scholarly journals Silencing-Induced Metaplasticity in Hippocampal Cultured Neurons

2008 ◽  
Vol 100 (2) ◽  
pp. 690-697 ◽  
Author(s):  
Irina V. Sokolova ◽  
Istvan Mody
Keyword(s):  
Hippocampal Neurons ◽  
Channel Blocker ◽  
Recovery Period ◽  
Long Term Potentiation ◽  
Homeostatic Plasticity ◽  
Membrane Properties ◽  
Postsynaptic Currents ◽  
Short Period ◽  
Spiking Activity

Silencing-induced homeostatic plasticity is usually expressed as a change in the amplitude or the frequency of miniature postsynaptic currents. Here we report that, prolonged (∼24 h) silencing of mature (20–22 days in vitro) cultured hippocampal neurons using the voltage-gated sodium channel blocker tetrodotoxin (TTX) produced no effects on the amplitude or frequency of the miniature excitatory postsynaptic currents (mEPSCs). However, the silencing changed the intrinsic membrane properties of the neurons, resulting in an increased excitability and rate of action potentials firing upon TTX washout. Allowing neurons to recover in TTX-free recording solution for a short period of time after the silencing resulted in potentiation of mEPSC amplitudes. This form of activity-dependent potentiation is different from classical long-term potentiation, as similar potentiation was not seen in nonsilenced neurons treated with bicuculline to raise their spiking activity to the same level displayed by the silenced neurons during TTX washout. Also, the potentiation of mEPSC amplitudes after the recovery period was not affected by the N-methyl-d-aspartate receptor blocker d-2-amino-5-phosponopentanoic acid or by the calcium/calmodulin-dependent kinase II (CaMKII) inhibitor KN-62 but was abolished by the L-type calcium channel blocker nifedipine. We thus conclude that the potentiation of mEPSC amplitudes following brief recovery of spiking activity in chronically silenced neurons represents a novel form of metaplasticity that differs from the conventional models of homeostatic synaptic plasticity.

scholarly journals Homeostatic plasticity and external input shape neural network dynamics

2018 ◽  
Author(s):  
Johannes Zierenberg ◽  
Jens Wilting ◽  
Viola Priesemann
Keyword(s):  
Neural Network ◽  
Brain Area ◽  
External Input ◽  
Homeostatic Plasticity ◽  
Dynamic State ◽  
Network Topologies ◽  
Neural Network Dynamics ◽  
Spiking Activity

In vitro and in vivo spiking activity clearly differ. Whereas networks in vitro develop strong bursts separated by periods of very little spiking activity, in vivo cortical networks show continuous activity. This is puzzling considering that both networks presumably share similar single-neuron dynamics and plasticity rules. We propose that the defining difference between in vitro and in vivo dynamics is the strength of external input. In vitro, networks are virtually isolated, whereas in vivo every brain area receives continuous input. We analyze a model of spiking neurons in which the input strength, mediated by spike rate homeostasis, determines the characteristics of the dynamical state. In more detail, our analytical and numerical results on various network topologies show consistently that under increasing input, homeostatic plasticity generates distinct dynamic states, from bursting, to close-to-critical, reverberating and irregular states. This implies that the dynamic state of a neural network is not fixed but can readily adapt to the input strengths. Indeed, our results match experimental spike recordings in vitro and in vivo: the in vitro bursting behavior is consistent with a state generated by very low network input (< 0.1%), whereas in vivo activity suggests that on the order of 1% recorded spikes are input-driven, resulting in reverberating dynamics. Importantly, this predicts that one can abolish the ubiquitous bursts of in vitro preparations, and instead impose dynamics comparable to in vivo activity by exposing the system to weak long-term stimulation, thereby opening new paths to establish an in vivo-like assay in vitro for basic as well as neurological studies.

Anoxia-induced LTP of isolated NMDA receptor-mediated synaptic responses

1993 ◽  
Vol 69 (5) ◽  
pp. 1774-1778 ◽  
Author(s):  
V. Crepel ◽  
C. Hammond ◽  
K. Krnjevic ◽  
P. Chinestra ◽  
Y. Ben-Ari
Keyword(s):  
Nmda Receptor ◽  
Neuronal Death ◽  
Hippocampal Neurons ◽  
Input Resistance ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Bath Application ◽  
Synaptic Responses

1. The effects of an anoxic-aglycemic episode (1-3 min) on the pharmacologically isolated N-methyl-D-aspartate (NMDA)-mediated responses were examined in CA1 pyramidal hippocampal neurons in vitro. 2. An anoxic-aglycemic episode induced a long term potentiation (LTP) of the NMDA receptor-mediated field excitatory post-synoptic potentials (EPSPs). This LTP, referred to as anoxic LTP, was observed in the presence of 1) a normal Mg2+ concentration [+40.1 +/- 5% (mean +/- SE)], 2) a low Mg2+ concentration (+52.2 +/- 10%), or 3) a Mg2+ free (+49 +/- 11%), 1 h after anoxia. 3. Bath application of D-2-amino-5-phosphonovaleric acid (D-APV, 20 microM, 15-21 min) before, during, and after the anoxic-aglycemic episode, which transiently blocked the synaptic NMDA receptor mediated response, prevented the induction of anoxic LTP. 4. The intracellularly recorded NMDA receptor-mediated EPSP was also persistently potentiated by anoxia-aglycemia (+47 +/- 4%). This potentiation was not associated with changes in membrane potential or input resistance. 5. These findings provide the first evidence that an anoxic-aglycemic episode induces an LTP of NMDA receptor-mediated responses. This potentiation may participate in the cascade of events that lead to delayed neuronal death.

Differential effects of protein kinase inhibitors on pre-established long-term potentiation in rat hippocampal neurons in vitro

1991 ◽  
Vol 121 (1-2) ◽  
pp. 259-262 ◽  
Author(s):  
Henry Matthies ◽  
Thomas Behnisch ◽  
Hiroshi Kase ◽  
Hansjürgen Matthies ◽  
Klaus G. Reymann
Keyword(s):  
Protein Kinase ◽  
Hippocampal Neurons ◽  
Kinase Inhibitors ◽  
Long Term Potentiation ◽  
Protein Kinase Inhibitors ◽  
Differential Effects ◽  
Term Potentiation

scholarly journals Direct Actions of Carbenoxolone on Synaptic Transmission and Neuronal Membrane Properties

2009 ◽  
Vol 102 (2) ◽  
pp. 974-978 ◽  
Author(s):  
Kenneth R. Tovar ◽  
Brady J. Maher ◽  
Gary L. Westbrook
Keyword(s):  
Action Potential ◽  
Synaptic Transmission ◽  
Gap Junctions ◽  
Hippocampal Neurons ◽  
Electrical Coupling ◽  
Network Activity ◽  
Membrane Properties ◽  
Neuronal Membrane ◽  
Postsynaptic Currents ◽  
Gap Junctional

The increased appreciation of electrical coupling between neurons has led to many studies examining the role of gap junctions in synaptic and network activity. Although the gap junctional blocker carbenoxolone (CBX) is effective in reducing electrical coupling, it may have other actions as well. To study the non–gap junctional effects of CBX on synaptic transmission, we recorded from mouse hippocampal neurons cultured on glial micro-islands. This recording configuration allowed us to stimulate and record excitatory postsynaptic currents (EPSCs) or inhibitory postsynaptic currents (IPSCs) in the same neuron or pairs of neurons. CBX irreversibly reduced evoked α-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) receptor–mediated EPSCs. Consistent with a presynaptic site of action, CBX had no effect on glutamate-evoked whole cell currents and increased the paired-pulse ratio of AMPA and N-methyl-d-aspartate (NMDA) receptor–mediated EPSCs. CBX also reversibly reduced GABAA receptor–mediated IPSCs, increased the action potential width, and reduced the action potential firing rate. Our results indicate CBX broadly affects several neuronal membrane conductances independent of its effects on gap junctions. Thus effects of carbenoxolone on network activity cannot be interpreted as resulting from specific block of gap junctions.

Unilateral Dopamine Denervation Blocks Corticostriatal LTP

1999 ◽  
Vol 82 (6) ◽  
pp. 3575-3579 ◽  
Author(s):  
Diego Centonze ◽  
Paolo Gubellini ◽  
Barbara Picconi ◽  
Paolo Calabresi ◽  
Patrizia Giacomini ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Long Term Potentiation ◽  
Membrane Properties ◽  
High Frequency Stimulation ◽  
Cortex Lesion ◽  
Electrophysiological Recordings ◽  
Motor Information ◽  
6 Hydroxydopamine

The nigrostriatal dopaminergic projection is crucial for the striatal processing of motor information received from the cortex. Lesion of this pathway in rats causes locomotor alterations that resemble some of the symptoms of Parkinson's disease and significantly alters the excitatory transmission in the striatum. We performed in vitro electrophysiological recordings to study the effects of unilateral striatal dopamine (DA) denervation obtained by omolateral nigral injection of 6-hydroxydopamine (6-OHDA) in the formation of corticostriatal long-term potentiation (LTP). Unilateral nigral lesion did not affect the intrinsic membrane properties of striatal spiny neurons. In fact, these cells showed similar pattern of firing discharge and current-voltage relationship in denervated striata and in naive controlateral striata. Moreover, excitatory postsynaptic potentials (EPSPs) evoked by stimulating corticostriatal fibers and recorded from DA-denervated slices showed a pharmacology similar to that observed in slices obtained from controlateral intact striata. Conversely, in magnesium-free medium, high-frequency stimulation (HFS) of corticostriatal fibers produced LTP in slices from nondenervated striata but not in slices from 6-OHDA–denervated rats. After denervation, in fact, no significant changes in the amplitude of extra- and intracellular synaptic potentials were recorded after the conditioning HFS. The absence of corticostriatal LTP in DA-denervated striata might represent the cellular substrate for some of the movement disorders observed in Parkinson's disease.

A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons

1980 ◽  
Vol 43 (2) ◽  
pp. 409-419 ◽  
Author(s):  
J. R. Hotson ◽  
D. A. Prince
Keyword(s):  
Cortical Neurons ◽  
Hippocampal Neurons ◽  
Channel Blocker ◽  
Repetitive Firing ◽  
Na Channel ◽  
Molluscan Neurons ◽  
Potential Oscillations ◽  
Ca1 Neurons ◽  
K Current

1. A long-lasting afterhyperpolarization (AHP) follows current-induced repetitive firing in hippocampal CA1 neurons studied in vitro. A 10-25% increase in membrane slope conductance occurs during the AHP, suggesting that it may be mediated by an increased conductance to either K+ or Cl-. 2. Intracellular Cl- iontophoresis does not alter the AHP but does attenuate the IPSP. In contrast Ba2+, a cation that can decrease K+ conductance, eliminates the AHP but not the IPSP. These findings suggest the AHP is produced by a long-lasting increased conductance to K+, and is distinct from the IPSP. 3. Mn2+, a Ca2+-channel blocker, eliminates the AHP. In comparison, the AHP persists in the presence of the Na+-channel blocker, tetrodotoxin (TTX), and appears to be temporally associated with TTX-resistant "Ca2+ spikes." It is concluded that AHP is probably activated by Ca2+ influx. 4. These observations indicate that the AHP may be produced by a Ca2+ activated K+ current. A balance between cellular depolarization produced by Ca2+ entry and repolarization generated by a Ca2+-activated K+ current appears to operate to control excitability in some mammalian cortical neurons as it does in molluscan neurons. Disruption of this balance by Ba2+ produces spontaneous membrane-potential oscillations and recurrent burst firing in hippocampal neurons. Increases in the magnitude and duration of Ca2+ depolarization and/or decreases in the Ca2+-activated, K+-mediated repolarization may be mechanisms that lead to spontaneous, epileptiform bursting in mammalian cortical neurons.

scholarly journals 2-Deoxy-d-glucose reduces epileptiform activity by presynaptic mechanisms

2019 ◽  
Vol 121 (4) ◽  
pp. 1092-1101 ◽  
Author(s):  
Yu-Zhen Pan ◽  
Thomas P. Sutula ◽  
Paul A. Rutecki
Keyword(s):  
Pyramidal Neurons ◽  
Epileptiform Activity ◽  
Network Activity ◽  
Membrane Properties ◽  
Extracellular Potassium ◽  
Acute Effects ◽  
Postsynaptic Currents ◽  
Neuronal Network Activity ◽  
Presynaptic Mechanisms

2-Deoxy-d-glucose (2DG), a glucose analog that inhibits glycolysis, has acute and chronic antiepileptic effects. We evaluated 2DG’s acute effects on synaptic and membrane properties of CA3 pyramidal neurons in vitro. 2DG (10 mM) had no effects on spontaneously occurring postsynaptic currents (PSCs) in 3.5 mM extracellular potassium concentration ([K+]o). In 7.5 mM [K+]o, 2DG significantly reduced the frequency of epileptiform bursting and the charge carried by postsynaptic currents (PSCs) with a greater effect on inward excitatory compared with outward inhibitory charge (71% vs. 40%). In 7.5 mM [K+]o and bicuculline, 2DG reduced significantly the excitatory charge by 67% and decreased the frequency but not amplitude of excitatory PSCs between bursts. In 7.5 mM [K+]o, 2DG reduced pharmacologically isolated inhibitory PSC frequency without a change in amplitude. The frequency but not amplitude of inward miniature PSCs was reduced when 2DG was applied in 7.5 mM [K+]o before bath application of TTX, but there was no effect when 2DG was applied after TTX, indicating a use-dependent uptake of 2DG was required for its actions at a presynaptic locus. 2DG did not alter membrane properties of CA3 neurons except for reducing the slow afterhyperpolarization in 3.5 but not 7.5 mM [K+]o. The reduction in frequency of spontaneous and inward miniature PSCs in elevated [K+]o indicates a presynaptic mechanism of action. 2DG effects required use-dependent uptake and suggest an important role for glycolysis in neuronal metabolism and energetics in states of high neural activity as occur during abnormal network synchronization and seizures. NEW & NOTEWORTHY 2-Deoxy-d-glucose (2DG) is a glycolytic inhibitor and suppresses epileptiform activity acutely and has chronic antiepileptic effects. The mechanisms of the acute effects are not well delineated. In this study, we show 2DG suppressed abnormal network epileptiform activity without effecting normal synaptic network activity or membrane properties. The effects appear to be use dependent and have a presynaptic locus of action. Inhibition of glycolysis is a novel presynaptic mechanism to limit abnormal neuronal network activity and seizures.

2-Deoxyglucose–Induced Long-Term Potentiation of Monosynaptic IPSPs in CA1 Hippocampal Neurons

2000 ◽  
Vol 83 (2) ◽  
pp. 879-887 ◽  
Author(s):  
Krešimir Krnjević ◽  
Yong-Tao Zhao
Keyword(s):  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Inhibitory Synapses ◽  
Current Clamp ◽  
Glutamate Antagonists ◽  
Postsynaptic Potentials ◽  
Postsynaptic Currents ◽  
Inhibitory Postsynaptic Potentials ◽  
Term Potentiation

In previous experiments on excitatory synaptic transmission in CA1, temporary (10–20 min) replacement of glucose with 10 mM 2-deoxyglucose (2-DG) consistently caused a marked and very sustained potentiation (2-DG LTP). To find out whether 2-DG has a similar effect on inhibitory synapses, we recorded pharmacologically isolated mononosynaptic inhibitory postsynaptic potentials (IPSPs; under current clamp) and inhibitory postsynaptic currents (IPSCs; under voltage clamp); 2-DG was applied both in the presence and the absence of antagonists of N-methyl-d-aspartate (NMDA). In spite of sharply varied results (some neurons showing large potentiation, lasting for >1 h, and many little or none), overall there was a significant and similar potentiation of IPSP conductance, both for the early (at ≈30 ms) and later (at ≈140 ms) components of IPSPs or IPSCs: by 35.1 ± 10.25% (mean ± SE; for n = 24, P = 0.0023) and 36.5 ± 16.3% (for n = 19, P = 0.038), respectively. The similar potentiation of the early and late IPSP points to a presynaptic mechanism of LTP. Overall, the LTP was statistically significant only when 2-DG was applied in the absence of glutamate antagonists. Tetanic stimulations (in presence or absence of glutamate antagonists) only depressed IPSPs (by half). In conclusion, although smaller and more variable, 2-DG–induced LTP of inhibitory synapses appears to be broadly similar to the 2-DG–induced LTP of excitatory postsynaptic potentials previously observed in CA1.

scholarly journals Calcium-dependent activator protein for secretion 2 (CAPS2) promotes BDNF secretion and is critical for the development of GABAergic interneuron network

2010 ◽  
Vol 108 (1) ◽  
pp. 373-378 ◽  
Author(s):  
Yo Shinoda ◽  
Tetsushi Sadakata ◽  
Kazuhito Nakao ◽  
Ritsuko Katoh-Semba ◽  
Emi Kinameri ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Late Phase ◽  
Biological Significance ◽  
Long Term Potentiation ◽  
Inhibitory Neurons ◽  
Gabaergic Interneuron ◽  
Dense Core Vesicle ◽  
Calcium Dependent ◽  
Postsynaptic Currents ◽  
Activator Protein

Calcium-dependent activator protein for secretion 2 (CAPS2) is a dense-core vesicle-associated protein that is involved in the secretion of BDNF. BDNF has a pivotal role in neuronal survival and development, including the development of inhibitory neurons and their circuits. However, how CAPS2 affects BDNF secretion and its biological significance in inhibitory neurons are largely unknown. Here we reveal the role of CAPS2 in the regulated secretion of BDNF and show the effect of CAPS2 on the development of hippocampal GABAergic systems. We show that CAPS2 is colocalized with BDNF, both synaptically and extrasynaptically in axons of hippocampal neurons. Overexpression of exogenous CAPS2 in hippocampal neurons of CAPS2-KO mice enhanced depolarization-induced BDNF exocytosis events in terms of kinetics, frequency, and amplitude. We also show that in the CAPS2-KO hippocampus, BDNF secretion is reduced, and GABAergic systems are impaired, including a decreased number of GABAergic neurons and their synapses, a decreased number of synaptic vesicles in inhibitory synapses, and a reduced frequency and amplitude of miniature inhibitory postsynaptic currents. Conversely, excitatory neurons in the CAPS2-KO hippocampus were largely unaffected with respect to field excitatory postsynaptic potentials, miniature excitatory postsynaptic currents, and synapse number and morphology. Moreover, CAPS2-KO mice exhibited several GABA system-associated deficits, including reduced late-phase long-term potentiation at CA3–CA1 synapses, decreased hippocampal theta oscillation frequency, and increased anxiety-like behavior. Collectively, these results suggest that CAPS2 promotes activity-dependent BDNF secretion during the postnatal period that is critical for the development of hippocampal GABAergic networks.

Temporal Regulation of the Expression Locus of Homeostatic Plasticity

2006 ◽  
Vol 96 (4) ◽  
pp. 2127-2133 ◽  
Author(s):  
Corette J. Wierenga ◽  
Michael F. Walsh ◽  
Gina G. Turrigiano
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Homeostatic Plasticity ◽  
Excitatory Synapses ◽  
Postsynaptic Response ◽  
Network Function ◽  
Cortical Cultures ◽  
Mepsc Frequency ◽  
Visual Cortical

Homeostatic plasticity of excitatory synapses plays an important role in stabilizing neuronal activity, but the mechanism of this form of plasticity is incompletely understood. In particular, whether the locus of expression is presynaptic or postsynaptic has been controversial. Here we show that the expression locus depends on the time neurons have spent in vitro. In visual cortical cultures ≤14 days in vitro (DIV), 2 days of TTX treatment induced an increase in miniature excitatory postsynaptic current (mEPSC) amplitude onto pyramidal neurons, without affecting mEPSC frequency. However, in cultures ≥18 DIV, the same TTX treatment induced a large increase in mEPSC frequency, whereas the amplitude effect was reduced. The increased mEPSC frequency was associated with an increased density of excitatory synapses and increased presynaptic vesicle release in response to electrical stimulation. This indicates a shift from a predominantly postsynaptic response to TTX in ≤14 DIV cultures, to a coordinated pre- and postsynaptic response in ≥18 DIV cultures. This shift was not specific for cortical cultures because a similar shift was observed in cultured hippocampal neurons. Culturing neurons from older animals showed that the timing of the switch depends on the time the neurons have spent in vitro, rather than their postnatal age. This temporal switch in expression locus can largely reconcile the contradictory literature on the expression locus of homeostatic excitatory synaptic plasticity in central neurons. Furthermore, our results raise the intriguing possibility that the expression mechanism of homeostatic plasticity can be tailored to the needs of the network during different stages of development or in response to different challenges to network function.

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