptor blockade and were recorded in the dendritic layer of the CA3 region with parallel measurements of changes in interstitial and intraneuronal pH (pHo and pHi, respectively). Hypocapnia from 5 to 1% CO2 led to a stable monophasic increase of 0.5 and 0.2 units in pHo and pHi, respectively. The mean oscillation frequency increased slightly but significantly from 32 to 34 Hz and the mean gamma-band amplitude (20 to 80 Hz) decreased by 20%. Hypocapnia induced a dramatic enhancement of the temporal stability of the oscillations, as was indicated by a two-fold increase in the exponential decay time constant fitted to the autocorrelogram. A rise in pHi evoked by the weak base trimethylamine (TriMA) was associated with a slight increase in oscillation frequency (37 to 39 Hz) and a decrease in amplitude (30%). Temporal stability, on the other hand, was decreased by TriMA, which suggests that its enhancement in 1% CO2 was related to the rise in pHo. In 1% CO2, the decay-time constant of the evoked monosynaptic pyramidal inhibitory postsynaptic current (IPSC) was unaltered but its amplitude was enhanced. This increase in IPSC amplitude seems to significantly contribute to the enhancement of temporal stability because the enhancement was almost fully reversed by a low concentration of bicuculline. These results suggest that changes in brain pCO2 can have a strong influence on the temporal modulation of gamma rhythms.

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Extrusion of Intracellular Calcium Ion After In Vitro Ischemia in the Rat Hippocampal CA1 Region

Journal of Neurophysiology ◽

10.1152/jn.2002.88.2.879 ◽

2002 ◽

Vol 88 (2) ◽

pp. 879-887 ◽

Cited By ~ 19

Author(s):

E. Tanaka ◽

H. Uchikado ◽

S. Niiyama ◽

K. Uematsu ◽

H. Higashi

Keyword(s):

Glial Cells ◽

Hippocampal Slices ◽

Negative Potential ◽

Acetoxymethyl Ester ◽

Rapid Reduction ◽

In Vitro Ischemia ◽

Ca1 Region ◽

Dc Potential ◽

Slow Negative Potential

Simultaneous recordings of intracellular Ca2+([Ca2+]i) signal and extracellular DC potential were obtained from the CA1 region in 1-[6-amino-2-(5-carboxy-2-oxazolyl)-5-benzofuranyloxy]-2-(2-amino-5-methylphenoxy)-ethane- N, N, N′, N′-tetraacetic acid penta-acetoxymethyl ester (Fura-2/AM)-loaded rat hippocampal slices. Superfusion with oxygen- and glucose-deprived medium (in vitro ischemia) for 5–6 min produced a rapid rise of the [Ca2+]i level in the stratum radiatum (rising phase of the [Ca2+]i signal), which occurred simultaneously with a rapid negative DC potential (rapid negative potential). When oxygen and glucose were reintroduced, the increased [Ca2+]i signal diminished rapidly (falling phase of the [Ca2+]i signal) during the generation of a slow negative DC potential (slow negative potential), which occurred within 1 min from the onset of the reintroduction. Thereafter, the [Ca2+]i signal partially and the slow negative potential completely returned to the preexposure level approximately 6 min after the reintroduction. The changes in [Ca2+]i signal during and after in vitro ischemia were very similar to the changes in the membrane potential of glial cells. The rising and falling phases of [Ca2+]i signal corresponded to the rapid depolarization and a depolarizing hump, respectively, in the repolarizing phase of glial cells. A prolonged application of in vitro ischemia or a reintroduction of either glucose or oxygen suppressed the falling phase after ischemic exposure. The application of ouabain (30 μM) generated both a rapid negative potential and a rapid elevation of [Ca2+]i, but no slow negative potential or rapid reduction in [Ca2+]i were observed. When oxygen and glucose were reintroduced to slices in the Na+-free or ouabain- or Ni2+-containing medium, the falling phase was suppressed. The falling phase was significantly accelerated in Ca2+- and Mg2+-free with EGTA-containing medium. In contrast, the falling phase was significantly slower in the Ca2+-free with high Mg2+- and EGTA-containing medium. The falling phase of the [Ca2+]isignal after ischemic exposure is thus considered to be primarily dependent on the reactivation of Na+, K+-ATPases, while the extrusion of cytosolic Ca2+ via the forward-mode operation of Na+/Ca2+ exchangers in glial cells is thought to be directly involved in the rapid reduction of [Ca2+]i after ischemic exposure.

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Endotoxin preconditioning protects neurones from in vitro ischemia: Role of endogenous IL-1β and TNF-α

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2005.12.006 ◽

2006 ◽

Vol 173 (1-2) ◽

pp. 108-116 ◽

Cited By ~ 27

Author(s):

Isabel Lastres-Becker ◽

Tam Cartmell ◽

Francisco Molina-Holgado

Keyword(s):

In Vitro Ischemia ◽

Tnf Α

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Origin of intracellular Ca2+ elevation induced by in vitro ischemia-like condition in hippocampal slices

Brain Research ◽

10.1016/0006-8993(93)91700-3 ◽

1993 ◽

Vol 601 (1-2) ◽

pp. 103-110 ◽

Cited By ~ 93

Author(s):

Akira Mitani ◽

Hisato Yanase ◽

Kimiko Sakai ◽

Youseke Wake ◽

Kiyoshi Kataoka

Keyword(s):

Hippocampal Slices ◽

In Vitro Ischemia

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Conditional Upregulation of KCC2 selectively enhances neuronal inhibition during seizures

10.1101/253831 ◽

2018 ◽

Cited By ~ 1

Author(s):

CS Goulton ◽

M Watanabe ◽

DL Cheung ◽

KW Wang ◽

T Oba ◽

...

Keyword(s):

Status Epilepticus ◽

Transgenic Mouse ◽

Brain Function ◽

Neuronal Excitability ◽

Hippocampal Slices ◽

Transport Function ◽

Neuronal Inhibition ◽

Proof Of Principle

Abstract/SummaryEfficacious neuronal inhibition is sustained by the neuronal K+Cl- co-transporter KCC2, and loss of KCC2 function through injury or mutation is associated with altered GABAergic signalling and neuronal seizures. Here we report a transgenic mouse with conditional KCC2 overexpression that results in increased membrane transport function. Increased KCC2 has little impact on behavioural and in vitro assays of neuronal excitability and GABAA receptor responses under resting conditions. In contrast, increased KCC2 imparts resistance to seizure-like neuronal activity in hippocampal slices and prevents the progression of mice into behavioural status epilepticus following multiple kainic acid doses. Our results demonstrate a transgenic mouse to facilitate investigations into the role of KCC2 in brain function, and provide a proof of principle that targeting KCC2 may be an effective way to selectively enhance neuronal inhibition to mitigate against diseases that involve an imbalance between excitation and inhibition.

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Role of Group I Metabotropic Glutamate Receptors in the Patterning of Epileptiform Activities In Vitro

Journal of Neurophysiology ◽

10.1152/jn.1997.78.1.539 ◽

1997 ◽

Vol 78 (1) ◽

pp. 539-544 ◽

Cited By ~ 83

Author(s):

Lisa R. Merlin ◽

Robert K. S. Wong

Keyword(s):

Guinea Pig ◽

Glutamate Receptors ◽

Metabotropic Glutamate Receptors ◽

Hippocampal Slices ◽

Metabotropic Glutamate ◽

Group I ◽

Group I Mglurs ◽

Synaptic Responses

Merlin, Lisa R. and Robert K. S. Wong. Role of group I metabotropic glutamate receptors in the patterning of epileptiform activities in vitro. J. Neurophysiol. 78: 539–544, 1997. In guinea pig hippocampal slices, picrotoxin elicited spontaneous epileptiform bursts 300–550 ms in duration. Additional application of ( R,S)-3,5-dihydroxyphenylglycine or ( S)-3-hydroxyphenylglycine, agonists specific for group I metabotropic glutamate receptors(mGluRs), or (1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylicacid, a broad-spectrum mGluR agonist, converted picrotoxin-induced interictal bursts into prolonged discharges measured on the order of seconds. The prolonged discharges induced by selective group I mGluR agonist continued to be produced for hours after agonist removal. The antagonists ( S)-4-carboxyphenylglycine and (+)-α-methyl-4-carboxyphenylglycine had no effect on the duration of picrotoxin-induced interictal bursts. However, after agonist exposure, the persistent prolonged discharges occurring in the absence of agonist were reversibly suppressed by the antagonists, suggesting that the activity is maintained via endogenous activation of group I mGluRs by synaptically released glutamate. Our results suggest that, under some conditions, activation of group I mGluRs produces long-lasting enhancement of synaptic responses, mediated at least in part by autopotentiation of the group I mGluR response itself, which may result in the production of seizure discharges and contribute to epileptogenesis.

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