1.Effects of Modafinil on Behavioral Learning and Hippocampal Synaptic Transmission in Rats.
Wen Wen YAN ; Li Hua YAO ; Chong CHEN ; Hai Xia WANG ; Chu Hua LI ; Jun Ni HUANG ; Peng XIAO ; Cheng Yi LIU
International Neurourology Journal 2015;19(4):220-227
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*
2.Effects and mechanisms of morphine on synaptic transmission of hippocampal neurons of rat.
Wei-dong YUE ; Yun-hong ZHANG ; Yu-rong LI ; Shu-zhuo ZHANG ; Lei YANG
Chinese Journal of Applied Physiology 2003;19(2):150-153
AIMTo investigate the effects of morphine on synaptic transmission of neurons of central nervous system and reveal the mechanism underlying it.
METHODSNew born wistar rats were used for primary culture of hippocampus neurons. Using whole-cell patch-clamp technique, we observed the excitatory and spontaneous inhibitory postsynaptic current (EPSC, sIPSC) and glutamate-induced current before and after morphine treatment.
RESULTS(1) sEPSC of hippocampal neurons was markedly increased after morphine application. The effect of morphine was blocked by opioid antagonist naloxone (n=18, P < 0.01). (2) The frequency of mEPSC and the amplitude of glutamate-induced current of hippocampal neurons had no significant changes after morphine treatment (P > 0.05). (3) Morphine inhibited sIPSC of hippocampal neurons markedly and naloxone could block this effect (n=13, P < 0.01).
CONCLUSIONThe results suggest that the exciting effect of morphine on hippocampal neurons are not due to direct influence of morphine on glutamate synapses transmission, but may result from the inhibition on interneurons, that is "disinhibition" way.
Animals ; Animals, Newborn ; Cells, Cultured ; Excitatory Postsynaptic Potentials ; physiology ; Hippocampus ; cytology ; Inhibitory Postsynaptic Potentials ; Morphine ; pharmacology ; Neurons ; drug effects ; physiology ; Patch-Clamp Techniques ; Rats ; Rats, Wistar ; Synaptic Transmission ; drug effects ; physiology
3.Inhibitory and Excitatory Postsynaptic Currents of Medial Vestibular Nucleus Neurons of Rats.
Sang Woo CHUN ; Jeong Hee CHOI ; Byung Rim PARK
The Korean Journal of Physiology and Pharmacology 2003;7(2):59-64
The medial vestibular nucleus (MVN) neurons are controlled by excitatory synaptic transmission from the vestibular afferent and commissural projections, and by inhibitory transmission from interneurons. Spontaneous synaptic currents of MVN neurons were studied using whole cell patch clamp recording in slices prepared from 13- to 17-day-old rats. The spontaneous inhibitory postsynaptic currents (sIPSCs) were significantly reduced by the GABAA antagonist bicuculline (20micrometer), but were not affected by the glycine antagonist strychnine (1micrometer). The frequency, amplitude, and decay time constant of sIPSCs were 4.3 0.9 Hz, 18.1 2.0 pA, and 8.9 0.4 ms, respectively. Spontaneous excitatory postsynaptic currents (sEPSCs) were mediated by non-NMDA and NMDA receptors. The specific AMPA receptor antagonist GYKI-52466 (50micrometer) completely blocked the non-NMDA mediated sEPSCs, indicating that they are mediated by an AMPA-preferring receptor. The AMPA mediated sEPSCs were characterized by low frequency (1.5 0.4 Hz), small amplitude (13.9 1.9 pA), and rapid decay kinetics (2.8 0.2 ms). The majority (15/21) displayed linear I-V relationships, suggesting the presence of GluR2-containing AMPA receptors. Only 35% of recorded MVN neurons showed NMDA mediated currents, which were characterized by small amplitude and low frequency. These results suggest that the MVN neurons receive excitatory inputs mediated by AMPA, but not kainate, and NMDA receptors, and inhibitory transmission mediated by GABAA receptors in neonatal rats.
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Animals
;
Bicuculline
;
Excitatory Postsynaptic Potentials*
;
Glycine
;
Inhibitory Postsynaptic Potentials
;
Interneurons
;
Kainic Acid
;
Kinetics
;
N-Methylaspartate
;
Neurons*
;
Rats*
;
Receptors, AMPA
;
Receptors, N-Methyl-D-Aspartate
;
Strychnine
;
Synaptic Transmission
;
Vestibular Nuclei*
4.Peripheral Nerve Injury Alters Excitatory and Inhibitory Synaptic Transmission in Rat Spinal Cord Substantia Gelatinosa.
The Korean Journal of Physiology and Pharmacology 2005;9(3):143-147
Following peripheral nerve injury, excessive nociceptive inputs result in diverse physiological alterations in the spinal cord substantia gelatinosa (SG), lamina II of the dorsal horn. Here, I report the alterations of excitatory or inhibitory transmission in the SG of a rat model for neuropathic pain ("spared nerve injury"). Results from whole-cell recordings of SG neurons show that the number of distinct primary afferent fibers, identified by graded intensity of stimulation, is increased at 2 weeks after spared nerve injury. In addition, short-term depression, recognized by paired-pulse ratio of excitatory postsynaptic currents, is significantly increased, indicating the increase of glutamate release probability at primary afferent terminals. The peripheral nerve injury also increases the amplitude, but not the frequency, of spontaneous inhibitory postsynaptic currents. These data support the hypothesis that peripheral nerve injury modifies spinal pain conduction and modulation systems to develop neuropathic pain.
Animals
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Depression
;
Excitatory Postsynaptic Potentials
;
Glutamic Acid
;
Horns
;
Inhibitory Postsynaptic Potentials
;
Models, Animal
;
Neuralgia
;
Neurons
;
Patch-Clamp Techniques
;
Peripheral Nerve Injuries*
;
Peripheral Nerves*
;
Rats*
;
Spinal Cord*
;
Substantia Gelatinosa*
;
Synaptic Transmission*
5.Isoliquiritigenin, a Chalcone Compound, Enhances Spontaneous Inhibitory Postsynaptic Response.
Junsung WOO ; Suengmok CHO ; C Justin LEE
Experimental Neurobiology 2014;23(2):163-168
Isoliquiritigenin (ILTG) is a chalcone compound and shows various pharmacological properties, including antioxidant and anti-inflammatory activities. In recent study, we have reported a novel role of ILTG in sleep through a positive allosteric modulation of gamma-aminobutyric acid type A (GABA(A))-benzodiazepine (BZD) receptors. However, the effect of ILTG in GABA(A)R-mediated synaptic response in brain has not been tested yet. Here we report that ILTG significantly prolonged the decay of spontaneous inhibitory postsynaptic currents (sIPSCs) mediated by GABA(A)R in mouse hippocampal CA1 pyramidal neurons without affecting amplitude and frequency of sIPSCs. This enhancement was fully inhibited by flumazenil (FLU), a specific GABA(A)-BZD receptor antagonist. These results suggest a potential role of ILTG as a modulator of GABAergic synaptic transmission.
Animals
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Brain
;
Chalcone*
;
Flumazenil
;
gamma-Aminobutyric Acid
;
Inhibitory Postsynaptic Potentials
;
Mice
;
Neurons
;
Synaptic Transmission
6.Noradrenergic Modulation of Spontaneous Inhibitory Postsynaptic Currents in the Hypothalamic Paraventricular Nucleus.
Long Hwa LEE ; Wonee CHONG ; Kiho LEE ; Jin Bong PARK ; Pan Dong RYU
The Korean Journal of Physiology and Pharmacology 2002;6(2):71-80
Previous studies have suggested that brain stem noradrenergic inputs differentially modulate neurons in the paraventricular nucleus (PVN). Here, we compared the effects of norepinephrine (NE) on spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) in identified PVN neurons using slice patch technique. In 17 of 18 type I neurons, NE (30-100microM) reversibly decreased sIPSC frequency to 41+/-7% of the baseline value (4.4+/-0.8 Hz, p<0.001). This effect was blocked by yohimbine (2-20microM), an alpha2-adrenoceptor antagonist and mimicked by clonidine (50 microM), an alpha2-adrenoceptor agonist. In contrast, NE increased sIPSC frequency to 248+/-32% of the control (3.06+/-0.37 Hz, p<0.001) in 31 of 54 type II neurons, but decreased the frequency to 41+/-7% of the control (5.5+/-1.3 Hz) in the rest of type II neurons (p<0.001). In both types of PVN neurons, NE did not affect the mean amplitude and decay time constant of sIPSCs. In addition, membrane input resistance and amplitude of sIPSC of type I neurons were larger than those of type II neurons tested (1209 vs. 736 M omega, p<0.001; 110 vs. 81 pS, p<0.001). The results suggest that noradrenergic modulation of inhibitory synaptic transmission in the PVN decreases the neuronal excitability in most type I neurons via alpha2-adrenoceptor, however, either increases in about 60% or decreases in 40% of type II neurons.
Brain Stem
;
Clonidine
;
Inhibitory Postsynaptic Potentials*
;
Membranes
;
Neurons
;
Norepinephrine
;
Paraventricular Hypothalamic Nucleus*
;
Synaptic Transmission
;
Yohimbine
7.Roles of Metabotropic Glutamate Receptors in Inhibitory Synaptic Transmission in Rat Medial Vestibular Nucleus Neurons.
Journal of the Korean Neurological Association 2003;21(3):273-282
BACKGROUND: The medial vestibular nucleus (MVN) is involved in the reflex control of the head and eyes, and the recovery of vestibular function after vestibular lesions. This study was performed to investigate the characteristics of inhibitory postsynaptic currents (IPSC) and the roles of metabotropic glutamate receptors on inhibitory synaptic transmissions. METHODS: Whole cell patch clamp recordings were carried out from MVN neurons in brainstem slice of neonatal rats. RESULTS: The frequency and amplitude of the IPSC were significantly reduced by GABAA a n t a g o n i s t bicuculline (20 microM) but were not affected by the glycine antagonist strychnine (1 microM). The baseline frequency, amplitude and decay time constant of spontaneous IPSC (sIPSC) were 4.9+/-1.8 Hz, 25.9+/-3.1 pA, 8.7+/-0.5 ms, respectively. Glutamate (1 mM) increased the frequency of sIPSC, but decreased that of the miniature IPSC (mIPSC) in MVN neurons. Such dual effects of glutamate were mimicked by group I, II metabotropic glutamate receptor (mGluR) agonist ACPD (20 microM). The specific mGluR 2, 3 agonist DCG-IV (3 microM) reduced mIPSC frequency, but did not increase sIPSC frequency. The mGluR 1, 5 agonist DHPG (100 microM) increased sIPSC and mIPSC frequency. CONCLUSIONS: These data suggest that the IPSC recorded from MVN neurons are mediated mainly by GABAA receptors and glutamate-induced modulations of inhibitory synaptic transmissions can influence the excitability of MVN neurons.
Animals
;
Bicuculline
;
Brain Stem
;
Glutamic Acid
;
Glycine
;
Head
;
Inhibitory Postsynaptic Potentials
;
Neurons*
;
Rats*
;
Receptors, Metabotropic Glutamate*
;
Reflex
;
Strychnine
;
Synaptic Transmission*
;
Vestibular Nuclei*
8.Actions of Orphan Opioid on the Membrane Conductances and Synaptic Transmission in Rat Medial Vestibular Nucleus Neurons.
Hyun Young PARK ; Hyuk CHANG ; Jeong Hee CHOI ; Moon Young LEE ; Kwang Ho JO ; Byung Rim PARK ; Sang Woo CHUN
Journal of the Korean Neurological Association 2004;22(6):631-637
BACKGROUND: The medial vestibular nucleus (MVN) is involved in the reflex control of the head and eyes, and the recovery of vestibular function after vestibular injuries. This study was performed to investigate the actions of the orphan opioid (nociceptin) on the membrane conductances and synaptic transmission in rat MVN neurons. METHODS: Whole cell patch clamp recordings were carried out in the brainstem slice of neonatal rats. RESULTS: Nociceptin (2 micro M) inhibited the spontaneous discharge in the majority (83%) of MVN neurons. This inhibition was insensitive to the non-specific opioid receptor antagonist naloxone (10 micro M), but was effectively antagonized by the selective opioid receptor-like 1 (ORL1) receptor antagonist, [Nphe1] nociceptin(1-13)NH2 (3 micro M). Nociceptin had no effect on the rate or amplitude of miniature inhibitory postsynaptic currents (mIPSCs). Nociceptin induced an outward current, and which was blocked by [Nphe1] nociceptin(1-13)NH2 in MVN neurons. Outward current reversed at -81 +/- 2 mV, which was close to the K+ equilibrium potential as calculated by the Nernst equation in 6 mM extracellular potassium solution. This indicates that the action of nociceptin involves postsynaptic receptors on the MVN neurons. CONCLUSIONS: These results suggest that nociceptin modulate neuronal excitability by activating a K+ conductance in postsynaptic neurons, not by modulation of synaptic transmission in MVN neurons.
Animals
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Brain Stem
;
Child
;
Child, Orphaned*
;
Head
;
Humans
;
Inhibitory Postsynaptic Potentials
;
Membranes*
;
Naloxone
;
Neurons*
;
Potassium
;
Rats*
;
Receptors, Opioid
;
Reflex
;
Synaptic Transmission*
;
Vestibular Nuclei*
9.Layer-specific cholinergic modulation of synaptic transmission in layer 2/3 pyramidal neurons of rat visual cortex
Kwang Hyun CHO ; Seul Yi LEE ; Kayoung JOO ; Duck Joo RHIE
The Korean Journal of Physiology and Pharmacology 2019;23(5):317-328
It is known that top-down associative inputs terminate on distal apical dendrites in layer 1 while bottom-up sensory inputs terminate on perisomatic dendrites of layer 2/3 pyramidal neurons (L2/3 PyNs) in primary sensory cortex. Since studies on synaptic transmission in layer 1 are sparse, we investigated the basic properties and cholinergic modulation of synaptic transmission in layer 1 and compared them to those in perisomatic dendrites of L2/3 PyNs of rat primary visual cortex. Using extracellular stimulations of layer 1 and layer 4, we evoked excitatory postsynaptic current/potential in synapses in distal apical dendrites (L1-EPSC/L1-EPSP) and those in perisomatic dendrites (L4-EPSC/L4-EPSP), respectively. Kinetics of L1-EPSC was slower than that of L4-EPSC. L1-EPSC showed presynaptic depression while L4-EPSC was facilitating. In contrast, inhibitory postsynaptic currents showed similar paired-pulse ratio between layer 1 and layer 4 stimulations with depression only at 100 Hz. Cholinergic stimulation induced presynaptic depression by activating muscarinic receptors in excitatory and inhibitory synapses to similar extents in both inputs. However, nicotinic stimulation enhanced excitatory synaptic transmission by ~20% in L4-EPSC. Rectification index of AMPA receptors and AMPA/NMDA ratio were similar between synapses in distal apical and perisomatic dendrites. These results provide basic properties and cholinergic modulation of synaptic transmission between distal apical and perisomatic dendrites in L2/3 PyNs of the visual cortex, which might be important for controlling information processing balance depending on attentional state.
Animals
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Automatic Data Processing
;
Dendrites
;
Depression
;
Inhibitory Postsynaptic Potentials
;
Kinetics
;
Pyramidal Cells
;
Rats
;
Receptors, AMPA
;
Receptors, Muscarinic
;
Synapses
;
Synaptic Transmission
;
Visual Cortex
10.Excitatory postsynaptic potential evoked by stimulation of the ventrolateral region of the cerebellum in crucian carp Mauthner cell.
Ying-Cai ZHANG ; Shu-Hua ZHANG ; Xiao-Yi LI ; Xue-Hong TONG ; Fen YU ; Mao-Xian ZHANG
Acta Physiologica Sinica 2003;55(4):459-463
In the present experiments, the characteristics of the electrical responses to stimulation of the cerebellum in crucian carp Mauthner cell were explored with microeletrode intracellular recording technique. A composite excitatory postsynaptic potential (cerebellum-evoked EPSP) could be induced from the soma, the ventral dendrite and the proximal end of the lateral dendrite in crucian carp Mauthner cell (M-cell) on either side by stimulation of the ventrolateral region of the cerebellum. The cerebellum-evoked EPSP presented characteristics of relatively short latency (0.63+/-0.09 ms), longer duration (5.49+/-1.13 ms), graded amplitude and dependence on stimulation frequency. Stimulation of the cerebellum with higher intensity always activated the M-cell orthodromically. Multiple intracellular recordings showed that the cerebellum-evoked EPSP originated in the distal end of the ventral dendrite. The results suggest that the cerebellum-M-cell pathway is probably composed of a group of neuron chains with different numbers of synaptic relays projecting to the distal end of the ventral dendrite in order of length of the chains.
Animals
;
Carps
;
physiology
;
Cerebellum
;
physiology
;
Dendrites
;
physiology
;
Electric Stimulation
;
Excitatory Postsynaptic Potentials
;
physiology
;
Neurons
;
physiology
;
Synapses
;
physiology
;
Synaptic Transmission
;
physiology