To study the role of long-term depression (LTD) in the mechanisms of learning and memory in hippocampus of rat, recordings were taken from freely moving animals that had undergone chronic implantation of a recording electrode in the hippocampus CA1 region and a bipolar stimulating electrode in the ipsilateral Schaffer collateral-commissural pathway. The recording electrode was inserted 3.8 mm posterior to bregma and 2.8 mm right of the midline, and the stimulating electrode was inserted 4.8 mm posterior to bregma and 3.8 mm right of the midline via holes drilled through the skull. The entire assembly was connected with a rubber socket on the animal's head and then stabilized with dental cement. The correct placement of the electrodes into the hippocampal CA1 area was confirmed via electrophysiological criteria and postmortem histological analysis. After 2 weeks of surgery recovery, the rats were placed in the familiar recording chamber for 3 days. The field excitatory postsynaptic potentials (fEPSPs) were evoked by stimulating with a square wave constant current pulse of 0.2 ms duration, at a frequency of 0.033 Hz and at a stimulation intensity adjusted to given an fEPSP amplitude of 50% of the maximum, and the baseline of fEPSPs were recorded for 3 days in the familiar recording environment at the same time each day. A novelty environment that was made of clear Perspex (40 cm x 40 cm x 40 cm) was prepared and we examined whether exposure to a novelty spatial environment facilitated the expression of activity-dependent persistent decrease in synaptic transmission (namely LTD) at CA1 synapses in the rat hippocampus. The results showed that brief exposure to a novelty environment for 10 min facilitated the expression of LTD in the hippocampal CA1 area under no other exogenous high- or low-frequency stimulation protocol. This facilitatory effect was dependent on the activation of D1/D5 receptors: the D1/D5 receptors antagonist SCH23390 prevented the decrease of synaptic transmission in the hippocampus during the novelty exploration. These data provided important evidence that LTD may underlie certain forms of learning and memory and that dopamine participates in the synaptic plasticity in the process of hippocampal spatial information storage.
Animals ; CA1 Region, Hippocampal ; physiology ; Dopamine ; physiology ; Electrodes ; Excitatory Postsynaptic Potentials ; Exploratory Behavior ; Neuronal Plasticity ; Rats

AIMTo investigate the influence of the vagus nerve on the electrophysiological properties in the Mauthner cell soma and the relationship between soma and viscus.

METHODSThe microelectrode recording technique was used to explore the electrophysiological properties in the Mauthner cell when stimulating the right vagus.

RESULTSAt lower stimulation strength a graded and compound excitatory postsynaptic potentials (EPSP), formed by two components with lower amplitude, were recorded on the Mauthner cell in a crucian carp. As the intensity of stimulus increased, the amplitude became larger and lasting time longer. With the stimulations high enough, action potentials (AP) were evoked on the EPSP.

CONCLUSION(1) Action potential can be induced on M cell by a direct stimulation on vagus nerve, which is in controversy with previous reports. (2) The neural pathway projecting from vagus to M cell is composed of a set of neuronal chains with excitatory and/or inhibitory members, the activation of M cell depends on the relationship between excitatory and inhibitory neuron.

Animals ; Carps ; physiology ; Excitatory Postsynaptic Potentials ; physiology ; Microelectrodes ; Neurons ; physiology ; Vagus Nerve ; physiology

PURPOSE: Modafinil is a wake-promoting agent that has been proposed to improve cognitive performance at the preclinical and clinical levels. Since there is insufficient evidence for modafinil to be regarded as a cognitive enhancer, the aim of this study was to investigate the effects of chronic modafinil administration on behavioral learning in healthy adult rats. METHODS: Y-maze training was used to assess learning performance, and the whole-cell patch clamp technique was used to assess synaptic transmission in pyramidal neurons of the hippocampal CA1 region of rats. RESULTS: Intraperitoneal administration of modafinil at 200 mg/kg or 300 mg/kg significantly improved learning performance. Furthermore, perfusion with 1mM modafinil enhanced the frequency and amplitude of spontaneous postsynaptic currents and spontaneous excitatory postsynaptic currents in CA1 pyramidal neurons in hippocampal slices. However, the frequency and amplitude of spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons were inhibited by treatment with 1mM modafinil. CONCLUSIONS: These results indicate that modafinil improves learning and memory in rats possibly by enhancing glutamatergic excitatory synaptic transmission and inhibiting GABAergic (gamma-aminobutyric acid-ergic) inhibitory synaptic transmission.
Adult ; Animals ; CA1 Region, Hippocampal ; Excitatory Postsynaptic Potentials ; Humans ; Inhibitory Postsynaptic Potentials ; Learning* ; Memory ; Neurons ; Perfusion ; Rats* ; Synaptic Potentials ; Synaptic Transmission*

OBJECTIVETo investigate the development of the electrophysiological property of bushy cells in the anterior ventral cochlear nucleus (AVCN) of neonatal Sprague Dawley (SD) rats.

METHODSThe development of action potential and spontaneous miniature excitatory postsynaptic currents (mEPSCs) in AVCN bushy cells were investigated by whole-cell patch-clamp technique in SD rats during the postnatal days 5-21 (P5-21). The half band width of the action potential (AP), 10%-90% risetime and decay tau of the mEPSCs were analyzed.

RESULTSThe AP of the bushy cells became faster with age from P5 to P21 and stopped changing around the period of hearing onset, as evidenced by the alteration of half band width of the AP. The time accuracy of mEPSCs of the bushy cells also increased with age and stabilized around hearing onset as shown by briefer 10%-90% rise time and decay tau of mEPSCs in P14/P21 than in P7.

CONCLUSIONThe functional refinement of the bushy cells in the AVCN precedes hearing onset in neonatal rats.

Action Potentials ; Animals ; Cochlear Nucleus ; cytology ; Excitatory Postsynaptic Potentials ; Hearing ; Neurons ; cytology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Synapses

OBJECTIVETo observe the microstructure of the cell membrane of epileptic neurons using atomic force microscopy (AFM).

METHODSModel of epileptic neurons was established by subjecting the neurons culture for 14 days in vitro to magnesium-free media treatment for 3 h. Patch clamp technique was applied to record the electrophysiological activity of the epileptic neurons. AFM was performed to observe and measure the microstructure of the cell membrane of the epileptic neuron.

RESULTSAfter a 3-hour treatment with magnesium-free media, the epileptic neurons displayed sustained epileptiform discharge, which continued after the neurons were returned to normal medium culture on day 14. Under AFM scanning size of 80 microm x 80 microm and 2 microm x 2 microm, no obvious difference in the morphology of the cell membrane was noted between epileptic and normal neurons; under the scanning size of 500 nm x 500 nm, small pits occurred in the cell membrane in both groups, but no significant difference was found in the dimension of the pits between the two groups (the diameter and depth of the pits was 114.86-/+9.33 nm and 5.71-/+0.69 nm in epileptic neurons, and 116.4-/+9.13 nm and 5.69-/+0.71 nm in the control neurons, respectively, P>0.05).

CONCLUSIONAFM provides a new method for observing neuronal membrane microstructure at nanometer resolutions. No significant alterations occur in the membrane of the neurons after a 3-hour magnesium-free media treatment.

Cell Membrane ; ultrastructure ; Cells, Cultured ; Culture Media ; Epilepsy ; pathology ; Excitatory Postsynaptic Potentials ; Inhibitory Postsynaptic Potentials ; Magnesium ; Microscopy, Atomic Force ; Neurons ; ultrastructure ; Patch-Clamp Techniques

Amyotrophic lateral sclerosis (ALS) is a degenerative neuromuscular disease of unknown etiology in which the upper and lower motor neurons are progressively destroyed. Recent evidences support the role of autoimmune mechanisms in the pathogenesis of ALS. This study investigated the effects of sera from ALS patients on neuromuscular transmission in phrenic nerve-hemidiaphragm preparations and on calcium currents of single isolated dorsal root ganglion (DRG) cells in mice. Mice were injected with either control sera from healthy adults or ALS sera from 18 patients with ALS of sporadic form, for three days. Miniature end plate potential (MEPP) and nerve-evoked end plate potential (EPP) were measured using intracellular recording technique and the quantal content was determined. Single isolated DRG cells were voltage-clamped with the whole-cell configuration and membrane currents were recorded. Sera from 14 of 18 ALS patients caused a significant increase in MEPP frequency in normal Ringer's solution (4.62+/-0.14 Hz) compared with the control (2.18+/-0.15 Hz). In a high Mg2+/low Ca2+ solution, sera from 13 of 18 ALS patients caused a significant increase in MEPP frequency, from 2.18+/-0.31 Hz to 6.09+/-0.38 Hz. Sera from 11 of 18 patients produced a significant increase of nerve-evoked EPP amplitude, from 0.92+/-0.05 mV to 1.30+/-0.04 mV, while the other seven ALS sera did not alter EPP amplitude. In the ALS group, EPP quantal content was also elevated by the sera of 14 patients (from 1.49+/-0.07 to 2.35+/-0.07). MEPP frequency and amplitude in wobbler mouse were 4.03+/-0.53 Hz and 1.37+/-0.18 mV, respectively, which were significantly higher than those of wobbler controls (wobblers without the symptoms of wobbler). Sera from ALS patients significantly reduced HVA calcium currents of DRG cells to 42.7% at -10 mV. Furthermore, the inactivation curve shifted to more negative potentials with its half-inactivation potential changed by 6.98 mV. There were, however, significant changes neither in the reversal potential of ICa nor in the I-V curve. From these results it was concluded that: 1) The serum factors of sporadic ALS patients increase neuromuscular transmission and can alter motor nerve terminal presynaptic function. This suggests that ALS serum factors may play an important role in the early stage of ALS, and 2) Calcium currents in DRG cells were reduced and rapidly inactivated by ALS sera, suggesting that in these cells, ALS serum factors may exert interaction with the calcium channel.
Adult ; Amyotrophic Lateral Sclerosis* ; Animals ; Calcium Channels* ; Calcium* ; Diagnosis-Related Groups ; Excitatory Postsynaptic Potentials ; Ganglia, Spinal ; Humans ; Membranes ; Mice* ; Miniature Postsynaptic Potentials ; Motor Neurons ; Neuromuscular Diseases ; Neuromuscular Junction

Epilepsy is a disease characterized by "paroxysmal, hypersynchronous, and excessive electrical discharges". Despite long and extensive research on epileptogenesis, clear explanation of the basic mechanisms of epilepsy has yet to be established. Considering the diverse etiologies of epilepsy and experimental seizure models, a seizure has many mecha-nisms affecting single neurons and its neural circuits. Epileptic neuron has the ability of spontaneous depolarization and firing. To achieve depolarization, these neurons tend to have increased membrane excitability by interaction of neuro-transmitter receptors and ion channels and synapses, but excitable single neuron does not necessarily mean hyperex-citable neural circuit. Synchrony, burst, and neural interactions are required for the spreading of the electrical dis-charges. Increased membrane excitability is mainly achieved by increased influx of calcium and decreased potassium and chloride transport mechanism. With this membrane excitability, paroxysmal depolarization shift (PDS) needs synaptic excitation represented by giant EPSP. Synaptic function is mainly controlled by neurotransmitters such as GABA and glutamate. The imbalance of these important neurotransmitters has a crucial role in epilepsy. Synaptic reor-ganization and associated change of neurotransmitter plays an essential role in chronic epileptogenesis.
Calcium ; Epilepsy ; Excitatory Postsynaptic Potentials ; Fires ; gamma-Aminobutyric Acid ; Glutamic Acid ; Ion Channels ; Membranes ; Neurons ; Neurotransmitter Agents ; Potassium ; Seizures ; Synapses

PURPOSE: This study aimed to evaluate the potential allergenicity of genetically modified (GM) herbicide-resistant food by using the serum screenning test. METHODS: Children with allergic disease were recruited, and those who were sensitized to soybean, corn or peanut were selected to obtain their sera. Sensitization to these food allergens was determined when the level of specific IgE was over 0.35 kU/L using ImmunoCAP (Pharmacia, Uppsala, Sweden). Immunoblot analyses were performed for soybean (n=50), corn (n=50) and peanut (n=20). Newly inserted gene was sequenced and cloned from GM soy (Roundup Ready Soybean, Monsanto), GM corn (Bt 11, Syngenta) and GM canola (MS8/RF3 canola, Bayer CropScience). These proteins, such as CP4 EPSPS, PAT, and BAR, were expressed and purified for the serum screening test. RESULTS: Immunoblot analysis using CP4 EPSPS and sera from soybean-sensitized children showed no bands. Likewise, sera from corn-sensitized children and PAT did not demonstrate IgE binding in immunoblot analysis. In addition, there were no reactions between BAR and sera from peanut-sensitized patients. CONCLUSION: The serum screening test using sera from allergic children and newly inserted protein (CP4 EPSPS, PAT and BAR) in GM soybean, GM corn and GM canola failed to show IgE binding in immunoblot analysis. The results of this study suggest that these newly inserted proteins may not cause allergic disease. Further studies using more sera from allergic children are needed to conclude the safety of herbicide-resistant GM food.
Allergens ; Child ; Clone Cells ; Excitatory Postsynaptic Potentials ; Food, Genetically Modified ; Humans ; Immunoglobulin E ; Mass Screening ; Proteins ; Soybeans ; Zea mays

BACKGROUNDIncreasing age was shown to decrease the requirements for propfol. However, the mechanisms of ageing-induced potentiation of anesthetic actions have not been clearly explored. The aim of this study is to compare the effects of propofol on the field excitatory postsynaptic potentials (fEPSPs) in hippocampal slices of young and aging mice.

METHODSBrain slices were prepared from C57BL6 male young (2 months) and aging (>12 months) mice. The dendritic field excitatory postsynaptic potential was recorded from the CA1 stratum radiatum using patch clamp electrophysiological methods. A bipolar concentric stimulating electrode was placed along the Schaffer collateral for othodromic stimulation. The effects of clinically-relevant concentrations of propofol were studied in the young and ageing mouse tissues.

RESULTSPropofol application increased the orthodromically evoked fEPSP produced in slices taken from young and older animals. A striking feature in the I/O relationship was the decreased enhancement of the fEPSPs by propofol in slices from older mice. A clinically relevant concentration of propofol, 10 µmol/L, showed more significant enhancement in amplitude and area under the curve (AUC) of fEPSP in young compared to tissues from older mice (amplitude: young (24.9 ± 3.4)%, old (4.6 ± 1.6)%; AUC young (30.6 ± 5.4)%, old (2.1 ± 1.7)%). There was no statistically significant difference between the paired-pulse facilitation (PPF) ratios calculated for the responses obtained in tissues from young mice. In slices from older mice, in the presence of 10 µmol/L propofol, PPF was decreased and returned to baseline after washout (baseline 1.21 ± 0.01, propofol: 1.16 ± 0.01). Bicuculline (15 µmol/L) blocked the enhancement of propofol on fEPSP in tissues from young and old mice.

CONCLUSIONThe fEPSP of slices from aging mice demonstrates diminished sensitivity to the enhancing actions of propofol.

Animals ; CA1 Region, Hippocampal ; drug effects ; metabolism ; Excitatory Postsynaptic Potentials ; drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Propofol ; pharmacology

The aim of the present study is to observe the receptor kinetics property of long-term potentiation (LTP) of excitatory postsynaptic potential (EPSP) in spinal cord motoneurons (MNs) by descending activation. The intracellular recording techniques were conducted in spinal cord MNs of neonatal rats aged 8-14 days. The changes of EPSP induced by ipsilateral ventrolateral funiculus (iVLF) stimulation (iVLF-EPSPs) were observed, and receptor kinetics of iVLF-EPSPs were analyzed. The results showed that, the amplitude, area under curve and maximum left slope of EPSP were positively correlated with stimulus intensity (P < 0.05 or P < 0.01), while the apparent receptor kinetic parameters apparent dissociation rate constant (K(2)), apparent equilibrium dissociation constant (K(T)) of EPSP were negatively correlated with stimulus intensity (P < 0.01 or P < 0.05). The iVLF-EPSPs were persistently increased after tetanic stimulation (100 Hz, 50 pulses/train, duration 0.4-1.0 ms, 6 trains, main interval 10 s, 10-100 V) in 5 of 11 tested MNs. The amplitude of iVLF-EPSPs was potentiated to more than 120% of baseline and lasted at least 30 min, which could be referred to as iVLF-LTP. Meanwhile, the area under curve and maximum left slope of EPSPs were also increased to more than 120% of baseline. During iVLF-LTP, apparent receptor kinetics analyses of iVLF-EPSPs indicated that K(2) and KT were decreased significantly to less than 80% of the baseline within 10 min and gradually and partially recovered in 3 MNs. These results of receptor kinetics analyses of iVLF-EPSPs suggest a possible enhancement in affinity of postsynaptic receptors in the early stage of iVLF-LTP in some MNs.
Animals ; Excitatory Postsynaptic Potentials ; Kinetics ; Long-Term Potentiation ; Motor Neurons ; physiology ; Rats ; Spinal Cord ; cytology ; Synaptic Transmission