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)

Synaptic circuitry in the rat lateral amygdala (AL) was studied in brain slices using electrophysiological recordings. Electrical stimulation of external and internal capsules evoked an EPSC followed by a sequence of GABA(A) and GABA(B) receptor-mediated IPSC in principal neurons. Paired stimulation of either afferents resulted in a significant reduction ( approximately 45%) of the second GABA(A) receptor-mediated IPSC. A priming stimulation, consisting of a priming pulse to one pathway followed by a pulse to the other pathway, resulted in a strong depression of the second IPSC basically identical to that during paired stimulation. Paired- and primed-pulse depressions were largely relieved by 10 micrometer CGP 55845A, indicating regulation through presynaptic GABA(B) receptors. Furthermore, putative interneurons responded with EPSCs of constant latencies to minimal stimulation of both cortical and thalamic fibers, indicating convergent monosynaptic input. At higher stimulation strength, an approximately 15% reduction of EPSCs occurred in interneurons after paired and primed stimulation, which was not sensitive to CGP 55845A. These findings indicate that a rather homogeneous population of interneurons exists in the AL with respect to their afferent connectivity, in that they receive convergent input through putative thalamic and cortical fibers, both directly and indirectly (through principal neurons), and mediate inhibitory control of postsynaptic principal neurons. This symmetrically built GABAergic circuitry can be of functional significance, given the distinctive role of the two afferent input systems for the mediation of different components of fear responses and the importance of GABAergic mechanisms for limitation of excessive neuronal activity.
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PMID:Putative cortical and thalamic inputs elicit convergent excitation in a population of GABAergic interneurons of the lateral amygdala. 1110 1

1. Unitary inhibitory postsynaptic currents (uIPSCs) were characterised between 23 synaptically coupled interneurones at the border of stratum radiatum and lacunosum-moleculare (LM) and CA1 pyramidal cells (PYR) using dual whole-cell recordings and morphological identification in rat hippocampal slices. 2. LM interneurones presented a morphology typical of stellate cells, with a fusiform soma as well as dendritic and axonal arborisations in stratum radiatum and lacunosum-moleculare. 3. Single spikes in interneurones triggered uIPSCs in pyramidal cells that were blocked by the GABA(A) antagonist bicuculline and mediated by a chloride conductance. The latency, rise time, duration and decay time constant of uIPSCs were a function of amplitude in all pairs, suggesting a homogeneity in the population sampled. 4. During paired pulse stimulation, individual LM-PYR connections exhibited facilitation or depression. The paired pulse ratio was inversely related to the amplitude of the first response. The transition from facilitation to depression occurred at 26 % of the maximal amplitude of the first uIPSC. Paired pulse depression was not modified by CGP 55845 and thus was GABA(B) receptor independent. 5. CGP 55845 failed to modify the amplitude of uIPSCs, suggesting an absence of tonic presynaptic GABA(B) inhibition at LM-PYR connections. 6. Increasing GABA release by repetitive activation of interneurones failed to induce GABA(B) IPSCs. With extracellular minimal stimulation, increasing stimulation intensity above threshold, or repetitive activation, evoked GABA(B) IPSCs, probably as a result of coactivation of several GABAergic fibres. 7. Thus, dendritic inhibition by LM interneurones involves GABA(A) uIPSCs with kinetics dependent on response amplitude and subject to GABA(B)-independent paired pulse plasticity.
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PMID:Unitary synaptic currents between lacunosum-moleculare interneurones and pyramidal cells in rat hippocampus. 1130 57

Unitary IPSCs elicited by fast-spiking (FS) interneurons in layer V pyramidal cells of the neocortex were studied by means of dual whole-cell recordings in acute slices. FS to pyramidal cell unitary IPSCs were depressed by (RS)-S-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) (ATPA), a kainate (KA) receptor agonist, and by the endogenous agonist l-glutamate in the presence of AMPA, NMDA, mGluR, and GABA(B) receptor antagonists. This effect was accompanied by an increase in failure rate of synaptic transmission, in the coefficient of variation, and in the paired pulse ratio, indicating a presynaptic origin of the IPSC depression. Pairing the activation of the presynaptic neuron with a depolarization of the postsynaptic cell mimicked the decrease of unitary IPSCs, and this effect persisted when postsynaptic sodium action potentials were blocked with the local anesthetic QX314. The effects of ATPA, glutamate, and of the pairing protocol were almost totally blocked by CNQX. These data suggest that KA receptors located on presynaptic FS cell terminals decrease the release of GABA and can be activated by glutamate released from the somatodendritic compartment of the postsynaptic pyramidal cells.
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PMID:Kainate receptors regulate unitary IPSCs elicited in pyramidal cells by fast-spiking interneurons in the neocortex. 1131 83

In many areas of the nervous system, excitatory and inhibitory synapses are reconfigured during early development. We have previously described the anatomical refinement of an inhibitory projection from the medial nucleus of the trapezoid body to the lateral superior olive in the developing gerbil auditory brain stem. Furthermore, these inhibitory synapses display an age-dependent form of long-lasting depression when activated at a low rate, suggesting that this process could support inhibitory synaptic refinement. Since the inhibitory synapses release both glycine and GABA during maturation, we tested whether GABA(B) receptor signaling could initiate the decrease in synaptic strength. When whole cell recordings were made from lateral superior olive neurons in a brain slice preparation, the long-lasting depression of medial nucleus of the trapezoid body-evoked inhibitory potentials was eliminated by the GABA(B) receptor antagonist, SCH-50911. In addition, inhibitory potentials could be depressed by repeated exposure to the GABA(B) receptor agonist, baclofen. Since GABA(B) receptor signaling may not account entirely for inhibitory synaptic depression, we examined the influence of neurotrophin signaling pathways located in the developing superior olive. Bath application of brain-derived neurotrophic factor or neurotrophin-3 depressed evoked inhibitory potentials, and use-dependent depression was blocked by the tyrosine kinase antagonist, K-252a. We suggest that early expression of GABAergic and neurotrophin signaling mediates inhibitory synaptic plasticity, and this mechanism may support the anatomical refinement of inhibitory connections.
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PMID:GABA(B) and Trk receptor signaling mediates long-lasting inhibitory synaptic depression. 1143 32

gamma-Aminobutyric acid (GABA) is a principal inhibitory neurotransmitter in vertebrate nervous system. The metabotropic receptor for GABA, GABA(B) receptor, is characterized as a G protein-coupled receptor subtype. In the present study, GABA(B) receptor-like immunoreactivity (GABA(B)R-LI) in the rat spinal cord and dorsal root ganglion (DRG), as well as GABA(B) receptor-mediated depression in the spinal dorsal horn were examined by using immunohistochemistry and whole-cell voltage-clamp recording technique, respectively. Under light microscope, GABA(B)R-LI was densely found in laminae I and II of the dorsal horn. DRG cells of various diameters also showed GABA(B)R-LI. Electron microscopy further revealed that GABA(B)R-LI was also localized in terminals of myelinated, unmyelinated fibers as well as the somatodendritic sites of dorsal horn neurons. Bath application of a GABA(B) receptor agonist, baclofen (10 microM, 30 s), induced a slow outward (inhibitory) current in dorsal horn neurons. This slow current was depressed when the postsynaptic G protein-coupled receptor was inhibited, indicating the postsynaptic action of baclofen. Under the condition of postsynaptic GABA(B) receptor being inhibited, baclofen (10 microM, 60 s) depressed large (Abeta) and fine (C, Adelta) afferent fiber-evoked monosynaptic excitatory postsynaptic currents, indicating presynaptic inhibition of GABA(B) receptor on elicited neurotransmitter release. Taken together, the results suggest that baclofen-sensitive GABA(B) receptor is expressed pre- and postsynaptically on primary afferent fibers and neurons in the spinal dorsal horn; activation of GABA(B) receptor in the dorsal horn postsynaptically hyperpolarizes dorsal horn neurons and presynaptically inhibits primary afferents.
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PMID:Distribution and depression of the GABA(B) receptor in the spinal dorsal horn of adult rat. 1154 48

In 1991 a new type of G-protein-coupled receptor (GPCR) was cloned, the type 1a metabotropic glutamate (mGlu) receptor, which, despite possessing the defining seven-transmembrane topology of the GPCR superfamily, bore little resemblance to the growing number of other cloned GPCRs. Subsequent studies have shown that there are eight mammalian mGlu receptors that, together with the calcium-sensing receptor, the GABA(B) receptor (where GABA is gamma-aminobutyric acid) and a subset of pheromone, olfactory and taste receptors, make up GPCR family C. Currently available data suggest that family C GPCRs share a number of structural, biochemical and regulatory characteristics, which differ markedly from those of the other GPCR families, most notably the rhodopsin/family A GPCRs that have been most widely studied to date. This review will focus on the group I mGlu receptors (mGlu1 and mGlu5). This subgroup of receptors is widely and differentially expressed in neuronal and glial cells within the brain, and receptor activation has been implicated in the control of an array of key signalling events, including roles in the adaptative changes needed for long-term depression or potentiation of neuronal synaptic connectivity. In addition to playing critical physiological roles within the brain, the mGlu receptors are also currently the focus of considerable attention because of their potential as drug targets for the treatment of a variety of neurological and psychiatric disorders.
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PMID:Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: prototypic family C G-protein-coupled receptors. 1167 21

Long-term potentiation of the hippocampal-septal pathway was examined by intracellular recording techniques. High frequency stimulation (two 100-Hz 1-s trains with a 20-s interval between them) of the hippocampal CA3 area resulted in a transient depolarization in rat lateral septal nucleus neurons. High frequency stimulation was followed by a facilitation of fast and slow inhibitory postsynaptic potentials, lasting for more than 2 h, but not by a long-lasting increase in the excitatory postsynaptic potential in the normal solution. Long-term potentiation (>2 h) of the excitatory postsynaptic potential did not appear in 74% of neurons tested, even when the fast inhibitory postsynaptic potential was blocked by bicuculline (30 microM), a GABA(A) receptor antagonist. High frequency stimulation produced long-term potentiation of the excitatory postsynaptic potential in the Mg(2+)-free solution containing bicuculline. When the fast and slow inhibitory postsynaptic potentials were blocked by GABA(A) and GABA(B) receptor antagonists (bicuculline and CGP 55845A respectively), high frequency stimulation produced a large and sustained depolarization followed by long-term potentiation of the excitatory postsynaptic potential. However, the excitatory postsynaptic potential was not enhanced by administration of these drugs after termination of high frequency stimulation. Pretreatment with 2-amino-5-phosphonopentanoate, a NMDA receptor antagonist, resulted in loss of long-term potentiation in both sets of experiments. Paired-pulse stimulation of the hippocampal CA3 region with interstimulus intervals between 200 and 800 ms depressed the second excitatory postsynaptic potential in the presence of bicuculline. CGP 35348, a GABA(B) receptor antagonist, reversed the depression of excitatory postsynaptic potentials to facilitation. These data suggest that high frequency stimulation of hippocampal CA3 neurons enhances the efficacy of GABAergic inhibitory circuits which, in turn, depress the ability of lateral septal nucleus neurons to express long-term potentiation.
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PMID:Activation of inhibitory pathways suppresses the induction of long-term potentiation in neurons of the rat lateral septal nucleus. 1167 2

Cyclical activity of GABAergic interneurons during theta rhythm could mediate phasic changes in strength of glutamatergic synaptic transmission in the hippocampal formation if presynaptic inhibition from activation of GABA(B) receptors is sufficiently rapid to change within a theta cycle. The experiments described here analyzed the time course of GABA(B) modulation using a heterosynaptic depression paradigm in anesthetized rats at physiological temperatures. Heterosynaptic depression of the slope of evoked potentials decayed with a time constant that would allow significant changes in transmission across different phases of the theta cycle. This heterosynaptic depression was significantly reduced by local infusion of the GABA(B) receptor antagonist CGP55845A.
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PMID:GABA(B) presynaptic inhibition has an in vivo time constant sufficiently rapid to allow modulation at theta frequency. 1187 93

The mesolimbic dopamine (DA) system originating in the ventral tegmental area (VTA) is involved in many drug-related behaviors, including ethanol self-administration. In particular, VTA activity regulating ethanol consummatory behavior appears to be modulated through GABA(A) receptors. Previous exposure to ethanol enhances ethanol self-administration, but the mechanisms underlying this phenomenon are not well understood. In this study, we examined changes occurring at GABA synapses onto VTA DA neurons after a single in vivo exposure to ethanol. We observed that evoked GABA(A) IPSCs in DA neurons of ethanol-treated animals exhibited paired-pulse depression (PPD) compared with saline-treated animals, which exhibited paired-pulse facilitation (PPF). Furthermore, PPD was still present 1 week after the single exposure to ethanol. An increase in frequency of spontaneous miniature GABA(A) IPSCs (mIPSCs) was also observed in the ethanol-treated animals. Additionally, the GABA(B) receptor antagonist (3-aminopropyl)(diethoxymethyl) phosphinic acid shifted PPD to PPF, indicating that presynaptic GABA(B) receptor activation, likely attributable to GABA spillover, might play a role in mediating PPD in the ethanol-treated mice. The activation of adenylyl cyclase by forskolin increased the amplitude of GABA(A) IPSCs and the frequency of mIPSCs in the saline- but not in the ethanol-treated animals. Conversely, the protein kinase A (PKA) inhibitor N-[z-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide significantly decreased both the frequency of spontaneous mIPSCs and the amplitude of GABA(A) IPSCs in the ethanol-treated mice but not in the saline controls. The present results indicate that potentiation of GABAergic synapses, via a PKA-dependent mechanism, occurs in the VTA after a single in vivo exposure to ethanol, and such potentiation might be a key synaptic modification underlying increased ethanol intake.
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PMID:Long-lasting potentiation of GABAergic synapses in dopamine neurons after a single in vivo ethanol exposure. 1189 47

1. The modulatory effects of mGlu receptors on NMDA-induced potential changes in spinal motoneurones were studied in vitro. 2. Selective activation of mGlu5 receptors by 10 microM (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG; EC(50)=280 +/- 24 microM) did not produce any change in the ventral root potential. However, the same concentration of CHPG (10 min perfusion) significantly attenuated the NMDA-induced ventral root depolarization (VRD). The effect persisted for 10 min after washout. NMDA-induced responses returned to control in 30 min. Brief co-application of CHPG and NMDA did not alter the NMDA-induced response indicating lack of direct receptor interaction. 3. The attenuating effect of CHPG on the NMDA-induced VRD was inhibited by the mGluR5 receptor antagonist, 2-methyl-6-phenyl-ethynylpyridine (MPEP). 4. In the presence of CGP56433A, a GABA(B) receptor antagonist, the NMDA-induced VRD was unchanged. However, NMDA-induced responses were potentiated after 10 min co-application of CHPG and CGP56433A. 5. (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R,4R)-APDC), a group II mGlu receptor agonist did not attenuate the NMDA-induced response. 6. Under normal physiological conditions group I mGlu receptor agonists activate at least two populations of neurones: (1) GABA-ergic cells, which could release GABA and inhibit dorsal horn neurones, and (2) deep dorsal horn neurones/motoneurones which express NMDA receptors. Therefore, activation of mGlu5 receptors located on GABA-ergic interneurones could influence any direct potentiating interaction between mGlu5 and NMDA receptors in spinal cord and result in depression of the VRD. In the presence of a GABA(B) receptor antagonist, the direct synergistic interaction is unmasked. These data suggest that group I mGlu receptors provide a complex modulation of spinal synaptic processes.
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PMID:Interaction of group I mGlu and NMDA receptor agonists within the dorsal horn of the spinal cord of the juvenile rat. 1201 Jul 73


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