SEARCH · PubMed Health

Results for “Long-Term Synaptic Depression”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 289 records · Page 16Linked to original sources

PubMed1994

Pathway specificity of noradrenergic plasticity in the dentate gyrus.

Previous experiments have described highly specific effects of noradrenergic agonists on synaptic transmission in the dentate gyrus (DG). For example, perfusion of hippocampal slices with the beta-noradrenergic agonist isoproterenol induces a long-lasting potentiation (LLP) of extracellularly recorded responses following stimulation of the medial perforant path (PP), and long-lasting depression (LLD) of responses evoked by stimulation of the lateral PP (Dahl D, Sarvey JM, 1989, Proc Natl Acad Sci USA 86:4776-4780). To examine the possible interactions of LLP, LLD, and long-term potentiation induced by tetanic stimulation (LTP), the authors recorded extracellular field potentials evoked in the DG by stimulation of the lateral or medial perforant path following LTP and LLP or LLD, invoked in different orders. After establishment of LLP or LLD by bath application of isoproterenol, subsequent tetanization of the respective afferents resulted in additional potentiation of the medial PP-evoked response and return of the lateral PP-evoked response to baseline levels. In other slices, application of isoproterenol after establishment of LTP resulted in further potentiation of medial PP-evoked responses but no change in the potentiated response evoked by lateral PP stimulation. Thus the pathway specificity was maintained irrespective of the history of previous potentiation or depression. Experiments using the specific beta 1 antagonist metoprolol further confirmed pathway specificity. Perfusion with 20 microM of metoprolol appeared to reduce LTP evoked by stimulation of the medial but not lateral PP. In a subsequent experiment, metoprolol in the absence of tetanization produced LLD of the medial PP-evoked response and LLP of the lateral PP-evoked response, opposite to the effects of ISO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Long-term potentiation of nicotinic transmission by a heterosynaptic mechanism in the stellate ganglion of the cat.

1. In the anesthetized, scopolamine-treated cat, the compound action potential (CAP) evoked by a single supramaximal shock to the third thoracic white ramus (T3WR) was recorded in the inferior cardiac nerve (ICN). The CAP was depressed in a dose-dependent manner by the intravenous administration of the nicotinic antagonist hexamethonium (C6). 2. During steady intravenous infusion of C6, which reduced the amplitude of the CAP by 80-90%, a short train of stimuli (few seconds, 10-40 Hz) to the sympathetic trunk just below T4WR potentiated the CAP for periods of tens of minutes to 1-2 h (heterosynaptic long-term potentiation, LTP). An LTP of similar time course was obtained when both train and single shock were applied to T3WR (homosynaptic LTP). Magnitude and duration of the heterosynaptic LTP were dependent on number, frequency, and intensity of the stimuli. No LTP was produced by a train to the ICN. Heterosynaptic LTP was also observed in the absence of C6. Because of the limited subliminal fringe of the test input under this condition, the LTP was of small magnitude. Heterosynaptic LTP also of the heart rate (HR) response to a test stimulus was observed after a conditioning train. 3. The conditioning train produced a displacement to the right of the dose-response curve for C6. The intravenous dose of C6 required for 50% attenuation of the test CAP increased from 0.84 +/- 0.15 (SE) mg/kg pretrain to 2.56 +/- 0.46 mg/kg posttrain (n = 5, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1994

Developmental shift from long-term depression to long-term potentiation at the mossy fibre synapses in the rat hippocampus.

During development, in the CA1 hippocampal region, long-term potentiation (LTP) starts appearing at postnatal (P) day 7 and reaches its maximal expression towards the end of the second postnatal week. However, LTP is often preceded by long-term depression (LTD), an activity-dependent and long-lasting reduction of synaptic strength. LTD can be induced by sustained, low-frequency stimulation of the afferent pathway and is dependent on activation of N-methyl-D-aspartate (NMDA) receptors. We report here that, in the CA3 hippocampal region, during a critical period of postnatal development, between P6 and P14, a high-frequency stimulation train (100 Hz, 1 s) to the mossy fibres in the presence of the NMDA receptor antagonist (+)-3-(2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid (CPP; 20 microM) induced LTD. The depression of the amplitude of the field excitatory postsynaptic potential (EPSP) was 28 +/- 7% (n = 21). This form of LTD was NMDA-independent and synapse-specific. When a tetanus was applied in the presence of CPP and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 microM), which blocked the field EPSP, it failed to induce LTD upon washout of CNQX. LTD was probably postsynaptic in origin since it did not affect paired-pulse facilitation. A rise in extracellular calcium concentration (from 2 to 4 mM) produced LTP instead of LTD. At the end of the second postnatal week, the same high-frequency stimulation train to the mossy fibres induced LTP as in adult neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Changes in sympathetic neurotransmission and adrenergic control of cardiac contractility during 1,3-dipropyl-8-sulfophenylxanthine-induced hypertension.

We have explored the hypothesis that systemic hypertension induced by long-term treatment with the purinoceptor antagonist 1,3-dipropyl-8-sulfophenylxanthine (DPSPX) might be associated with functional modifications of the adrenergic mechanisms of control of cardiac performance comparable to those described in other models of hypertension. Seven days continuous i.p. infusion of rats with DPSPX (30 micrograms/kg/hr) significantly increased systolic blood pressure. When sympathetic neurotransmission was evaluated via electrical field stimulation of atrial tissue, contractile responses were significantly reduced in hypertensive animals compared to controls. Similarly, contractile responses to exogenous norepinephrine were attenuated in tissue from hypertensive animals, thus suggesting that DPSPX treatment affects cardiac sympathetic neurotransmission via postjunctional rather than prejunctional changes. Inotropic responses of ventricular myocardium to both alpha- and beta-adrenoceptor stimulation were also significantly reduced in DPSPX-treated tissue. The responsiveness of atrial and ventricular myocardium to adenosine was unaffected by DPSPX treatment. The present study indicates that DPSPX-induced hypertension is associated with altered adrenergic regulation of the cardiac function that results in reduced inotropic responses of both atrial and ventricular myocardium to endogenous norepinephrine, as well as to adrenoceptor agonists applied exogenously. These alterations are comparable to those described in other models of genetic or induced hypertension, thus supporting the view that purinergic mechanisms may contribute to the onset and development of systemic hypertension.

Adenosine↗

PubMed1990

Striatal preprotachykinin and preproenkephalin mRNA levels and the levels of nigral substance P and pallidal Met5-enkephalin depend on corticostriatal axons that use the excitatory amino acid neurotransmitters aspartate and glutamate: quantitative radioimmunocytochemical and in situ hybridization evidence.

Because excitatory amino acid (EAA) neurotransmission has been implicated in long-term postsynaptic events, we conducted an initial study to determine whether or not the EAA-utilizing corticostriatal projection might influence peptide biosynthesis in neurons of the rat's basal ganglia. The content of EAAs in the caudatoputamen was reduced by frontal cortical ablation or by chronic intracerebroventricular infusion of methionine sulfoximine (MS). At 7 days following cortical ablation striatal Asp and Glu were reduced by 15% and 24%, respectively, while MS infusion (24 micrograms/day) for 7 days reduced synaptosomal levels of Asp by 61% and Glu by 48%. With either treatment, quantitative radioimmunocytochemistry revealed that substance P (SP) in the substantia nigra was increased by approximately 38%, while Met5-enkephalin (ME) in the globus pallidus was not changed. In situ hybridization with oligonucleotide probes revealed changes in the rostral striatum of preprotachykinin (PPT) and preproenkephalin (PPE) mRNA levels: cortical ablation reduced PPT mRNA by 17% and PPE mRNA by 20% dorsally, while it increased PPE mRNA (but not PPT mRNA) by 23% ventrally. Likewise, the infusion of MS decreased PPT (32%) and PPE mRNA (28%) dorsally, and increased PPE mRNA (50%) ventrally. In addition to the 7 day time point, the same measurements of EAAs, peptides and mRNAs were made at 14, 21 and 28 days after cortical excisions. At 14 days, the level of striatal Asp had returned to control value, but Glu remained depressed by 21%; nigral SP remained increased by 24%, and pallidal ME decreased by 15%. PPT and PPE mRNA remained depressed dorsally by 15% and 25%, respectively, while the increase in PPE mRNA noted ventrally at 7 days had returned to control values by 14 days. With the exception of Glu, which remained depressed by 18% at 21 and 28 days, all other values had returned to control levels by 21 days. The results indicate that a large reduction in EAA neurotransmission can influence differentially the steady-state levels of neuropeptides in striatal neurons and this change is brought about, at least in part, by an alteration in gene transcription.

Animals↗

PubMed1995

On the linkage between AMPA and NMDA receptor-mediated EPSPs in homosynaptic long-term depression in the hippocampal CA1 region of young rats.

Homosynaptic long-term depression (LTD) was studied in hippocampal slices from 12-18-d-old rats using field EPSP recording in the apical dendritic layer of CA1 pyramidal cells. Independent estimates of the alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and the N-methyl-D-aspartic acid (NMDA) receptor-mediated components of the field EPSP were obtained in parallel using early and late measurements of a dual-component EPSP in a low-magnesium solution. LTD was induced by low-frequency stimulation (LFS; 2 Hz for 10 min), resulting in equal relative changes of the AMPA and NMDA receptor-mediated components. Under conditions when the AMPA receptor-mediated component was fully blocked, a similarly sized LTD was observed for the pure NMDA receptor-mediated EPSP (measured as initial slope or peak amplitude). Equal changes in AMPA and NMDA receptor-mediated components occurred also upon application of the adenosine agonist N6-cyclohexyladenosine (CHA), known to act by decreasing transmitter release. On the other hand, LTD was found to interact in a multiplicative manner with the presynaptic release changes induced by CHA and by paired-pulse facilitation. The induction of the LTDs of both AMPA and NMDA receptor-mediated EPSPs was blocked by the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid and by the phosphatase inhibitor okadaic acid. Partial blockade of LTD by okadaic acid resulted in equal partial blockade of the LTDs of the AMPA and NMDA receptor-mediated components. On the other hand, the L-type calcium channel blocker nifedipine, the metabotropic glutamate receptor antagonist (RS)-alpha-methyl-4-carboxyphenylglycine, the nitric oxide synthase inhibitor N omega-nitro-L-arginine, and the heme oxygenase inhibitor protoporphyrin IX zinc(II) had no effect on LTD of either the AMPA or the NMDA receptor-mediated component. These results of equal changes of AMPA and NMDA receptor-mediated components of the field EPSP in association with LTD, and the consistent parallelism of effects or noneffects on these components by various receptor antagonists and enzyme inhibitors, seem more easily explained by a presynaptic locus for LTD than by a postsynaptic one.

Animals↗

PubMed1994

Long-lasting potentiation and depression by novel isoproterenol and cholecystokinin 8-S interactions in the dentate gyrus.

In the in vitro hippocampal slice, novel interactions of a beta-adrenergic agonist (l-isoproterenol) and neuropeptide (cholecystokinin 8-S) differentially produce long-lasting modifications in the dentate gyrus. When co-applied, a low concentration of l-isoproterenol (50-75 nM) and cholecystokinin 8-S (1.0 microM) produce long-lasting depression of evoked action potentials (i.e., population spikes). In contrast, the same concentration of l-isoproterenol followed by a 30-min wash with artificial cerebrospinal fluid and application of cholecystokinin 8-S produces long-lasting potentiation of evoked action potentials. In neither condition are there corresponding modifications of excitatory post-synaptic potentials. These results indicate that l-isoproterenol and cholecystokinin 8-S temporally interact to differentially produce depression or potentiation of granule cell-activation In contrast to long-lasting modifications produced by continuous application of 1.0 microM l-iso-proterenol, in which both evoked action potentials and excitatory post-synaptic potentials are affected, the present novel paradigm may modify an extra-synaptic locus.

Animals↗

PubMed1984

Influences of sinusoidal electric fields on excitability in the rat hippocampal slice.

The influence of extracellular sinusoidal electric fields on the amplitude of population spikes evoked by single test pulses in excitatory pathways to CA1 pyramidal neurons was studied in rat hippocampal slices. The fields in the tissue were of the order of EEG gradients. Stimulation at 5 Hz, a frequency representative of hippocampal theta activity, was compared with 60 Hz, which is often used in kindling procedures. Brief stimulation (5-30 s) with both 5 and 60 Hz fields (20-70 mV/cmp-p in the perfusing solution) often produced a long-term increase (longer than 10 min) of the population spike. Fields at 60 Hz, but not at 5 Hz, also induced short-term depression (1-6 min) or transient post-field excitation (15-30 s). Prolonged stimulation (3 min) emphasized this frequency dependent response: fields at 5 Hz induced long-lasting potentiation while fields at 60 Hz always resulted in progressive depression persisting for a few minutes after the end of stimulation. These effects appeared as a global response of CA1 neurons. Antidromic responses studied during blockade of synaptic transmission (0.2 mM Ca2+, 4 mM Mg2+) were depressed during and following 3 min field stimulation at either frequency, which could reflect failing calcium mechanisms in the tissue. The field influence on the potential evoked by synaptic or antidromic stimulation was independent of the phase of the sine wave at which the test pulse was delivered, arguing against a direct polarization of the cell membrane by the fields. The experimental evidence suggests a functional role for EEG-like fields in hippocampal excitability.

Animals↗

PubMed1985

Functional plasticity in two afferent systems of the granule cells in the rat dentate area: frequency-related changes, long-term potentiation and heterosynaptic depression.

Monosynaptic evoked field potentials (MEFP) were recorded in the dentate gyrus of male Wistar rats upon stimulation of either the perforant path or the commissural system. While the perforant path potential exhibited in acute experiments a clear reversal point of the field excitatory postsynaptic potential (EPSP) and population spike when protruding the registration electrode from the hippocampal fissura to the hilus of the dentate gyrus, the simultaneously registered commissural potential elicited by stimulation of the contralateral hilus showed no reversal of the negative monophasic wave but merely an amplitude maximum 40 microns above the reversal point of the perforant path potential. Frequency-related changes of the MEFPs during short tetanic stimulation with 15 Hz both in acute and chronic experiments, revealed differences in the properties of the input systems in that the commissural potential exhibited a clear frequency potentiation whereas the perforant path potential showed frequency depression. Pronounced long-term potentiation of the perforant path potential induced by 4 trains of tetanizing stimuli and lasting up to 72 h was accompanied by a long-term heterosynaptic depression of the commissural potential for up to 7 days after tetanization. Both the different frequency-related changes of the inputs and the extremely long duration of the heterosynaptic depression are discussed with respect to their proposed functions in the mechanisms of functional plasticity.

Animals↗

PubMed1988

Activation of protein kinase C induces a long-term depression of glutamate sensitivity of cerebellar Purkinje cells. An in vitro study.

In immature rat cerebellar slices in vitro, a long term depression (LTD) of the responses of Purkinje cells (PCs) to L-glutamate (Glu) was achieved in 30% of the recorded cells by simultaneous stimulation of the neurones by Glu and by climbing fibres (CFs). This effect was not observed for L-aspartate (Asp)-induced responses. Similarly, selective LTD of Glu-induced responses was obtained in 22% of the cells by pairing Glu applications with direct stimulation of the cells which elicited calcium spikes in these neurones. Finally, bath application of phorbol esters also induced a selective LTD of Glu-induced responses in all cells tested. These results suggest that protein kinase C is involved in cerebellar synaptic plasticity.

Animals↗

PubMed1990

Long-term potentiation in rat hippocampus is inhibited by low concentrations of ethanol.

Acute ethanol ingestion impairs memory in humans at concentrations associated with mild intoxication. A possible neurophysiological correlate of this effect is the suppression by ethanol of long-tem potentiation (LTP), a persistent increase in synaptic efficiency which has been proposed as a substrate for memory. However, in previous studies ethanol has been shown to impair LTP only at very high concentrations, near the lethal level in humans. We now report that ethanol can significantly reduce LTP in rat hippocampus at concentrations as low as 5 mM, a level attainable following ingestion of a single alcoholic drink. We also demonstrate that the potency of ethanol in depressing LTP correlates well with its potency in inhibiting the response to N-methyl-D-aspartate, an agonist at the glutamate receptors implicated in LTP induction. The influence of low ethanol concentrations on LTP may contribute to the memory impairment associated with its use in humans.

Animals↗

PubMed1994

Serotonin controls the magnitude of LTP induced by theta bursts via an action on NMDA-receptor-mediated responses.

The present studies examined the inhibitory effects of serotonin (5-HT) on LTP in the context of the theta burst stimulation paradigm and its known relationship to the induction chemistries of LTP. Comparisons were made between the effects of various dosages of 5-HT on: (i) the extent to which the second member of a pair of theta bursts was facilitated over the first member of the pair; and (ii) the degree of LTP produced by the paired bursts. Both LTP and burst facilitation were affected in a graded manner by the drug: at high concentrations LTP was completely blocked and burst enhancement was minimal, at lower dosages LTP stabilized at a reduced level while burst responses showed substantial but still impaired facilitation. The competitive antagonist AP-5 was then used to test if 5-HT blocked the NMDA receptor mediated synaptic currents which normally occur during the facilitated burst responses. AP-5 had no effect on the size of burst responses in slices pre-treated with 5-HT indicating that serotonin suppressed the activation of the NMDA receptors by theta stimulation. Serotonin depressed the facilitation of burst responses in slices pre-treated with AP-5 indicating that it also reduces the enhanced AMPA receptor mediated currents that occur during theta pattern stimulation. These results are discussed in terms of the known effects of serotonin on hippocampal physiology and how these might interact with the machinery whereby theta stimulation activates NMDA receptor mediated currents.

2-Amino-5-phosphonovalerate↗

PubMed1992

Long-term potentiation induced by patterned stimulation of the commissural pathway to hippocampal CA1 region in freely moving rats.

In urethane-anesthetized rats, stimulation of the contralateral hippocampal CA1 region resulted in activation of the homotopic CA1 region. Current-source-density analysis revealed that both basal and apical dendrites were activated. However, alveolar and stratum oriens stimulation in CA1 gave about equal peak excitation of the basal and apical dendrites while CA1 stratum radiatum/moleculare and CA3c stimulation gave stronger apical than basal dendritic excitation. In chronically implanted and freely moving rats, tetanic patterned stimulation of the contralateral CA1, irrespective of depth, resulted in a robust long-term potentiation of the ipsilateral CA1 basal dendritic synapse. The population basal dendritic excitatory postsynaptic potential was initially potentiated to greater than 200% of the baseline and decayed with a 3 h time constant; it lasted at least two days. Patterned stimulation of the commissural inputs at 2 x threshold stimulus intensity seldom potentiated the apical dendritic synapse in CA1; rather, long-term depression was sometimes observed. After tetanic stimulations at 3 x threshold, a small potentiation of the apical dendritic excitation was seen in about half of the experiments. The average apical dendritic potentiation peaked at about 25% and persisted to at least one day. This study provides original evidence that the properties of long-term potentiation are different at the commissural basal dendritic and apical dendritic synapses in CA1 of the behaving rat. Basal dendritic potentiation is low-threshold, high-amplitude and decayed rapidly in the first 3 h. Apical dendritic potentiation is high-threshold, low-amplitude and not rapidly decaying. A long-lasting enhancement of synaptic transmission has been postulated as a physiological correlate of memory. This paper reports properties of this synaptic enhancement for two different types of synapses on the same cells in the behaving animal. The basal dendritic synapse on hippocampal pyramidal cells readily increased their efficacy, up to at least two days, after a brief, patterned stimulation. In the same preparation, it was difficult to obtain a long-lasting increase in the apical dendritic excitation, in contrast to studies on isolated hippocampal slices in vitro.

Animals↗

PubMed1989

Effect of volatile anesthetics on synaptic transmission in the rat hippocampus.

The synaptic effects of halothane, isoflurane, and enflurane were examined in the rat hippocampus in vivo and compared with the effects of ketamine and urethane. Actions of the agents on excitatory amino acid-mediated neurotransmission were studied by observing evoked responses and long-term potentiation in the stratum pyramidale of CA1 with stimulation of the contralateral CA3 region. Long-term potentiation is a long-lasting increase in synaptic efficacy, which follows a brief stimulus train. It has been shown to be established through activation of the NMDA subclass of excitatory amino acid receptors and is thought to be involved in memory processing. Volatile anesthetics had no effect on evoked excitatory responses or on long-term potentiation. Actions of the anesthetics on inhibitory processes in the hippocampus were studied by pairing stimuli at a range of interpulse intervals. The first stimulus activated inhibitory processes that caused the response to the second stimulus to be smaller than the initial response, a phenomenon termed paired pulse depression. Paired pulse depression was significantly prolonged by the volatile anesthetics compared with that under urethane or ketamine. These results indicate that the mechanism of action of the volatile anesthetics at the hippocampal CA1 synapse does not involve amino acid-mediated excitation but does involve enhancement of inhibition.

Animals↗

PubMed1990

Hippocampal synaptic plasticity and NMDA receptors: a role in information storage?

There has recently been renewed interest in the idea that alterations in synaptic efficacy may be the neural basis of information storage. Particular attention has been focused upon long-term potentiation (LTP), a long-lasting, but experimentally induced synaptic change whose physiological properties point to it being a candidate memory mechanism. However, considerations of storage capacity and the possibility of concomitant activity-dependent synaptic depression make it unlikely that individual learning experiences will give rise to gross changes in field potentials similar to those that occur in LTP, even if learning and LTP utilize common neural mechanisms. One way of investigating the functional significance of LTP is to use selective antagonists of those excitatory amino acid receptors whose activation is essential for its induction. This paper discusses various design requirements for such experiments and reviews work indicating that the N-methyl-D-aspartate receptor antagonist AP5 causes a behaviourally selective learning impairment having certain common features to the behavioural profile seen after hippocampal lesions. Two new studies are described whose results show that AP5 has no effect upon the retrieval of previously established memories, and that the dose-response profile of the impairment of spatial learning occurs across a range of extracellular concentrations in hippocampus for which receptor selectivity exists. These experiments show that activation of NMDA receptors is essential for certain kinds of learning.

Animals↗

PubMed1985

Long-term changes in hippocampal physiology and learning ability of rats after intrahippocampal tetanus toxin.

A chronic epileptic syndrome can be induced by injecting minute doses of tetanus toxin into rat hippocampi. This causes intermittent epileptic fits over a period of 2-4 weeks, after which the fits cease, and the electroencephalogram (e.e.g.) appears to return to normal over the following 2-3 weeks. However, once they have recovered from the seizures, the rats exhibit a remarkably persistent impairment of learning and memory, which is the subject of the present study. Learning ability was assessed using a radial arm maze task, in which the rats had to visit each of eight arms for a food reward. The toxin-injected rats learnt this task more slowly than control-injected. Evoked potentials from the CA3 pyramidal cells were recorded in terminal experiments under halothane anaesthesia. Long term potentiation of the post-synaptic response to the commissural pathway from the contralateral hippocampus appeared to be unaffected by the previous toxin treatment, at least over periods of up to 5 h. The toxin-injected group differed from the control in having consistently smaller post-synaptic population spikes in their evoked responses, so that stimuli were less effective in exciting the post-synaptic neurones. This applied both to the contralateral commissural input, and to the ipsilateral mossy fibre input. No differences were found between the toxin and control groups in the size of the antidromic population spike in the commissural response, or in the population excitatory post-synaptic potential (e.p.s.p.) for either input. Thus the depressed output from CA3 pyramidal cells cannot be explained either by a loss of these neurones (confirming earlier neuropathological observations), or by a loss of excitatory afferents. While its precise cause remains unknown, the depressed output from the CA3 region was statistically correlated with the learning impairment, and we believe provides a reasonable explanation of this behavioural deficit.

Action Potentials↗

PubMed1988

Postsynaptic control of the induction of long-term changes in efficacy of transmission at neocortical synapses in slices of rat brain.

1. Long-term potentiation (LTP) is an enduring, activity-induced increase in the efficacy of synaptic transmission, which has been considered as a possible neural substrate for learning. Recent experiments have shown that LTP can be induced in hippocampal CA1 neurons when a presynaptic volley is paired repetitively with depolarization of the postsynaptic cell, brought about with intracellularly applied depolarizing current pulses (20, 33). We have repeated these experiments in neocortical neurons, in transverse slices of rat sensorimotor cortex in vitro. 2. Stable intracellular recordings were obtained from 28 neurons (mean resting potential -78 mV, mean spike amplitude 95 mV, mean input resistance 41 M omega) mostly in layers V and VI. Two different afferent pathways were stimulated alternately at 0.2 Hz to evoke subthreshold composite excitatory postsynaptic potentials (EPSPs). One micromolar bicuculline methiodide was added to the bathing medium in most experiments. 3. Repetitive pairing of one afferent volley with a coincident intracellular depolarizing current pulse (100-200 ms long) of a magnitude sufficient to make the neuron fire 6 to 13 action potentials/pulse, gave rise after 30-50 pairings in 4 neurons to a significant enduring increase in the amplitude of the paired EPSP. The increase persisted without decrement for as long as the recording continued (range 15-50 min after the pairing ended) but the amplitude of the unpaired EPSP was unchanged. During the LTP, the membrane potential and the apparent input resistance of the postsynaptic neurons were also unchanged. 4. In two cells a significant prolonged depression of the paired EPSP was induced while the unpaired EPSP was unaffected. Membrane potential and input resistance were not changed. In the remaining 22 cells neither the paired nor the unpaired EPSP was altered. 5. Brief, tetanic stimulation was applied to one afferent pathway in 11 of the neurons in which postsynaptic stimulation had been ineffective. A variety of effects was produced (LTP, depression, or posttetanic potentiation). All the effects of tetanic stimulation were confined to the stimulated pathway. 6. We conclude that LTP can be produced in some neocortical neurons by pairing a presynaptic volley with postsynaptic depolarization, in an experimental paradigm that conforms to Hebb's (17) model of associative conditioning. Depression of the paired EPSP was produced in other cells with the same experimental design.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1981

Enhancement of the 5-HT neurotransmission by antidepressant treatments.

The hypothesis of an etiopathogenic role of 5-HT and that of a mediation by the 5-HT system in the effect of antidepressant treatments have often been confused. Little unequivocal evidence exists for a 5-HT deficit in depression. However, several recent animal and clinical data suggest that the 5-HT system might contribute to the therapeutic effect of various antidepressant treatments. Long-term administration of tricyclic antidepressant (TCA) drugs induces a sensitization of rat forebrain neurons to iontophoretically-applied 5-HT. Repeated electroconvulsive shocks result also in an increased sensitivity of forebrain 5-HT receptors. However, chronic administration of a new antidepressant drug, zimelidine, a potent and long-lasting 5-HT uptake blocker, fails to modify 5-HT receptor sensitivity. These results suggest that enhancement of 5-HT neurotransmission obtained via either pre- or postsynaptic mechanisms might determine the antidepressant effect of these treatments. In a recent clinical study, we observed that lithium administration to TCA-resistant depressive patients induced a rapid relief of depression. It is possible that the presynaptic enhancing effect of lithium on the 5-HT system might unveil the TCA-induced sensitization of the postsynaptic 5-HT receptors. Most depressed patients exhibit marked diurnal variations of mood. Preliminary experiments in rats revealed that the responsiveness of hippocampal neurons to iontophoretically-applied 5-HT is enhanced in the evening. Similar diurnal variations of 5-HT receptor sensitivity might occur in human brain and be related to diurnal variation of mood in depression. Since normal individuals do not show these fluctuations of mood, it is proposed that the "mood regulating system" might become 5-HT dependent in depressed patients.

Animals↗