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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of tetanic activation of corticostriatal glutamatergic fibers was studied in striatal slices by utilizing extracellular and intracellular recording techniques. Tetanic stimulation produced a long-term synaptic depression (LTD) (> 2 h) of both extracellularly recorded field potentials and intracellularly recorded EPSPs. LTD was not coupled with changes of intrinsic membrane properties of the recorded neurons. In some neurons, repetitive cortical activation produced a short-term posttetanic potentiation (1-3 min). Subthreshold tetanic stimulation, which under control condition did not cause LTD, induced LTD when associated with membrane depolarization. Moreover, LTD was not expressed in cells in which the conditioning tetanus was coupled with hyperpolarization of the membrane. Bath application of aminophosphonovalerate (30-50 microM), an antagonist of NMDA receptors, did not affect the amplitude of the synaptic potentials and the expression of LTD. Striatal LTD was significantly reduced by the pretreatment of the slices with 30 microM 2-amino-3-phosphonopropionic acid, an antagonist of glutamate metabotropic receptors. LTD was not blocked by bicuculline (30 microM), a GABA(A) receptor antagonist. Scopolamine (3 microM), an antagonist of muscarinic receptors, induced a slight, but significant, increase of the amplitude of LTD. Both SCH 23390 (3 microM), an antagonist of D1 dopamine (DA) receptors, and I-sulpiride (1 microM), an antagonist of D2 DA receptors, blocked LTD. LTD was also absent in slices obtained from rats in which the nigrostriatal DA system was lesioned by unilateral nigral injection of 6-hydroxydopamine. In DA-depleted slices, LTD could be restored by applying exogenous DA (30 microM) before the conditioning tetanus. In DA-depleted slices, LTD could also be restored by coadministration of SKF 38393 (3-10 microM), a D1 receptor agonist, and of LY 171555 (1-3 microM), a D2 receptor agonist. Application of a single class of DA receptor agonists failed to restore LTD. These data show that striatal LTD requires three main physiological and pharmacological conditions: (1) membrane depolarization and action potential discharge of the postsynaptic cell during the conditioning tetanus, (2) activation of glutamate metabotropic receptors, and (3) coactivation of D1 and D2 DA receptors. Striatal LTD may alter the output signals from the striatum to the other structures of the basal ganglia. This form of synaptic plasticity can influence the striatal control of motor activity.
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PMID:Long-term synaptic depression in the striatum: physiological and pharmacological characterization. 135 31

The ability of serotonin to modulate GABA-mediated synaptic input to substantia nigra pars reticulata (SNr) neurons was investigated with the use of whole-cell patch-clamp recording from slices of rat midbrain. Fast evoked GABA(A) receptor-mediated synaptic currents (IPSCs) were attenuated reversibly approximately 60% by serotonin, which also caused an inward current with reversal potential of -25 mV. This inward current was blocked by the 5-HT2 receptor antagonist ritanserin, whereas the IPSC depression was blocked by the 5-HT1B receptor antagonist pindolol. The amplitude ratio of IPSC pairs (50 msec interpulse interval) was enhanced by serotonin (in ritanserin) and also by the GABA(B) receptor agonist baclofen (which also depressed the IPSC), consistent with a presynaptic site of action in both cases. In contrast, spontaneous tetrodotoxin-sensitive GABA(A) synaptic currents (sIPSCs) were increased in frequency by serotonin (an action that was sensitive to ritanserin, but not pindolol) but reduced in frequency by baclofen. SNr neurons therefore receive inhibitory synaptic input mediated by GABA(A) receptors from at least two distinct sources. One, probably originating from the striatum, may be depressed via presynaptic 5-HT1B and GABA(B) receptors. The second is likely to arise from axon collaterals of SNr neurons themselves and is facilitated by an increase in firing via postsynaptic, somatodendritic 5-HT2C receptor activation, but it is depressed by GABA(B) receptor activation. Thus, serotonin can both depolarize and disinhibit SNr neurons via 5-HT2C and 5-HT1B receptors, respectively, but excitation may be limited by GABA released from axon collaterals.
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PMID:Differential actions of serotonin, mediated by 5-HT1B and 5-HT2C receptors, on GABA-mediated synaptic input to rat substantia nigra pars reticulata neurons in vitro. 892 13

The possibility for long-term depression (LTD) of synaptic transmission in layer II/III horizontal connections within motor cortex was investigated using field potentials and intracellular recordings in rat brain slices. The LTD was induced by low-frequency stimulation at 2 Hz for 10 min in sites displaced horizontally by 0.5 mm from the stimulating electrode. Response amplitude measured 25-30 min after 2 Hz stimulation ended was 79% of baseline values (n = 13) at half maximal stimulation and 59% when 2 Hz stimulus intensity was doubled (n = 10). In 13/15 tested cases LTD in horizontal connections was specific to the activated pathway. Intracellular recordings from six neurons confirmed synaptic character of response depression. Horizontal connections in which LTD was induced retained the capability of increasing synaptic strength. Long-term potentiation could be induced in previously depressed pathways by simultaneous theta burst stimulation of two converging horizontal inputs combined with transient local application of GABA(A) receptor antagonist bicuculline methiodide (mean increase: 45 +/- 8% n = 6) or by simultaneous theta burst stimulation of converging horizontal and vertical inputs (mean change: 26 +/- 6%, n = 5). These data demonstrate that activity-dependent mechanisms may regulate bidirectionally the effectiveness of horizontal synaptic coupling between cortical neurons, thus forming a potential mechanism for plasticity of cortical connections and the representation patterns they support.
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PMID:Long-term depression of horizontal connections in rat motor cortex. 908 17

Dendritic arborization permits convergence of synaptic inputs and their integration in single neurons. The granule neuron in the dentate gyrus represents a relatively simple example where anatomically and functionally distinct medial and lateral perforant pathways terminate on different regions of the dendritic tree. High-frequency stimulation of either pathway alone results in the induction of long-term potentiation. However, whether the potentiated synapses in different parts of the dendrites interact is not known. In this study we have compared long-term potentiation and synaptic interactions in the lateral and medial perforant pathways in the "disinhibited" hippocampal slice preparation in the presence of the GABA(A) receptor blocker bicuculline. The data show that the magnitude of long-term potentiation induced by tetanic stimulation was similar in both pathways, but differences between the two pathways were revealed after two or more tetanizations. A significantly smaller capacity for further long-term potentiation in the lateral, as compared to the medial, perforant pathway was found and can be attributed to stronger postsynaptic GABA(B) inhibition in distal dendrites of granule neurons. Blockade of GABA(B) inhibition with CGP36742 (100 microM) unmasked additional long-term potentiation in the lateral pathway. Presynaptically, GABA(B) receptors produced a short-lasting heterosynaptic depression in the medial pathway, which was reduced by CGP36742. Coincident activation of the two pathways boosted long-term potentiation only in the medial pathway. We propose that the interactions between the two pathways are orchestrated to maximize associative long-term potentiation in the medial pathway; this may be important for types of learning attributed to the hippocampus.
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PMID:Effect of GABA(B) receptors on synaptic interactions in dentate gyrus granule neurons of the rat. 917 69

Effects of enkephalin and selective opioid-receptor agonists on GABA-induced current were examined in dissociated neurons of bullfrog dorsal root ganglia (DRG) by using whole-cell patch-clamp method. Leucine- (Leu)-enkephalin and methionine- (Met)-enkephalin depressed GABA(A) receptor-mediated currents. DPDPE, DAMGO and dynorphin-A (Dyn-A) also depressed the inward current produced by GABA; the order of agonist potency was DPDPE > DAMGO > Dyn-A. Naloxone blocked the inhibitory effects of enkephalins and other opioid agonists on the GABA current. Naltrindole (NTI), a delta-receptor antagonist, prevented the DPDPE-induced depression of the GABA current. beta-Funaltrexamine (beta-FNA), a mu-receptor antagonist, reduced the DAMGO-induced depression of GABA currents. Nor-binaltorphimine (nor-BNI), a kappa-receptor antagonist, reduced the effects of Dyn-A in depressing the GABA current. The results suggest that enkephalin down-regulates GABA(A) receptor function through mainly delta- and mu-opioid receptors in bullfrog DRG neurons.
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PMID:Opioid peptides modulate GABA(A) receptor responses in neurons of bullfrog dorsal root ganglia. 920 45

Paired-pulse depression (PPD) and facilitation are found at many synapses in the central nervous system. In the present study, we aimed to characterise the paired-pulse behaviour of evoked postsynaptic potentials in the superficial layers of slices of the superior colliculus (SC) of adult guinea-pigs. We observed PPD for inter-stimulus intervals between 10 and 500 ms, for both high (90% of maximum) and low (30% of maximum) stimulus intensities. This depression could be converted into a facilitation when the probability of transmitter release was reduced in low Ca2+/high Mg2+ solution, but only when the low stimulus intensity was applied. Elimination of GABA(A) receptor mediated currents by bicuculline caused an enhanced general excitation and enhanced PPD. Application of the GABA(B) receptor antagonist CGP35348 reduced PPD, suggesting the contribution of slow inhibitory postsynaptic currents. The NMDA receptor antagonist D,L-amino-5-phosphonovaleric acid (APV) did not lead to major alterations of PPD. We conclude that presynaptic mechanisms affecting Ca2+-dependent glutamate release are crucial for PPD in the superficial SC. Nevertheless, postsynaptic inhibitory components and probably polysynaptic pathways also seem to contribute to PP behaviour in the SC. Moreover, PPD in the SC has a different profile compared with other brain areas. Here, PPD may be crucially involved in setting the threshold for novel vs. background stimulation, since the SC is known to trigger orienting responses towards novel sensory stimuli.
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PMID:Paired-pulse depression in the superficial layers of the guinea-pig superior colliculus. 944 21

The group I specific metabotropic glutamate (mGlu) receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) (100 microM, 10 min) induced long-term depression (LTD) of synaptic transmission in the CA1 region of adult rat hippocampal slices, measured using a grease-gap recording technique. In "normal" (1 mM Mg2+-containing) medium, LTD (measured 30 min after washout of DHPG) was small (13+/-3%), but LTD was enhanced if DHPG was applied when the tissue was made hyperexcitable, either by omitting Mg2+ from the perfusate (35+/-3%) or by adding the GABA(A) receptor antagonist picrotoxin (29+/-2%). The N-methyl-D-aspartate (NMDA) receptor antagonist AP5 (100 microM) substantially reduced the generation of DHPG-induced LTD in Mg2+-free medium, but had little effect on LTD induced in the presence of picrotoxin. In Mg2+-free medium, the threshold concentration of DHPG required to induce LTD was between 1 and 3 microM. Neither agonists specific for group II (100 nM DCG-IV or 1 microM LY354740) or group III (10 microM L-AP4) mGlu receptors or a combined group I and II agonist (30-100 microM (1S,3R)-ACPD) induced LTD. However, an agonist (1 mM CHPG) which activates mGlu5 but not mGlu1 receptors did induce LTD. Surprisingly, DHPG-induced LTD was reversed by mGlu receptor antagonists, applied hours after washout of DHPG. DHPG-induced LTD did not occlude with LTD induced by synaptic activation (1200 stimuli delivered at 2 Hz), in Mg2+-free medium. These data show that activation of group I mGlu receptors (probably mGlu5) can induce LTD and that this mGlu receptor-mediated LTD may, or may not, require activation of NMDA receptors, depending on the experimental conditions.
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PMID:The group I mGlu receptor agonist DHPG induces a novel form of LTD in the CA1 region of the hippocampus. 951 22

The modulatory effects of endogenous serotonin on the synaptic transmission and epileptiform activity were studied in the rat hippocampus with the use of extracellular and intracellular recording techniques. Field excitatory postsynaptic potential was reversibly depressed by serotonin in a concentration-dependent manner. Intracellular recordings revealed that serotonin-mediated synaptic depression was unaffected by extracellular Ba2+ or intracellular application of Cs+ while the postsynaptic hyperpolarizing effect was completely blocked. Epileptiform activity induced by picrotoxin (50 microM), a GABA(A) receptor antagonist, was also dose-dependently suppressed by serotonin. The antiepileptic effect was mimicked by 5-hydroxytryptamine1A agonist and was blocked by 5-hydroxytryptamine1A antagonists. 5-Hydroxytryptamine2 antagonist had no effect on the modulation. Similarly, fluoxetine, a selective serotonin re-uptake blocker, potently inhibited the epileptiform activity and this effect was blocked by 5-hydroxytryptamine1A receptor antagonist. Depletion of endogenous serotonin by pretreating the slices with p-chloroamphetamine completely prevented the antiepileptic action of fluoxetine, without modifying the action of serotonin in the same cells. These results suggest that the antiepileptic action of fluoxetine is due to an enhancement of endogenous serotonin which in turn is mediated by 5-hydroxytryptamine1A receptor. Endogenous serotonin transmission in the hippocampus is therefore capable of limiting the development and propagation of seizure activity.
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PMID:Endogenous serotonin inhibits epileptiform activity in rat hippocampal CA1 neurons via 5-hydroxytryptamine1A receptor activation. 969 13

A large body of evidence has accumulated in recent years pointing towards the GABA(A) receptor as a primary determinant of volatile anesthetic action (Franks and Lieb, 1994). Nevertheless, our understanding of the function of the central nervous system (CNS) remains sufficiently incomplete that other mechanisms of CNS depression remain to be examined. We have studied a new family of potassium (K+) channels which function as regulators of the baseline excitability of neuronal tissue. As such they must be considered potential targets for volatile anesthetic action and as a possible mechanism by which volatile anesthetics act to allow patients to undergo noxious surgical stimulation.
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PMID:Baseline K+ channels as targets of general anesthetics: studies of the action of volatile anesthetics on TOK1. 1004 56

Modulation of GABA function following 1 week oral administration of flurazepam (FZP) was investigated in chloride-loaded, rat hippocampal CA1 pyramidal neurons. Rats were sacrificed 2 or 7 days after ending drug treatment, when anticonvulsant tolerance was present or absent in vivo, respectively. Spontaneous (s)IPSCs and miniature (m)IPSCs were recorded using whole-cell voltage-clamp techniques. s/mIPSCs were bicuculline-sensitive, voltage-dependent, and reversed their polarity at 0 mV, the predicted E(Cl-). Comparisons of s/mIPSCs between FZP-treated and control groups were made at Vh = -90, -70, and -50 mV. The frequency of sIPSCs, but not mIPSCs, was significantly decreased in FZP-treated neurons 2 days, but not 7 days, after FZP treatment, suggesting a decrease in interneuron activity. These conclusions were supported by the negative findings of additional studies of [3H]GABA release from hippocampal slices and [3H]GABA uptake from hippocampal synaptosomes. The lack of change in the paired-pulse depression of GABA(B)-mediated IPSPs suggested that autoreceptor function was also not impaired following chronic FZP treatment. A large reduction in both sIPSC and mIPSC amplitude (60%) in FZP-treated neurons, the absence of mIPSCs in one-third of FZP-treated cells, and a measurable reduction in synaptic and unitary conductance confirmed that postsynaptic GABA(A) receptor function was profoundly impaired in FZP-treated CA1 neurons. Zolpidem, an alpha1-selective benzodiazepine receptor ligand, enhanced mIPSC amplitude and decay, but its ability to prolong mIPSC decay was reduced in FZP-treated neurons. Several pre- and postsynaptic changes at GABAergic synapses on CA1 pyramidal cells might be related to the decreased tonic GABA inhibition in FZP-treated CA1 neurons associated with the expression of benzodiazepine anticonvulsant tolerance.
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PMID:Benzodiazepine tolerance at GABAergic synapses on hippocampal CA1 pyramidal cells. 1005 Nov 7


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