Developmental Changes in Release Properties of the CA3-CA1 Glutamate Synapse in Rat Hippocampus

2004 ◽  
Vol 92 (5) ◽  
pp. 2714-2724 ◽  
Author(s):  
P. Wasling ◽  
E. Hanse ◽  
B. Gustafsson
Keyword(s):  
Developmental Change ◽  
Hippocampal Slices ◽  
Nmda Receptor Antagonist ◽  
Developmental Changes ◽  
Excitatory Postsynaptic Potential ◽  
Paired Pulse ◽  
Mk 801 ◽  
Release Probability ◽  
The Individual

Developmental changes in release probability ( Pr) and paired–pulse plasticity at CA3-CA1 glutamate synapses in hippocampal slices of neonatal rats were examined using field excitatory postsynaptic potential (EPSP) recordings. Paired-pulse facilitation (PPF) at these synapses was, on average, absent in the first postnatal week but emerged and became successively larger during the second postnatal week. This developmental increase in PPF was associated with a reduction in Pr, as indicated by the slower progressive block of the N-methyl-d-aspartate (NMDA) EPSP by the noncompetitive NMDA receptor antagonist MK-801. This developmental reduction in Pr was not homogenous among the synapses. As shown by the MK-801 analysis, the Pr heterogeneity observed among adult CA3-CA1 synapses is present already during the first postnatal week, and the developmental Pr reduction was found to be largely selective for synapses with higher Pr values, leaving Pr of the vast majority of the synapses essentially unaffected. A reduction in Pves, the release probability of the individual vesicle, possibly caused by reduction in Ca2+ influx, seems to explain the reduction in Pr. In vivo injection of tetanus toxin at the end of the first postnatal week did not prevent the increase in PPF, indicating that this developmental change in release is not critically dependent on normal neural activity during the second postnatal week.

scholarly journals Ketamine Produces a Long-Lasting Enhancement of CA1 Neuron Excitability

2021 ◽  
Vol 22 (15) ◽  
pp. 8091
Author(s):  
Grace Jang ◽  
M. Bruce MacIver
Keyword(s):  
Nmda Receptor ◽  
Potassium Channel ◽  
Receptor Antagonist ◽  
Hippocampal Slices ◽  
Nmda Receptor Antagonist ◽  
Channel Block ◽  
Mk 801 ◽  
Ca1 Region ◽  
Excitatory Transmission ◽  
Ketamine Anesthesia

Ketamine is a clinical anesthetic and antidepressant. Although ketamine is a known NMDA receptor antagonist, the mechanisms contributing to antidepression are unclear. This present study examined the loci and duration of ketamine’s actions, and the involvement of NMDA receptors. Local field potentials were recorded from the CA1 region of mouse hippocampal slices. Ketamine was tested at antidepressant and anesthetic concentrations. Effects of NMDA receptor antagonists APV and MK-801, GABA receptor antagonist bicuculline, and a potassium channel blocker TEA were also studied. Ketamine decreased population spike amplitudes during application, but a long-lasting increase in amplitudes was seen during washout. Bicuculline reversed the acute effects of ketamine, but the washout increase was not altered. This long-term increase was statistically significant, sustained for >2 h, and involved postsynaptic mechanisms. A similar effect was produced by MK-801, but was only partially evident with APV, demonstrating the importance of the NMDA receptor ion channel block. TEA also produced a lasting excitability increase, indicating a possible involvement of potassium channel block. This is this first report of a long-lasting increase in excitability following ketamine exposure. These results support a growing literature that increased GABA inhibition contributes to ketamine anesthesia, while increased excitatory transmission contributes to its antidepressant effects.

scholarly journals Mechanism Underlying Protective Effect of MK-801 against NMDA-Induced Neuronal Injury in vivo

1991 ◽  
Vol 11 (5) ◽  
pp. 779-785 ◽  
Author(s):  
Daisuke Uematsu ◽  
Joel H. Greenberg ◽  
Nobuo Araki ◽  
Martin Reivich
Keyword(s):  
Neuronal Injury ◽  
Nmda Receptor Antagonist ◽  
Free Calcium ◽  
Protective Effects ◽  
Acetoxymethyl Ester ◽  
Initial Oxidation ◽  
Signal Ratio ◽  
Mk 801 ◽  
Sharp Waves

The effects of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the dihydropyridine calcium antagonist nimodipine on NMDA-induced phenomena were investigated using an in vivo fluorometric technique with indo-1. Indo-1, a fluorescent cytosolic free calcium ([Ca2+]i) indicator, was loaded into the cat cortex approximately 500 μm in depth by super-fusion with the membrane-permeant indo-1 acetoxymethyl ester (indo-1-AM). Changes in [Ca2+]i signals (400 and 506 nm) and reduced nicotinamide adenine dinucleotide (NADH) fluorescence (464 nm) were simultaneously measured directly from the cortex during ultraviolet excitation (340 nm). Superfusion of 100 μM NMDA over the exposed cortex induced an elevation of the [Ca2+]i signal ratio (400/506 nm), biphasic changes in NAD/NADH redox state (initial oxidation followed by progressive reduction), and characteristic changes in the EEG (abrupt depression in amplitude followed by an excitatory pattern of 18–22 Hz poly spikes or sharp waves). These changes were completely blocked by treatment with MK-801 and reduced by nimodipine. The mechanism underlying the protective effects of systemically administered MK-801 on the NMDA-induced neuronal injury was verified in vivo.

Developmental increase in CA3-CA1 presynaptic function in the hippocampal slice

1995 ◽  
Vol 73 (5) ◽  
pp. 1821-1828 ◽  
Author(s):  
T. C. Dumas ◽  
T. C. Foster
Keyword(s):  
Hippocampal Slices ◽  
Age Groups ◽  
Extracellular Recording ◽  
Long Term Potentiation ◽  
Developmental Differences ◽  
Excitatory Postsynaptic Potential ◽  
Paired Pulse ◽  
Paired Pulse Facilitation ◽  
Presynaptic Function ◽  
Term Potentiation

1. We recorded extracellular and intracellular CA3-CA1 synaptic responses in hippocampal slices from neonatal rats [postnatal day (P) 15-21 and P29-35]. Presynaptic function was examined by measuring input-output relationships and paired-pulse facilitation and by quantal analysis of minimally evoked responses. 2. Extracellular recording revealed no difference in excitatory postsynaptic potential (EPSP) threshold or the fiber potential response for a given stimulus intensity between the two age groups. However, the slope of the field EPSP was consistently larger in older animals. The increase in EPSP slope was associated with a decrease in paired-pulse facilitation, suggesting an increase in presynaptic function with postnatal development. 3. Extracellular results were confirmed by intracellular recordings that revealed no difference in the minimal stimulation intensity needed to evoke a response, an increase in mean EPSP amplitude with development, and a decrease in paired-pulse facilitation. Quantal parameters were extracted by three separate methods including method of failures, coefficient of variance, and parameter optimization through noise deconvolution. All methods supported presynaptic mediation of facilitation. Comparison of quantal parameters during development indicated an increase in mean quantal content. 4. The results demonstrate that synaptic strength is altered over the course of development because of, at least in part, changes in presynaptic release mechanisms. Developmental differences in presynaptic function provide an explanation of differences in mechanisms for expression of long-term potentiation. The lower initial probability of transmitter release in neonates may permit increased presynaptic change.

scholarly journals Streptozotocin Inhibits Electrophysiological Determinants of Excitatory and Inhibitory Synaptic Transmission in CA1 Pyramidal Neurons of Rat Hippocampal Slices: Reduction of These Effects by Edaravone

2016 ◽  
Vol 40 (6) ◽  
pp. 1274-1288 ◽  
Author(s):  
Ting Ju ◽  
Yuru Li ◽  
Xiaoran Wang ◽  
Lifeng Xiao ◽  
Li Jiang ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Paired Pulse ◽  
Ca1 Pyramidal Neurons ◽  
Postsynaptic Currents ◽  
Pulse Ratio ◽  
Synaptic Mechanisms

Background: Streptozotocin (STZ) has served as an agent to generate an Alzheimer's disease (AD) model in rats, while edaravone (EDA), a novel free radical scavenger, has recently emerged as an effective treatment for use in vivo and vitro AD models. However, to date, these beneficial effects of EDA have only been clearly demonstrated within STZ-induced animal models of AD and in cell models of AD. A better understanding of the mechanisms of EDA may provide the opportunity for their clinical application in the treatment of AD. Therefore, the purpose of this study was to investigate the underlying mechanisms of STZ and EDA as assessed upon electrophysiological alterations in CA1 pyramidal neurons of rat hippocampal slices. Methods: Through measures of evoked excitatory postsynaptic currents (eEPSCs), AMPAR-mediated eEPSCs (eEPSCsAMPA), evoked inhibitory postsynaptic currents (eIPSCs), evoked excitatory postsynaptic current paired pulse ratio (eEPSC PPR) and evoked inhibitory postsynaptic current paired pulse ratio (eIPSC PPR), it was possible to investigate mechanisms as related to the neurotoxicity of STZ and reductions in these effects by EDA. Results: Our results showed that STZ (1000 µM) significantly inhibited peak amplitudes of eEPSCs, eEPSCsAMPA and eIPSCs, while EDA (1000 µM) attenuated these STZ-induced changes at holding potentials ranging from -60mV to +40 mV for EPSCs and -60mV to +20 mV for IPSCs. Our work also indicated that mean eEPSC PPR were substantially altered by STZ, effects which were partially restored by EDA. In contrast, no significant effects upon eIPSC PPR were obtained in response to STZ and EDA. Conclusion: Our data suggest that STZ inhibits glutamatergic transmission involving pre-synaptic mechanisms and AMPAR, and that STZ inhibits GABAergic transmission by post-synaptic mechanisms within CA1 pyramidal neurons. These effects are attenuated by EDA.

scholarly journals Characterization of Metabotropic Glutamate Receptor-Mediated Nitric Oxide Production in Vivo

1997 ◽  
Vol 17 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Anish Bhardwaj ◽  
Frances J. Northington ◽  
Lee J. Martin ◽  
Daniel F. Hanley ◽  
Richard J. Traystman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Calcium Release ◽  
Nmda Receptor Antagonist ◽  
No Production ◽  
Calcium Release Channel ◽  
Mk 801 ◽  
Metabotropic Glutamate

We tested the hypothesis that stimulation of metabotropic glutamate receptors (mGluRs) increases nitric oxide (NO) production in the hippocampus in vivo. Microdialysis probes were placed bilaterally into the CA3 region of the hippocampus of adult Sprague–Dawley rats under pentobarbital anesthesia. Probes were perfused for 5 h with artificial cerebrospinal fluid (CSF) containing 3 μM [14C]-L-arginine. Recovery of [14C]-L-citrulline in the effluent was used as a marker of NO production. In nine groups of rats, increases in [14C]-L-citrulline recovery were compared between right- and left-sided probes perfused with various combinations of the selective mGluR agonist, trans-(1 S,3 R)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD); the mGluR antagonist, (±)- α-methyl-4-carboxyphenylglycine (MCPG); the NO synthase inhibitor, N-nitro-L-arginine (LNNA); the ryanodine sensitive calcium-release channel inhibitor dantrolene, the non- N-methyl-D-aspartate (NMDA); receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5 H-dibenzo[ a,d] cyclohepten-5,10-imine (MK-801); and the Na+ channel blocker, tetrodotoxin. Recovery of [14C]-L-citrulline during perfusion with artificial CSF progressively increased to 90 ± 21 fmol/min (± SD) over 5 h. Perfusion in the contralateral hippocampus with 1 m M ACPD augmented [14C]-L-citrulline recovery to 250 ± 81 fmol/min. Perfusion of 1 m M nitroarginine + ACPD inhibited [14C]-L-citrulline recovery compared to that with ACPD alone. Perfusion with 1 m M MCPG + ACPD attenuated ACPD enhanced [14C]-L-citrulline recovery. Perfusion of 1 m M dantrolene + ACPD inhibited the ACPD-evoked increase in [14C]-L-citrulline recovery. Perfusion of 1 m M MCPG or dantrolene without ACPD did not decrease [14C]-L-citrulline recovery as compared to CSF alone. ACPD-enhanced [14C]-L-citrulline recovery was not attenuated by CNQX, MK-801, or tetrodotoxin (TTX). Using an indirect method of assessing NO production in vivo, these data demonstrate that mGluR stimulation enhances NO production in rat hippocampus. Inhibition with dantrolene suggests that calcium-induced calcium release amplifies the inositol triphosphate-mediated calcium signal associated with mGluR stimulation, thereby resulting in augmented calcium-dependent NO production.

Abnormal neuronal excitability in hippocampal slices from kindled rats

1985 ◽  
Vol 54 (5) ◽  
pp. 1295-1304 ◽  
Author(s):  
G. L. King ◽  
R. Dingledine ◽  
J. L. Giacchino ◽  
J. O. McNamara
Keyword(s):  
Dentate Gyrus ◽  
Hippocampal Slices ◽  
Burst Firing ◽  
Population Spike ◽  
Excitatory Postsynaptic Potential ◽  
Paired Pulse ◽  
Ca1 Region ◽  
Postsynaptic Potential ◽  
Kindled Seizures ◽  
Near Threshold

To determine if electrophysiological properties of hippocampal pathways are altered in kindled rats, extracellular recordings were made from hippocampal slices of rats kindled in the lateral entorhinal cortex and compared with those from implanted but unstimulated controls. Studies were made either 24 h or 28 days after the last kindled seizure and done in normal (3.5 mM) or elevated (7 mM) K+. The preparation of slices, data accumulation, and data analyses were done blind. One day or 28 days after the last kindled seizure, the proportion of slices with spontaneous epileptiform bursts recorded from the CA2/3 region in elevated K+ was significantly (P less than 0.001) increased in the kindled animals. The frequency of spontaneous burst firing was also increased and reached significance (P less than 0.02) at 28 days following the last kindling stimulus. One day after the last kindling stimulus, paired-pulse (GABAergic) inhibition in the CA1 region was decreased (P less than 0.001). Several measures suggested an increased synaptic inhibition in the dentate gyrus of slices from the kindled groups 1 day after kindling. Paired-pulse inhibition was increased (P less than 0.01), the current required to evoke a near-threshold population spike was increased (P less than 0.05), and the population spike amplitude was reduced for a given field excitatory postsynaptic potential (EPSP) (P less than 0.01). Twenty-eight days after the last kindling stimulus, however, paired-pulse inhibition in the dentate was slightly less in slices from kindled rats (P less than 0.005). In other respects the CA1 and dentate regions did not differ between kindled and control groups within 24 h of the last stage V seizure. Thus the maximum amplitudes of presynaptic fiber volley, population spike, and field-excitatory postsynaptic potential (EPSP) slope, and the number of population spikes evoked by a near-maximally effective afferent stimulus, were unchanged. In the CA1 region the input-output curve of field EPSP versus population spike, and the current intensity required to evoke a near-threshold population spike were also unchanged. In addition, no spontaneous bursts were recorded from CA1 in 3.5 mM K+. We conclude that either synapses or neurons intrinsic to the hippocampus are altered by kindling stimuli applied outside this brain area. The transient increase in inhibition in the dentate gyrus suggests that it may reflect a compensatory reaction to kindled seizures. In contrast, the long-lasting (at least 28 days) increase in burst firing in CA2/3 may represent a mechanism for the initiation or propagation of kindled seizures.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals How synaptic strength, short-term plasticity, and temporal factors contribute to neuronal spike output

2021 ◽  
Author(s):  
Alexandra Gastone Guilabert ◽  
Benjamin Ehret ◽  
Moritz O. Buchholz ◽  
Gregor F.P. Schuhknecht
Keyword(s):  
Background Activity ◽  
Synaptic Strength ◽  
Temporal Coding ◽  
Excitatory Postsynaptic Potential ◽  
Short Term ◽  
Paired Pulse ◽  
Temporal Synchrony ◽  
Short Term Plasticity ◽  
Firing Rates

To compute spiking responses, neurons integrate inputs from thousands of synapses whose strengths span an order of magnitude. Intriguingly, in mouse neocortex, the small minority of 'strong' synapses is found predominantly between similarly tuned cells, suggesting they are the synapses that determine a neuron's spike output. This raises the question of how other computational primitives, such as 'background' activity from the majority of synapses, which are 'weak', short-term plasticity, and temporal synchrony contribute to spiking. First, we combined extracellular stimulation and whole-cell recordings in mouse barrel cortex to map the distribution of excitatory postsynaptic potential (EPSP) amplitudes and paired-pulse ratios of excitatory synaptic connections converging onto individual layer 2/3 (L2/3) neurons. While generally net short-term plasticity was weak, connections with EPSPs > 2 mV displayed pronounced paired-pulse depression. EPSP amplitudes and paired-pulse ratios of connections converging onto the same neurons spanned the full range observed across L2/3 and there was no indication that strong synapses nor those with particular short-term plasticity properties were associated with particular cells, which critically constrains theoretical models of cortical filtering. To investigate how different computational primitives of synaptic information processing interact to shape spiking, we developed a computational model of a pyramidal neuron in the rodent L2/3 circuitry: firing rates and pairwise correlations of presynaptic inputs were constrained by in vivo observations, while synaptic strength and short-term plasticity were set based on our experimental data. Importantly, we found that the ability of strong inputs to evoke spiking critically depended on their high temporal synchrony and high firing rates observed in vivo and on synaptic background activity - and not primarily on synaptic strength, which in turn further enhanced information transfer. Depression of strong synapses was critical for maintaining a neuron's responsivity and prevented runaway excitation. Our results provide a holistic framework of how cortical neurons exploit complex synergies between temporal coding, synaptic properties, and noise in order to transform synaptic inputs into output firing.

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