Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of ethanol (22 mM) on the modulation of synaptic transmission and long-term potentiation (LTP) by the neurosteroid dehydroepiandrosterone sulfate (DHEAS; 10 microM) was examined in the in vitro rat hippocampal slice preparation. The synaptic responses were elicited by Schaffer collateral stimulation and recorded extracellularly in the somatic and dendritic regions of CA1 pyramidal neurons. LTP induction produced an increase (approximately 55% to 75%) in the amplitude of synaptic responses in ethanol and ethanol plus DHEAS (ethanol/DHEAS) treated slices. These increases were significantly smaller than the approximately 130% increase observed previously in slices treated with DHEAS, but were not significantly different from the approximately 82% increase observed in control slices. These results indicate that an ethanol/DHEAS interaction prevents the enhancement of LTP normally observed with DHEAS treatment of hippocampal slices. An ethanol/DHEAS interaction also altered DHEAS's effects on individual synaptic components of the synaptic response to Schaffer collateral stimulation. Ethanol applied before but not after DHEAS prevented DHEAS's enhancement of the NMDA receptor-mediated synaptic component. DHEAS's depression of the GABAA receptor-mediated synaptic component was also blocked by ethanol. Ethanol or DHEAS individually had no effect on the AMPA receptor-mediated synaptic component, but application of ethanol after DHEAS resulted in a small enhancement of this synaptic component, an effect that was not observed if ethanol was applied before DHEAS. These results show that ethanol and DHEAS interact, altering DHEAS's effects on synaptic transmission and LTP in the hippocampus. Such an interaction may be involved in ethanol's actions on the CNS and raises the possibility that ethanol and DHEAS may act via a common site or pathway.
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PMID:Acute alcohol blocks neurosteroid modulation of synaptic transmission and long-term potentiation in the rat hippocampal slice. 892 87

The modulatory action of thyrotropin-releasing hormone (TRH), an endogenously occurring neuropeptide, on synaptic potentials mediated by activation of GABAA or GABAB receptors was studied using intracellular recordings from CA1 pyramidal neurones of the rat hippocampal brain slice preparation. Bath-applied TRH (10 microM) produced a reversible depression of fast IPSPs (mediated by GABAA receptors) induced by electrical stimulation of the stratum lacunosum moleculare (LM) or stratum pyramidale (SP). This phenomenon was not associated with changes in the IPSP reversal potential, resting potential, or input resistance. GABAB receptor-mediated slow IPSPs elicited by SP stimulation were found insensitive to TRH whereas those induced by LM stimulation were attenuated by the peptide. AMPA receptor-mediated EPSPs and postsynaptic responses to isoguvacine or baclofen were unchanged by TRH. These data suggest that the action of TRH on GABAergic transmission was probably exerted at presynaptic level within the local circuitry comprising CA1 neurones. Such an effect of TRH represents an interesting example of transient downregulation of inhibitory processes by a physiological neuropeptide and is expected to augment excitability of pyramidal cells.
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PMID:The neuropeptide thyrotropin-releasing hormone modulates GABAergic synaptic transmission on pyramidal neurones of the rat hippocampal slice. 895 56

The delta 2 glutamate receptors are prominently expressed in Purkinje cells and are thought to play a key role in the induction of cerebellar long-term depression. The synaptic and subsynaptic localization of delta receptors in rat cerebellar cortex was investigated with sensitive and high-resolution immunogold procedures. After postembedding incubation with an antibody raised to a C-terminal peptide of delta 2, high gold particle densities occurred in all parallel fiber synapses with Purkinje cell dendritic spines, whereas other synapses were consistently devoid of labeling. Among the types of immunonegative synapse were climbing fiber synapses with spines and parallel fiber synapses with dendritic stems of interneurons. At the parallel fiber-spine synapse, gold particles signaling delta receptors were restricted to the postsynaptic specialization. By the use of double labeling with two different gold particle sizes, it was shown that delta and AMPA GluR2/3 receptors were colocalized along the entire extent of the postsynaptic specialization without forming separate domains. The distribution of gold particles representing delta receptors was consistent with a cytoplasmic localization of the C terminus and an absence of a significant presynaptic pool of receptor molecules. The present data suggest that the delta 2 receptors are targeted selectively to a subset of Purkinje cell spines and that they are coexpressed with ionotropic receptors in the postsynaptic specialization. This arrangement could allow for a direct interaction between the two classes of receptor.
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PMID:Differential localization of delta glutamate receptors in the rat cerebellum: coexpression with AMPA receptors in parallel fiber-spine synapses and absence from climbing fiber-spine synapses. 898 4

In the lamprey spinal cord, 5-hydroxytryptamine (5-HT) immunoreactivity (ir) is present in the ventromedial plexus originating from intraspinal neurons, ventrolateral column arising from the brainstem, and dorsal column. The latter 5-HT system originates from small dorsal root ganglion neurons. Combined Lucifer yellow intracellular labeling of the intraspinal sensory neurons, dorsal cells, and 5-HT immunohistochemistry showed close appositions between 5-HT-ir fibers and dorsal cell axons. Application of 5-HT depressed monosynaptic EPSPs evoked in giant interneurons by stimulation of single dorsal cells, dorsal roots, or dorsal column without any detectable change in the input resistance of postsynaptic neurons. Furthermore, the amplitude of AMPA-evoked depolarizations in giant interneurons was unaffected by 5-HT. The lack of postsynaptic effects of 5-HT indicates that the decrease of the amplitude of sensory monosynaptic EPSPs by 5-HT is mediated by presynaptic mechanisms. The inhibition of monosynaptic EPSPs by 5-HT was not counteracted by an antagonist of 5-HT1A receptors. 5-HT also reduced the amplitude of the calcium current recorded in isolated dorsal cells and slowed down its kinetics. The inhibition of calcium channels could represent the mechanism mediating the depression of synaptic transmission at the axonal level. These results show that activation of 5-HT receptors on dorsal cell axons as well as on other sensory neurons mediates inhibition of sensory synaptic transmission to giant interneurons. In intact animals, 5-HT could be released from small 5-HT neurons in dorsal root ganglia, which thus may underlie direct sensory-sensory interactions.
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PMID:5-HT inhibits calcium current and synaptic transmission from sensory neurons in lamprey. 903 Jun 37

The brain is able to change the synaptic strength in response to stimuli that leave a memory trace. Long-term potentiation (LTP) and long-term depression (LTD) are forms of activity-dependent synaptic plasticity proposed to underlie memory. The induction of LTP appears mediated by glutamate acting on AMPA and then on NMDA receptors. Cholinergic muscarinic agonists facilitate learning and memory. Acetylcholine depolarizes pyramidal neurons, reduces inhibition, upregulates NMDA channels and activates the phosphoinositide cascade. Postsynaptic Ca2+ rises and stimulates Ca-dependent PK, promoting synaptic changes. Electroencephalographic desynchronization and hippocampal theta rhythm are related to learning and memory, are inducible by cholinergic agonists and elicited by hippocampal cholinergic terminals. Their loss results in memory deficits. Hence, cholinergic pathways may act synergically with glutamatergic transmission, regulating and leading to synaptic plasticity. The stimulation that induces plasticity in vivo has not been established. The patterns for LTP/LTD induction in vitro may be due to the loss of ascending cholinergic inputs. As a rat explores pyramidal cells fire bursts that could be relevant to plasticity.
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PMID:Cholinergic neurotransmission and synaptic plasticity concerning memory processing. 913 Feb 63

One important question concerning the homeostatic regulation of many physiological processes is whether the control mechanisms are purely reflexogenic or whether they may involve neural adaptation in the form of learning and memory in the brainstem. Using a brainstem slice preparation in the rat, we studied the modifiability of neural transmission in the first-order synapses of the medial and commissural nucleus tractus solitarius of the medulla. Sustained low-frequency stimulation (5 Hz) of primary afferent fibers in the tractus solitarius resulted in a phasic depression (accommodation) of synaptic strength as reflected by a concomitant decrease in the evoked excitatory postsynaptic potentials. In one group of neurons (type I), synaptic strength recovered rapidly after low-frequency stimulation, whereas in another group of neurons (type II), synaptic strength remained depressed for >30 min, i.e., manifesting long-term depression (LTD). The latter was switched into a short-term depression lasting 15-25 min after pharmacological blockade of NMDA receptor channels with D-APV or chelation of intracellular calcium ions with EGTA, whereas the accommodation phase was unaffected. Application of an AMPA receptor anti-desensitization agent cyclothiazide abolished the LTD, but not the accommodation response. These results suggest the presence of separate postsynaptic sites for the induction of LTD and accommodation, one being sensitive to cyclothiazide, whereas the other is not. Moreover, the maintenance of LTD is dependent on the level of intracellular Ca2+. These phasic and long-term synaptic plasticity in the nucleus tractus solitarius may play a role in the homeostatic regulation of cardiorespiratory functions.
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PMID:Phasic and long-term depression in brainstem nucleus tractus solitarius neurons: differing roles of AMPA receptor desensitization. 920 19

Ethanol, usually studied in relation to intoxication, is also capable of producing general anesthesia. The most common standard of anesthetic potency is the concentration which produces immobility in response to a noxious stimulus. This concentration will be referred to as the anesthetic concentration. Immobilization is a spinal effect. Ethanol effects were studied in spinal cord from 2-7-day-old rats at concentrations which included the anesthetic concentration in both adult rats (97 mM) and 6-7-day-old rats (235 mM). At neonatal but not adult anesthetic concentrations, ethanol depressed monosynaptic reflex amplitude (mediated by glutamate AMPA receptors + compound action potential). At both neonatal and adult anesthetic concentrations ethanol reversibly depressed the population excitatory postsynaptic potential (pEPSP) (glutamate AMPA and NMDA receptors), the slow ventral root potential (NMDA + metabotropic receptors), and the dorsal root potential (GABA(A) receptors, via glutamate-excited interneurons). Effects were greater on NMDA receptor-mediated components than on AMPA-receptor-mediated components of the pEPSP and greater on NMDA than on metabotropic receptor-mediated components of the slow ventral root potential. The profile of ethanol effects on spinal cord resembles that of inhalation general anesthetics. The results show that both AMPA and NMDA receptor-mediated transmission are sensitive to ethanol and that enhancement of GABAergic neurotransmission is overridden by depression of excitation to the interneurons. They provide no obvious explanation for ethanol's lower general anesthetic potency in the neonate.
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PMID:Ethanol as a general anesthetic: actions in spinal cord. 922 3

A grease-gap preparation for the in vitro rat hippocampal slice has been used to record field excitatory postsynaptic potentials (fEPSPs), extracellular d.c. potential and depolarizations in response to glutamate receptor agonists before, during and after hypoxic/ischaemic episodes in the CA1 region. Synaptic transmission was depressed by hypoxia in a temperature-dependent manner (t1/2 at 28 degrees C, 1.9 +/- 0.2 min; t1/2 at 36 degrees C, 1.0 +/- 0.1 min) but was unaffected by the absence of D-glucose during hypoxia (ischaemia) at 28 degrees C. The reappearance of the fEPSP during hypoxic/ischaemic episodes was a prelude to severe disruptions of synaptic transmission if control conditions were not reinstated within 1 min of the secondary depression of the fEPSP. For a 10 min episode of hypoxia, recovery of synaptic transmission at 28 degrees C (96 +/- 1.5% of control) was significantly better than recovery following either hypoxia at 36 degrees C or ischaemia at 28 degrees C (41 +/- 17.2% and 55 +/- 21% of control, respectively). Chart recordings of the d.c. potential during hypoxia revealed a predominate (67% of all episodes) triphasic sequence of events (i, hyperpolarization; ii, depolarization; iii, post-hypoxic hyperpolarization on reoxygenation). Depolarizing responses to N-methyl-D-aspartate (NMDA, 20-40 microM; in 1 mM extracellular Mg2+), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, 2-10 microM) and L-glutamate (L-Glu, 2-5 mM) could be elicited at times when fEPSPs were completely depressed and up to 20 min into a hypoxic episode, the latest time-point examined. This implies, as others have suggested, that the hypoxic depression of excitatory synaptic transmission is presynaptic in origin. The application of AMPA or NMDA during the hypoxic depression of the fEPSP occasionally resulted in a short-lasting (12-45 min) potentiation (117-143% of control) of the fEPSP on return to normoxia. Furthermore, in other slices, which were exposed to severe metabolic stress, synaptic transmission was depressed to a significantly greater extent than AMPA depolarizations (mean depression; 76 +/- 5% and 28 +/- 8%, respectively).
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PMID:The effects of metabolic stress on glutamate receptor-mediated depolarizations in the in vitro rat hippocampal slice. 925 42

Whole-cell patch clamp recordings of deep dorsal horn neurons were undertaken in 'thick' transverse slices to demonstrate plasticity of primary afferent-evoked synaptic responses following conditioning stimulation. Synaptic plasticity was observed in neurons throughout the age range examined (postnatal days 3-6 and 9-16) but only long-term depression (LTD) was evocable in older animals (P9-16). Both short- and long-latency synaptic responses could undergo long-term potentiation (LTP) and LTD suggesting that AMPA/kainate and NMDA receptor-evoked responses are modifiable.
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PMID:Primary afferent-evoked synaptic plasticity in deep dorsal horn neurons from neonatal rat spinal cord in vitro. 925 64

Synaptic depression of evoked EPSCs was quantified with stimulation frequencies ranging from 0.2 to 100 Hz at the single CNS synapse formed by the calyx of Held in the rat brainstem. Half-maximal depression occurred at approximately 1 Hz, with 10 and 100 Hz stimulation frequencies reducing EPSC amplitudes to approximately 30% and approximately 10% of their initial magnitude, respectively. The time constant of recovery from depression elicited by 10 Hz afferent fiber stimulation was 4.2 sec. AMPA and NMDA receptor-mediated EPSCs depressed in parallel at 1-5 Hz stimulation frequencies, suggesting that depression was induced by presynaptic mechanism(s) that reduced glutamate release. To determine the contribution of autoreceptors to depression, we studied the inhibitory effects of the metabotropic glutamate receptor (mGluR) agonists (1S, 3S)-ACPD and L-AP4 and found them to be reversed in a dose-dependent manner by (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG), a novel and potent competitive antagonist of mGluRs. At 300 microM, CPPG completely reversed the effects of L-AP4 and (1S, 3S)-ACPD, but reduced 5-10 Hz elicited depression by only approximately 6%. CPPG-sensitive mGluRs, presumably activated by glutamate spillover during physiological synaptic transmission, thus contribute on the order of only 10% to short-term synaptic depression. We therefore suggest that the main mechanism contributing to the robust depression elicited by 5-10 Hz afferent fiber stimulation of the calyx of Held synapse is synaptic vesicle pool depletion.
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PMID:Presynaptic depression at a calyx synapse: the small contribution of metabotropic glutamate receptors. 933 89


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