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

The functional organization and synaptic physiology of olfactory bulb glomeruli were studied in rat in vitro slice preparations stained with the voltage-sensitive dye RH-155. Optical signals were recorded with a 100-element photodiode array at high temporal resolution. Pharmacological and ionic manipulations were used to investigate synaptic responses to stimulation of the olfactory nerve layer (ONL). ONL stimulation evoked a sodium-mediated compound action potential that propagated across the ONL and invaded individual glomeruli. This presynaptic volley evoked calcium-dependent synaptic responses the amplitudes of which were largest within the glomerular layer (GL); smaller amplitude responses were recorded in deeper layers of the olfactory bulb. Synaptic responses in the GL were attenuated by the non-NMDA ionotropic glutamate receptor antagonist CNQX; the residual component was suppressed by the NMDA glutamate receptor antagonist AP-5. The GABAA receptor antagonist bicuculline methiodide had little effect, whereas the GABAB receptor agonist baclofen dramatically attenuated ONL-evoked synaptic responses. The effects of baclofen were reversed by the GABAB receptor antagonist CGP35348. Paired-pulse depression of ONL-evoked synaptic responses in the GL was partially reversed by CGP35348. These findings suggest that olfactory nerve axons release glutamate to activate both NMDA and non-NMDA receptors on GL neurons, that GABAA receptor-mediated inhibition has little effect on these responses, and that GABAB receptor-mediated inhibition may act presynaptically on olfactory nerve axons to modulate their inputs to olfactory bulb neurons.
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PMID:Functional organization of rat olfactory bulb glomeruli revealed by optical imaging. 950 19

1. Neuropharmacological actions of all the possible stereoisomers of 3',3'-difluoro-2-(carboxycyclopropyl)glycine (3',3'-difluoro-CCG) were compared with those of the corresponding 2-(carboxycyclopropyl)glycine (CCG) isomers in the isolated spinal cord of newborn rats. (2S,1'S,2'S)- and (2S,1'R,2'S)-2-(2-carboxy-3,3-difluorocyclopropyl)glycine (L-F2CCG-I and L-F2CCG-IV) were the most potent in causing depolarization, their threshold concentrations being approximately 1 microM. 2. The depolarization evoked by L-F2CCG-I (30 microM) was depressed by (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 1 mM (n=4)) to 17+/-3% of the control: this depolarizing action was not decreased by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 100 microM), and only slightly decreased by high concentrations of D-2-amino-5-phosphonopentanoic acid (D-AP5, 100 microM), suggesting that L-F2CCG-I activates mainly metabotropic glutamate receptors. 3. L-F2CCG-I preferentially depressed the monosynaptic component of the spinal reflex approximately 3 times more effectively than (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I). The depressant action of L-F2CCG-I (0.2 microM-0.7 microM) on monosynaptic excitation was antagonized by (2S,1'S,2'S)-2-methyl-2-(carboxycyclopropyl)glycine (MCCG, 0.3 mM-1 mM) and (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4, 0.3 mM). 4. DL-alpha-aminopimelate (10 and 100 microM) selectively potentiated the depression of monosynaptic excitation caused by L-CCG-I (0.2 microM) and L-F2CCG-I (0.1 microM). The actions of (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) (50 nM-0.2 microM), L-2-amino-4-phosphonobutanoic acid (L-AP4) (0.3-1 microM), (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD) (1-7 microM) and baclofen (0.1-0.7 microM) were unaffected by DL-alpha-aminopimelate. The threshold concentration for the potentiating actions of DL-alpha-aminopimelate was 3 microM. 5. The depolarization induced by quisqualate (3 microM, 10 s application) was increased to 115+/-2% and 137+/-5% of the control values during combined application of quisqualate with either 30 microM or 100 microM DL-alpha-aminopimelate, respectively. 6. Following the application and subsequent washout of L-F2CCG-I, DL-alpha-aminopimelate (3-100 microM) decreased the amplitude of the monosynaptic component of spinal reflexes in a concentration-dependent manner, indicating a 'priming' effect of L-F2CCG-I.
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PMID:Potentiation by DL-alpha-aminopimelate of the inhibitory action of a novel mGluR agonist (L-F2CCG-I) on monosynaptic excitation in the rat spinal cord. 951 98

Visually identified and electrophysiologically characterized sympathetic preganglionic neurons (SPNs) were recorded using the whole-cell voltage clamp technique in slices of neonatal rat spinal cord. Monosynaptic excitatory postsynaptic currents (EPSCs) were evoked by electrical stimulation of the nucleus intercalatus in the presence of strychnine (5 microM) and bicuculline (10 microM). These EPSCs were abolished by the antagonist of AMPA-type glutamate receptors, 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX; 10 microM). Bath applied noradrenaline (NA; 0.5-50 microM) dose-dependently and reversibly decreased by up to around 60% the amplitude of the EPSC, without affecting the holding current. The EPSC depression by NA was not accompanied by a change in EPSC reversal potential (around +5 mV), nor were inward currents generated by pressure application of glutamate affected by NA application. A comparable degree of EPSC depression was also seen with the alpha2-adrenoceptor agonist clonidine (5 microM), and the alpha2A-agonist oxymetazoline (5 microM), while the alpha1-agonist phenylephrine (100 microM) caused only a 22% depression. The EPSC depression caused by NA (10 microM) was completely antagonized by either the alpha-antagonist phentolamine (10 microM) or the alpha2-antagonist idazoxan (2 microM). Conversely, the beta-adrenoceptor antagonist popranolol (5 microM), and the alpha1-, alpha2B- and alpha2C-antagonist prazosin (2 microM) were without effect. These results indicate that activation of presynaptic alpha2A-adrenoceptors on inputs to SPNs decreases glutamate release.
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PMID:Presynaptic inhibition by noradrenaline of the EPSC evoked in neonatal rat sympathetic preganglionic neurons. 959 80

1. In embryonic rat hippocampal neurones cultured for < 3 days, kainate induced an inward current at negative potentials that recovered to baseline levels immediately upon termination of agonist application. However, in neurones cultured for longer, the kainate-induced current was often followed by a long-lasting inward current that slowly recovered to baseline levels. The amplitude of the delayed current (Idelay) triggered by kainate was positively related both to the duration of application at constant agonist concentration and to concentration at constant application duration. 2. Idelay could last for several minutes and was accompanied by a conductance increase, which closely paralleled current amplitude. Depression of the kainate-induced current response at receptor level with CNQX or at ionic level with Na+-free solution eliminated Idelay. However, when applied during Idelay neither CNQX nor Na+-free solution had any effect on Idelay. Li+ effected the same response as Na+ in mediating kainate-induced Idelay. 3. GABA-activated Cl- current, which was associated with the same amount of inwardly directed charge flow at the same potential as that induced by kainate, did not trigger a long-lasting delayed current. 4. Idelay depended on the existence of extracellular K+ and its amplitude increased with the increase in K+ concentration. Neither applying Cl-- or Ca2+-free solutions nor increasing intracellular Ca2+ buffering speed and capacity altered Idelay. Exposure to the specific KCa channel blockers apamin and charybdotoxin also failed to alter Idelay. However, Idelay could be blocked by Cs+, Ba2+ and high concentrations of 4-aminopyridine (4-AP) and TEA. 5. Inside-out excised patch-clamp recordings revealed that low density or highly clustered Na+-activated K+ channels were expressed in the cell bodies of cultured embryonic rat hippocampal neurones. These could be the elementary channels underlying Idelay.
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PMID:Kainate induces an intracellular Na+-activated current in cultured embryonic rat hippocampal neurones. 966 Aug 88

1. Electrical stimulation (10 s) of the ethmoidal nerve (EN5) evokes the nasotrigeminal reflex responses, including apnoea, bradycardia and rise in arterial blood pressure. In the present study, we examined the involvement of N-methyl-D-aspartate (NMDA), AMPA/kainate, (gamma-aminobutyric acidA (GABAA) and glycine receptors in the Kolliker-Fuse (KF) nucleus in the mediation of the nasotrigeminal reflex responses. 2. Unilateral injections (n = 6) of 50-100 nl of the NMDA receptor antagonist AP5 into the KF area led to a significant blockade of the EN5-evoked respiratory depression and bradycardia. Injections placed into the midlevel of the KF area were most effective (80-90 % blockade). The rise in arterial blood pressure remained unaffected. 3. Unilateral injections (n = 6) of the AMPA/kainate receptor antagonist CNQX into the KF area failed to block EN5-evoked autonomic responses significantly. 4. Unilateral injections (n = 5) of the GABAA receptor antagonist bicuculline enhanced the EN5-evoked respiratory depression and bradycardia. The effect persisted for up to 30 s after stimulation. Bicuculline injections into the midlevel of the KF area were most effective. The increase in arterial blood pressure remained unaffected. 5. Unilateral injections (n = 5) of the glycine receptor antagonist strychnine into the KF area did not produce any significant effects on EN5-evoked autonomic responses. 6. Our results suggest that the KF area represents a mandatory relay for the nasotrigeminally induced apnoea and bradycardia which are predominantly mediated by NMDA receptors in the KF. Furthermore, it appears that KF neurons are under a potent GABAergic inhibitory control. The EN5-evoked rise in arterial blood pressure was not altered by any of the drugs and, therefore, appears not to be mediated via the KF.
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PMID:NMDA and GABAA receptors in the rat Kolliker-Fuse area control cardiorespiratory responses evoked by trigeminal ethmoidal nerve stimulation. 966 Aug 94

1. EPSCs were recorded under whole-cell voltage clamp at room temperature from Purkinje cells in slices of cerebellum from 12- to 14-day-old rats. EPSCs from individual climbing fibre (CF) inputs were identified on the basis of their large size, paired-pulse depression and all-or-none appearance in response to a graded stimulus. 2. Synaptic transmission was investigated over a wide range of experimentally imposed release probabilities by analysing fluctuations in the peak of the EPSC. Release probability was manipulated by altering the extracellular [Ca2+] and [Mg2+]. Quantal parameters were estimated from plots of coefficient of variation (CV) or variance against mean conductance by fitting a multinomial model that incorporated both spatial variation in quantal size and non-uniform release probability. This 'multiple-probability fluctuation' (MPF) analysis gave an estimate of 510 +/- 50 for the number of functional release sites (N) and a quantal size (q) of 0.5 +/- 0.03 nS (n = 6). 3. Control experiments, and simulations examining the effects of non-uniform release probability, indicate that MPF analysis provides a reliable estimate of quantal parameters. Direct measurement of quantal amplitudes in the presence of 5 mM Sr2+, which gave asynchronous release, yielded distributions with a mean quantal size of 0.55 +/- 0.01 nS and a CV of 0.37 +/- 0.01 (n = 4). Similar estimates of q were obtained in 2 mM Ca2+ when release probability was lowered with the calcium channel blocker Cd2+. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 1 microM) reduced both the evoked current and the quantal size (estimated with MPF analysis) to a similar degree, but did not affect the estimate of N. 4. We used MPF analysis to identify those quantal parameters that change during frequency-dependent depression at climbing fibre-Purkinje cell synaptic connections. At low stimulation frequencies, the mean release probability (pr) was unusually high (0.90 +/- 0.03 at 0.033 Hz, n = 5), but as the frequency of stimulation was increased, pr fell dramatically (0.02 +/- 0.01 at 10 Hz, n = 4) with no apparent change in either q or N. This indicates that the observed 50-fold depression in EPSC amplitude is presynaptic in origin. 5. Presynaptic frequency-dependent depression was investigated with double-pulse and multiple-pulse protocols. EPSC recovery, following simultaneous release at practically all sites, was slow, being well fitted by the sum of two exponential functions (time constants of 0.35 +/- 0.09 and 3.2 +/- 0.4 s, n = 5). EPSC recovery following sustained stimulation was even slower. We propose that presynaptic depression at CF synapses reflects a slow recovery of release probability following release of each quantum of transmitter. 6. The large number of functional release sites, relatively large quantal size, and unusual dynamics of transmitter release at the CF synapse appear specialized to ensure highly reliable olivocerebellar transmission at low frequencies but to limit transmission at higher frequencies.
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PMID:Locus of frequency-dependent depression identified with multiple-probability fluctuation analysis at rat climbing fibre-Purkinje cell synapses. 966 Sep

General anesthetics are thought to depress the central nervous system (CNS) by acting at synapses; however, only a few studies have compared effects on axonal conduction with effects on synaptic responses using mammalian CNS preparations. The present study used glutamate receptor antagonists (CNQX/APV) or low calcium to block synaptic transmission, allowing Schaffer-collateral axon fiber volleys to be recorded from rat hippocampal brain slices. Since fiber volleys are compound action potentials, they provide a measure of axonal conduction in Schaffer-collateral fibers. Clinical concentrations of the inhalational anesthetic, halothane (1 rat MAC, 1.2 vol.%), produced an 18 +/- 2.3% depression of fiber volley amplitudes (mean +/- S.D.; p < 0.001 ANOVA, n = 10). Depression of action potential conduction accounted for approximately 30% of the overall depression of synaptic transmission produced by halothane at this concentration. Halothane-induced fiber volley depression occurred with little change in conduction velocity, similar to the effect seen with decreased stimulus intensity, but significantly different from the decreased velocity produced by tetrodotoxin (100 nM, p < 0.005). The results indicate that halothane can depress axonal conduction at clinically relevant concentrations and that this depression could contribute to the CNS depression that is associated with anesthesia.
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PMID:Halothane depresses action potential conduction in hippocampal axons. 968 73

In young rats, low frequency (1-2 Hz) stimulation of the Schaffer collaterals for 15 min induces in the CA1 area of the hippocampus a homosynaptic and N-methyl-D-aspartate receptor-dependent form of long-term depression (LTD) of synaptic efficacy. In the adults, while a similar stimulation paradigm is able to depress previously potentiated synapses, it leads to conflicting results when applied to naive synapses. In the present experiments, different stimulation paradigms have been used to induce LTD in the CA1 area of the adult rat hippocampus in vitro. Thus, stimulation of the afferent pathway at frequencies higher than those used to produce LTD in young animals (5-10 Hz, for 15 min) reliably induced a homosynaptic form of LTD. This form of LTD was associated with a significant increase in paired-pulse facilitation ratio and was insensitive to ionotropic (CNQX, 10 microM and CPP, 20 microM) and metabotropic (S-MCPG, 1 mM) glutamate receptors antagonists, suggesting a presynaptic mechanism for both LTD induction and expression. In conclusion, our experiments clearly show that LTD is not a purely developmental phenomenon but is present also in mature rats, which possess the whole machinery for LTD induction and this will greatly enhance the flexibility and the storing capacity of neuronal circuits.
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PMID:A novel form of long-term depression in the CA1 area of the adult rat hippocampus independent of glutamate receptors activation. 975 65

Acetylcholine (ACh) exerts a crucial role in learning and memory. The striatum contains the highest concentration of this transmitter in the brain. This structure expresses two different forms of synaptic plasticity, long-term depression (LTD) and long-term potentiation (LTP), which might contribute to the storage of motor skills and some cognitive processes. We have investigated the role of M2-like muscarinic receptors in striatal LTP by utilizing intracellular recordings in vitro from a rat corticostriatal slice preparation. Methoctramine (250 nM), an antagonist of M2-like muscarinic receptors, enhanced striatal LTP induced in the absence of external magnesium (Mg2+) by high-frequency stimulation (HFS) of corticostriatal fibres. Methoctramine did not affect the amplitude of excitatory postsynaptic potentials (EPSPs) when bath applied either before or after the conditioning tetanus suggesting that a critical increase of ACh concentrations is produced only during HFS. Methoctramine per se failed to enhance the NMDA-mediated EPSPs recorded in the absence of external Mg2+ and in the presence of 10 microM CNQX. Methoctramine antagonized the presynaptic inhibitory action of neostigmine, an inhibitor of ACh-esterase, and oxotremorine, an agonist of M2-like muscarinic receptors. These data indicate that the activation of M2-like muscarinic receptors exerts a negative influence on striatal LTP, probably by reducing the release of glutamate from corticostriatal fibres and they suggest a complex modulatory effect of ACh in striatal synaptic plasticity.
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PMID:Blockade of M2-like muscarinic receptors enhances long-term potentiation at corticostriatal synapses. 975 72

It has been suggested that the induction of long-term depression (LTD) may be developmentally regulated since LTD can be readily induced by LFS in slices from young but not adult animals. However, we have recently reported that paired pulse low frequency stimulation (PP-LFS) can reliably induce LTD in the CA1 region of adult hippocampal slices. We now describe the role of glutamate receptors in the induction of LTD in adult hippocampus. The induction of LTD was prevented by the combined application of AMPA/kainate and metabotropic glutamate (mGlu) receptor antagonists (CNQX and LY341495). However, LTD was not blocked by the co-application of NMDA and mGlu receptor antagonists nor by the co-application of NMDA and AMPA/kainate receptor antagonists. Taken together, the above results suggest that activation of either AMPA/kainate or mGlu receptors is sufficient to induce LTD. Therefore, these results suggest that PP-LFS can efficiently activate AMPA/kainate and mGlu receptors in order to induce long-lasting synaptic depression in the CA1 region of the adult hippocampus in vitro.
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PMID:Induction of LTD in the adult hippocampus by the synaptic activation of AMPA/kainate and metabotropic glutamate receptors. 1022 53


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