Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Excitatory Postsynaptic Potentials”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed2005

Peptidergic contribution to posttetanic potentiation at a central synapse of aplysia.

Posttetanic potentiation (PTP)-like phenomena appear to be mediated by a variety of mechanisms. Although neuropeptides are located in a large number of neurons and many neuropeptides, like PTP, can enhance synaptic transmission, there is a paucity of studies indicating that peptides may actually participate in PTP. Here, we utilize a single central synapse in the feeding circuit of Aplysia to investigate a possible peptidergic contribution to PTP in the CNS. The cholinergic command-like interneuron, cerebral-buccal interneuron 2 (CBI-2), contains two neuropeptides, feeding circuit activating peptide (FCAP) and cerebral peptide 2 (CP2). Previous studies showed that tetanic prestimulation or repeated stimulation of CBI-2, as well as perfusion of FCAP and CP2, increase the size of the cholinergic excitatory postsynaptic potentials (EPSPs) that CBI-2 evokes in the motoneurons B61/62 and shorten the latency to initiate B61/62 firing in response to CBI-2 stimulation. We used temperature-dependent suppression of peptide release and occlusion experiments to examine the possible contribution of FCAP and CP2 to PTP at the CBI-2 to B61/62 synapse. When peptide release was suppressed, perfusion of exogenous peptides increased the size of posttetanic EPSPs. In contrast, when peptide release was not suppressed, exogenous peptides did not enhance the size of posttetanic EPSPs, thus indicating occlusion. Temperature manipulation and occlusion experiments also indicated that peptides extend PTP duration. This peptide-dependent prolongation of PTP has functional consequences in that it extends the duration of time during which the latency to initiate B61/62 firing in response to CBI-2 stimulation is shortened.

Animals↗
PubMed1998

Evidence of direct connection of corticobulbar fibers to orofacial muscles in man: electromyographic study of individual motor unit responses.

We studied corticobulbar influence on the orbicularis oris (OR) muscles by anodal and magnetic transcranial stimulation and compared it to the corticospinal influence on first dorsal interosseous muscles of healthy human volunteers. We recorded single motor unit (MU) responses and applied peristimulus time histogram (PSTH) technique to determine their properties. Peaks in the PSTHs are assumed to coincide with multiple excitatory postsynaptic potentials (EPSPs) induced at the motoneurons by corticospinal input. We found relatively small latency variation of consecutive single MU responses for both muscles. Additionally, we found a narrow initial peak in five OR MUs after anodal stimulation. This short duration indicates the presence of monosynaptic cortical projection in the lower facial motoneurons. The EPSP amplitudes, estimated on the basis of initial peak, were used as a measure of the synaptic transmission efficiency. Our results support the concept of predominantly monosynaptic transmission at the spinal level.

Adult↗
PubMed2003

Increased sensitivity to halothane but decreased sensitivity to propofol in mice lacking the N-type Ca2+ channel.

Volatile anesthetics are known to depress excitatory synaptic transmission. Inhibition of voltage-dependent Ca2+ channels is speculated to underlie this mechanism, which remains to be clarified in vivo. We examined the sensitivity to halothane in mice lacking the N-type Ca2+ channel, a major contributor of presynaptic neurotransmitter release. Sensitivity to halothane was significantly increased in the knockout mice compared with the wild-type littermates. Halothane also depressed field excitatory postsynaptic potentials recorded from the Schaffer collateral-CA1 hippocampal synapses more greatly in the knockout mice. We further examined sleep time induced by injection of propofol, an intravenous anesthetic that mainly affects inhibitory synaptic transmission. In contrast, sensitivity to propofol was significantly decreased in the knockout mice. We suggest that inhibition of the N-type Ca2+ channel underlies mechanisms of halothane anesthesia but counteracts propofol anesthesia.

Anesthetics, Inhalation↗
PubMed2002

Presynaptic modulation of GABAergic inhibition by GABA(B) receptors in the rat's inferior colliculus.

Whole-cell patch clamp recordings were made from neurons in a brain slice preparation of the inferior colliculus in 11-15-day-old rat pups. Synaptic responses were elicited by applying a current pulse to the lateral lemniscus just below the central nucleus of the inferior colliculus. To examine GABAergic inhibition in the inferior colliculus all excitatory postsynaptic potentials and glycinergic inhibitory postsynaptic potentials were blocked by bath application of their respective antagonists and the contribution of GABA(B) receptors was determined for the remaining inhibitory postsynaptic potentials. For most cells the isolated inhibitory postsynaptic potential was completely blocked by the GABA(A) receptor antagonist, bicuculline, but was unaffected by the GABA(B) receptor antagonist, phaclofen. The GABA(B) receptor agonist, baclofen (10-20 microM), decreased the amplitude of the inhibitory postsynaptic potentials. This effect was completely blocked by phaclofen. Baclofen did not increase the cell membrane conductance or alter the rate of firing produced by depolarization of the cell membrane. In contrast, muscimol, a GABA(A) receptor agonist, greatly increased membrane conductance and lowered the firing rate produced by depolarization. Our results indicate that GABAergic inhibition in the auditory midbrain can be reduced by the activation of GABA(B) receptors and suggest that the effects are presynaptic.

Animals↗
PubMed1998

Abnormal synaptic transmission in the olfactory bulb of Fyn-kinase-deficient mice.

We studied synaptic transmission in the granule cells in the olfactory bulb of the homozygous Fyn (a nonreceptor type tyrosine kinase)-deficient (fynz/fynz) and heterozygous Fyn-deficient (+/fynz) mice by using slice preparations from the olfactory bulb. Stimulation to the lateral olfactory tract and/or centrifugal fibers to the olfactory bulb evoked field excitatory postsynaptic potentials (fEPSPs) in the granule cells. In +/fynz mice, fEPSPs were augmented by bicuculline, a gamma-aminobutyric acid (GABAA) antagonist and picrotoxin, whereas fEPSPs in fynz/fynz mice were much less sensitive to bicuculline and picrotoxin. Application of D-2-amino-5-phosphonopentanoic acid had no effect but 6-cyano-7-nitroquinoxaline-2,3-dione produced almost complete block of fEPSPs in both +/fynz mice and fynz/fynz mice. (1S,3R)-1-aminocyclo-pentane-1.3-dicarboxylate, an agonist of metabotropic glutamate receptors caused a similar depression of fEPSPs in both +/fynz and fynz/fynz mice. In +/fynz mice tetanic stimulation to the lateral olfactory tract and/or centrifugal fibers induced N-methyl-D-aspartate (NMDA)-dependent long-term potentiation (LTP) of fEPSPs, whereas LTP was impaired in fynz/fynz mice. Our results demonstrate altered functions of GABAA and NMDA receptors in the olfactory system of Fyn-deficient mice.

2-Amino-5-phosphonovalerate↗
PubMed2000

A dendritic cable model for the amplification of synaptic potentials by an ensemble average of persistent sodium channels.

The persistent sodium current density (I(NaP)) at the soma measured with the 'whole-cell' patch-clamp recording method is linearized about the resting state and used as a current source along the dendritic cable (depicting the spatial distribution of voltage-dependent persistent sodium ionic channels). This procedure allows time-dependent analytical solutions to be obtained for the membrane depolarization. Computer simulated response to a dendritic current injection in the form of synaptically-induced voltage change located at a distance from the recording site in a cable with unequally distributed persistent sodium ion channel densities per unit length of cable (the so-called 'hot-spots') is used to obtain conclusions on the density and distribution of persistent sodium ion channels. It is shown that the excitatory postsynaptic potentials (EPSPs) are amplified if hot-spots of persistent sodium ion channels are spatially distributed along the dendritic cable, with the local density of I(NaP) with respect to the recording site shown to specifically increase the peak amplitude of the EPSP for a proximally placed synaptic input, while the spatial distribution of I(NaP) serves to broaden the time course of the amplified EPSP. However, in the case of a distally positioned synaptic input, both local and nonlocal densities yield an approximately identical enhancement of EPSPs in contradiction to the computer simulations performed by Lipowsky et al. [J. Neurophysiol. 76 (1996) 2181]. The results indicate that persistent sodium channels produce EPSP amplification even when their distribution is relatively sparse (i.e. , approximately 1-2% of the transient sodium channels are found in dendrites of CA1 hippocampal pyramidal neurons). This gives a strong impetus for the use of the theory as a novel approach in the investigation of synaptic integration of signals in active dendrites represented as ionic cables.

Animals↗
PubMed1999

Convergent mechanosensory input structures the firing phase of a steering motor neuron in the blowfly, Calliphora.

The first basalar muscle (B1) is 1 of 17 small steering muscles in flies that control changes in wing stroke kinematics during flight. The B1 is often tonically active, firing a single phase-locked action potential in each and every wingbeat cycle. Changes in activation phase alter the biomechanical properties of B1, which in turn cause aerodynamically relevant changes in wing motion. The phase-locked firing of the B1 motor neuron (MNB1), is thought to arise from an interaction of wingbeat-synchronous inputs from the wings and from specialized equilibrium organs called halteres that beat antiphase to the wings and function to detect angular rotation of the body during flight. We investigated how the wing and haltere inputs interact to determine the firing phase of MNB1. Our results indicate that both wing and haltere afferents make strong monosynaptic connections with MNB1, consisting of fast electrical and slow Ca(2+)-sensitive components. Although both the wing and haltere-evoked excitatory postsynaptic potentials (EPSPs) display the two components, their relative contribution is different for the two inputs. Whereas the haltere-evoked EPSP is dominated by the fast electrical component, the wing-evoked EPSP is dominated by a large chemically mediated component and displays an additional prolonged Ca(2+)-dependent component that is absent in the haltere-evoked EPSP. Both inputs display an activity-dependent fatigue affecting both electrical and Ca(2+)-sensitive components, from which the haltere synapse recovers more rapidly. The net result of these synaptic differences is that the two pathways differ significantly in their relative ability to evoke action potentials in MNB1. Although the haltere pathway displays greater temporal precision, the wing pathway is stronger, judged by its ability to entrain MNB1 within a background of haltere stimulation. We propose a model by which these physiological differences play a functional role in tuning the firing phase of MNB1 during flight. The wing input may serve primarily to set the background firing phase of MNB1, whereas the haltere input serves to transiently advance the firing phase during equilibrium reflexes.

Animals↗
PubMed2001

Attenuated LTP in hippocampal dentate gyrus neurons of mice deficient in the PAF receptor.

Platelet-activating factor (PAF), a bioactive lipid (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) derived from phospholipase A(2) and other pathways, has been implicated in neural plasticity and memory formation. Long-term potentiation (LTP) can be induced by the application of PAF and blocked by a PAF receptor (PAF-R) inhibitor in the hippocampal CA1 and dentate gyrus. To further investigate the role of PAF in synaptic plasticity, we compared LTP in dentate granule cells from hippocampal slices of adult mice deficient in the PAF-R and their age-matched wild-type littermates. Whole cell patch-clamp recordings were made in the current-clamp mode. LTP in the perforant path was induced by a high-frequency stimulation (HFS) and defined as >20% increase above baseline of the amplitude of excitatory postsynaptic potentials (EPSPs) from 26 to 30 min after HFS. HFS-induced enhancement of the EPSP amplitude was attenuated in cells from the PAF-R-deficient mice (163 +/- 14%, mean +/- SE; n = 32) when compared with that in wild-type mice (219 +/- 17%, n = 32). The incidence of LTP induction was also lower in the cells from the deficient mice (72%, 23 of 32 cells) than in the wild-type mice (91%, 29 of 32 cells). Using paired-pulse facilitation as a synaptic pathway discrimination, it appeared that there were differences in LTP magnitudes in the lateral perforant path but not in the medial perforant path between the two groups. BN52021 (5 microM), a PAF synaptosomal receptor antagonist, reduced LTP in the lateral path in the wild-type mice. However, neither BN52021, nor BN50730 (5 microM), a microsomal PAF-R antagonist, reduced LTP in the lateral perforant path in the receptor-deficient mice. These data provide evidence that PAF-R-deficient mice are a useful model to study LTP in the dentate gyrus and support the notion that PAF actively participates in hippocampal synaptic plasticity.

Animals↗
PubMed2006

Fractalkine/CX3CL1 depresses central synaptic transmission in mouse hippocampal slices.

This work reports the effect of chemokine fractalkine/CX3CL1, an endogenous small peptide highly expressed in the central nervous system, on evoked synaptic responses investigated in mouse CA1 stratum radiatum using an electrophysiological approach. We report that in acute mouse hippocampal slices, superfusion of CX3CL1 resulted in a reversible depression of the field excitatory postsynaptic potential (fEPSP) which developed within few seconds, increased for up to 10 min of application and disappeared within 30 min after the end of CX3CL1 treatment. We also show that CX3CL1-induced synaptic depression is (i) dose-dependent with IC50 and nH values of 0.7 nM and 1, respectively, (ii) not associated with a change in paired-pulse facilitation, (iii) mediated through CX3CL1 receptor (CX3CR1), being absent in CX3CR1-/- mice and inhibited in wild-type mice by a specific blocking antibody, and (iv) occluded by the induction of homosynaptic long-term depression (LTD). We conclude that CX3CL1 is a potent neuromodulator of the evoked excitatory synaptic transmission, sharing common mechanisms with LTD.

Animals↗
PubMed2003

Widely integrative properties of layer 5 pyramidal cells support a role for processing of extralaminar synaptic inputs in rat neocortex.

We have compared the length, strength, conduction velocity and divergence of horizontal connections onto layers 2/3 and 5 neurons in slices of rat primary somatosensory neocortex. Slices were cut along laminar borders to eliminate most vertical connections, and excitatory postsynaptic potentials (EPSPs) were recorded from pyramidal cells in adjacent uncut tissue. When electric stimuli were delivered within the same layer as the recorded cell, EPSPs could be evoked up to 2000 microm away for both layers 2/3 and 5 pyramids. Estimates of horizontal axonal conduction velocities ( approximately 0.4 m/s) and the thresholds for activation also did not differ between layers. However, layers 2/3 cells rarely responded to stimuli delivered to isolated deeper layers, while layer 5 neurons were often excited by horizontal inputs from isolated layers 2/3 and 4.

Animals↗
PubMed2000

Primary afferent synaptic responses recorded from trigeminal caudal neurons in a mandibular nerve-brainstem preparation of neonatal rats.

1. Whole-cell patch-clamp recordings were made from the neurons in the superficial trigeminal caudal nucleus (substantia gelatinosa) visually identified in a parasagittal brainstem slice of neonatal rat with the mandibular nerve attached. 2. Stimulation of the mandibular nerve at 0.03 Hz evoked compound excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in trigeminal caudal neurons. When stimulated at higher frequency (> 0.5 Hz), compound synaptic responses were largely attenuated and a small component remained. This component had a monosynaptic nature, following high-frequency stimulation (33-50 Hz) with a stable synaptic latency. 3. The N-methyl-D-aspartate (NMDA) receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5, 50 microM) largely attenuated the slow polysynaptic EPSCs. The AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) largely attenuated monosynaptic EPSCs, but only weakly attenuated slow polysynaptic EPSCs. Simultaneous application of CNQX and D-AP5 completely abolished EPSCs. The monosynaptic EPSCs isolated by repetitive stimulation had both NMDA and non-NMDA components. 4. Monosynaptic EPSCs having high threshold had a relatively long latency. During repetitive stimulation (0.5-5.0 Hz), EPSCs having high threshold and long latency underwent a stepwise potentiation in an activity-dependent manner. The conduction velocity estimated for these EPSCs fell into the range of C-fibres. The activity-dependent potentiation was observed for both non-NMDA and NMDA EPSCs and was accompanied by a significant decrease in the coefficient of variation of EPSC amplitude. 5. We suggest that the activity-dependent potentiation of EPSCs is induced presynaptically and that it may underlie the wind-up phenomenon, an activity-dependent hyperexcitability of the primary afferent C-fibres.

2-Amino-5-phosphonovalerate↗
PubMed2004

Synaptic enhancement induced through callosal pathways in cat association cortex.

The corpus callosum plays a major role in synchronizing neocortical activities in the two hemispheres. We investigated the changes in callosally elicited excitatory postsynaptic potentials (EPSPs) of neurons from cortical association areas 5 and 7 of cats under barbiturate or ketamine-xylazine anesthesia. Single pulses to callosal pathway evoked control EPSPs; pulse-trains were subsequently applied at different frequencies to homotopic sites in the contralateral cortex, as conditioning stimulation; thereafter, the single pulses were applied again to test changes in synaptic responsiveness by comparing the amplitudes of control and conditioned EPSPs. In 41 of 42 neurons recorded under barbiturate anesthesia, all frequencies of conditioning callosal stimuli induced short-term (5-30 min) enhancement of test EPSPs elicited by single stimuli. Neurons tested with successive conditioning pulse-trains at different frequencies displayed stronger enhancement with high-frequency (40-100 Hz) than with low-frequency (10-20 Hz) rhythmic pulse-trains; >100 Hz, the potentiation saturated. In a neuronal sample, microdialysis of an N-methyl-D-aspartate (NMDA) receptor blocker in barbiturate-treated cats suppressed this potentiation, and potentiation of callosally evoked EPSPs was not detected in neurons recorded under ketamine-xylazine anesthesia, thus indicating that EPSPs' potentiation implicates, at least partially, NMDA receptors. These data suggest that callosal activities occurring within low-frequency and fast-frequency oscillations play a role in cortical synaptic plasticity.

2-Amino-5-phosphonovalerate↗
PubMed2005

Adenosine A2A receptors and metabotropic glutamate 5 receptors are co-localized and functionally interact in the hippocampus: a possible key mechanism in the modulation of N-methyl-D-aspartate effects.

Hippocampal metabotropic glutamate 5 receptors (mGlu5Rs) regulate both physiological and pathological responses to glutamate. Because mGlu5R activation enhances NMDA-mediated effects, and given the role played by NMDA receptors in synaptic plasticity and excitotoxicity, modulating mGlu5R may influence both the physiological and the pathological effects elicited by NMDA receptor stimulation. We evaluated whether adenosine A2A receptors (A(2A)Rs) modulated mGlu5R-dependent effects in the hippocampus, as they do in the striatum. Co-application of the A(2A)R agonist CGS 21680 with the mGlu5R agonist (RS)-2-chloro-s-hydroxyphenylglycine(CHPG) synergistically reduced field excitatory postsynaptic potentials in the CA1 area of rat hippocampal slices. Endogenous tone at A(2A)Rs seemed to be required to enable mGlu5R-mediated effects, as the ability of CHPG to potentiate NMDA effects was antagonized by the selective A(2A)R antagonist ZM 241385 in rat hippocampal slices and cultured hippocampal neurons, and abolished in the hippocampus of A(2A)R knockout mice. Evidence for the interaction between A(2A)Rs and mGlu5Rs was further strengthened by demonstrating their co-localization in hippocampal synapses. This is the first evidence showing that hippocampal A(2A)Rs and mGlu5Rs are co-located and act synergistically, and that A(2A)Rs play a permissive role in mGlu5R receptor-mediated potentiation of NMDA effects in the hippocampus.

Adenosine↗
PubMed1999

Intracortical excitation of spiny neurons in layer 4 of cat striate cortex in vitro.

Recordings were made from pairs of neurons in cat striate visual cortex in vitro to study the AMPA-channel-mediated components of intracortical excitatory synaptic connections between layer 4 spiny neurons and between layer 6 and layer 4 spiny neurons. Forty-six of the 72 cells recorded were identified morphologically. They consisted of spiny stellate and pyramidal cells in layer 4, and pyramidal cells in layer 6. Connections between layer 4 excitatory cells involve excitatory postsynaptic potentials (EPSPs) averaging 949 microV, with an average coefficient of variation of 0.21 (n = 30). The synapses operate at very high release probabilities (0.69-0.98). With repetitive stimulation these EPSPs show varying degrees of depression, largely mediated by presynaptic changes in release probability. Four pairs of layer 4 cells were reciprocally connected. The connections from layer 6 to layer 4 involve smaller, more variable EPSPs, with an average amplitude of 214 microV, and average coefficient of variation 0.72 (n = 7). These synapses operate at moderately high release probabilities (0.37-0.56). They show facilitation with repetitive stimulation, mediated largely by presynaptic changes in release probability. One excitatory connection from a layer 4 neuron to a layer 6 pyramidal cell was also detected. Thus, layer 4 spiny neurons receive effective excitation from two intracortical sources that have different synaptic dynamics and are likely to contribute significantly to the temporal properties of these cells in vivo.

Animals↗
PubMed1959

The function of the proximal synapses of the squid stellate ganglion.

In the oxygenated excised squid (Loligo pealii) stellate ganglion preparation one can produce excitation of the stellar giant axons by stimulating the second largest (accessory fiber, Young, 1939) or other smaller preganglionic giant axons. Impulse transmission is believed to occur at the proximal synapses of the stellar giant axons rather than the distal (giant) synapses which are excited by the largest giant preaxon. Proximal synaptic transmission is more readily depressed by hypoxia and can be fatigued independently of, and with fewer impulses than, the giant synapses. Intracellular recording from the last stellar axon at its inflection in the ganglion reveals both proximal and distal excitatory postsynaptic potentials EPSP's). The synaptic delay, temporal form of the EPSP, and depolarization for spike initiation were similar for both synapses. If the proximal EPSP occurs shortly after excitation by the giant synapse it reduces the undershoot and adds to the falling phase of the spike. If it occurs later it can produce a second spike. Parallel results were obtained when the proximal EPSP's arrived earlier than the EPSP of the giant synapse. In fatigued preparations it was possible to sum distal and proximal or two proximal EPSP's and achieve spike excitation.

Animals↗
PubMed1999

Serotonin receptor subtypes that depolarize guinea pig inferior mesenteric ganglion neurons.

Our previous studies indicated that serotonin (5-HT) depolarized a majority of guinea pig inferior mesenteric ganglion (IMG) neurons and may be another transmitter for the noncholinergic late slow excitatory postsynaptic potential (ls-EPSP) in the IMG. However, the subtypes of 5-HT receptor mediating these responses have not yet been identified. Using intracellular recording, we examined the effect of 5-HT receptor antagonists with specificity to various 5-HT receptor subtypes on the 5-HT-mediated depolarization and ls-EPSP in IMG neurons in vitro. Cyproheptadine, a 5-HT(1/2) receptor antagonist, reversibly inhibited the slow, but not the fast, depolarization and ls-EPSP in the 5-HT-sensitive neurons. Both mianserin and spiperone, 5-HT(2) and 5-HT(1A) receptor antagonists, did not significantly alter either the fast or slow depolarizing responses or the ls-EPSP. The 5-HT(3) receptor antagonist MDL 72222 (Bemesetron) completely inhibited the fast depolarization with little diminution of the slow depolarization and ls-EPSP. Superfusion of putative 5-HT(1P) receptor antagonist, BRL 24924 (Renzapride), reversibly attenuated both the depolarization and ls-EPSP. However, 5-HT-insensitive neurons with ls-EPSP were found to be insensitive to both cyproheptadine and BRL 24924. In most 5-HT-sensitive neurons, the 5-HT(3) receptor agonist, 2-methyl-5-HT, and the selective 5-HT(1P) agonist, MCPP or 5-OHIP, evoked a fast and a slow depolarization in 55.6 and 71.4% of the neurons, respectively, without a significant effect on the membrane potential in 85.7 and 100% of the 5-HT-insensitive neurons. In 5-HT-sensitive neurons, MDL 72222 reversibly abolished the fast depolarization induced by 2-methyl-5-HT; BRL 24924 significantly inhibited the slow depolarization induced by MCPP or 5-OHIP, but not by SP. Prolonged superfusion of 5-HT-sensitive neurons with MCPP abolished the evoked ls-EPSP without inhibition of action potential. These results suggest that the fast and slow depolarizations in these neurons are mediated by 5-HT(3) and 5-HT(1P) receptor subtypes, respectively. The latter may also mediate the ls-EPSP in 5-HT-sensitive neurons.

Animals↗
PubMed2004

Repeated electroconvulsive stimulation impairs long-term depression in the neostriatum.

BACKGROUND: Increasing and consistent findings of structural and functional abnormalities in patients with mood disorders demonstrate a clear involvement of the neostriatum. Therefore, the beneficial effect of electroconvulsive stimulation (ECS) treatment of acute state of mood disorder may relate to changes in striatal synaptic plasticity. METHODS: We studied the effect of ECS treatment on the reported long-term depression (LTD) of synaptic excitatory afferents to striatal medium spiny neurons. Stimulation of the white matter between the cortex and the striatum elicited excitatory postsynaptic potentials (EPSPs) in medium spiny neurons in rat corticostriatal slices while recording using the whole-cell patch-clamp technique. RESULTS: The EPSPs evoked in striatal neurons undergo LTD with repeated stimulation trains, and LTD of this pathway is impaired in rats after ECS treatment for 1 week, similar to what is reported in chronic lithium treatment. Electroconvulsive stimulation did not affect intrinsic membrane properties or the occurrence of spontaneous EPSCs. Dose-dependent inhibition of the EPSPs by a nonselective agonist of metabotropic glutamate receptor did not change in rats after ECS treatment. CONCLUSIONS: Our data suggest that the effectiveness of electroconvulsive therapy in mood disorders may be a consequence of LTD impairment of excitatory cortical afferents to striatal projecting neurons.

Animals↗
PubMed2004

Pharmacological manipulation of mGlu2 receptors influences cognitive performance in the rodent.

Atrophy of the medial temporal lobes, including the glutamatergic cortical-hippocampal circuitry, is an early event in Alzheimer's disease (AD) and probably contributes to the characteristic short-term mnemonic decline. Pharmacological strategies directly targeted to ameliorating this functional decline may represent a novel approach for the symptomatic treatment of AD. Presynaptic group II metabotropic glutamate receptors (i.e. mGlu2 and mGlu3) exert a powerful modulatory influence on the function of these pathways, in particular the perforant pathway. Using a combination of mGlu2 receptor knockout mice and the group II agonist LY354740, we show that activation of mGlu2 receptors produces a cognitive impairment, i.e. a delay-dependent deficit in delayed matching and non-matching to position, and impaired spatial learning in a Morris water maze. Conversely, a group II antagonist, LY341495, improved acquisition of spatial learning. LY354740 potently reduced field excitatory postsynaptic potentials in hippocampal slices from wild type but not mGlu2 receptor knockout mice. Taken together, these results suggest that activation of mGlu2 receptors evokes a powerful inhibitory effect on hippocampal synaptic transmission and mGlu2 agonists produce a cognitive deficit consistent with this change. Conversely, mGlu2 receptor antagonists may improve certain aspects of cognition and thus represent a novel approach for the symptomatic treatment of AD.

Amino Acids↗