Synapse
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Comparative Study
Comparison of paired-pulse facilitation of AMPA and NMDA synaptic currents in the lateral amygdala.
Stimulating thalamic fibers exiting from the internal capsule evokes a glutamatergic excitatory postsynaptic current (EPSC) recorded in vitro with patch electrodes in neurons of the rat lateral amygdala (LA). The purpose of this study is to compare paired-pulse facilitation (PPF), a form of short-term synaptic plasticity, of AMPA and NMDA receptor-mediated EPSCs. Analysis of PPF at this synapse is important since, in fear-conditioned animals, PPF reflects an enhanced transmitter release but the amplitude of only AMPA EPSCs is facilitated. ⋯ In contrast, NMDA PPF was dependent on stimulus intensity and postsynaptic voltage and the amplitudes of paired NMDA EPSCs had a positive correlation, suggesting a postsynaptic influence. Both AMPA and NMDA PPF were influenced by GABA inhibition and this could be a factor in the magnitude disparity. These data show that AMPA and NMDA PPF have different characteristics and contribute to the composite PPF in the thalamic to lateral amygdala pathway.
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Rat bilateral olfactory bulbectomy (OBX) serves as a useful model in the study of depression and the mechanisms of action of antidepressant treatments. Considering the evidence of NMDA receptors involvement in depression, the present study was undertaken in order to investigate the time-course effects of OBX on the NMDA receptor function. Following bilateral olfactory bulbectomy, rats display an increase in locomotor activity and changes in other types of behavior in a novel environment. ⋯ This challenge is known to induce hyperlocomotion and a number of stereotypies in naive rats. These effects were drastically reduced in OBX as compared to sham-operated rats. These data are consistent with the above-mentioned decrease in cerebral binding of MK-801 to NMDA receptors.
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Altered glutamatergic transmission in the striatum may be implicated in behavioral sensitization to repeated amphetamine (AMPH) administration. Quantitative in situ hybridization histochemistry was performed to define the effects of acute and chronic AMPH exposures on mRNA expression of Group I metabotropic glutamate receptors (mGluRs) in the striatum. Behavioral ratings indicated that the motor activity of rats was significantly higher after the final of five daily AMPH injections (4 mg/kg, i.p.) than that after the first of five daily AMPH, indicative of the development of behavioral sensitization. ⋯ The reduction persisted at 7, 14, and 28 days of withdrawal. These results reveal a close linkage between striatal Group I mGluR gene expression and behavioral sensitization to AMPH. This may indicate functional implications of the two subtypes of Group I mGluRs in the regulation of behavioral sensitization to the dopamine stimulant.
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Ampakines are small benzamide compounds that allosterically produce the positive modulation of AMPA receptors and improve performance on a variety of behavioral tasks. To test if the native synaptic membrane is necessary for the effects of such positive modulators, the mechanism of action of the Ampakine 1-(1,3-benzodioxol-5-ylcarbonyl)-1,2,3,6-tetrahydropyridine (CX509) was investigated in isolated rat brain AMPA receptors reconstituted in lipid bilayers. The drug increased the open time of AMPA-induced single channel current fluctuations with an EC(50) of 4 microM. ⋯ In fact, CX509 was about 100 times more potent on the reconstituted AMPA receptors than on receptors in their native membrane. These findings indicate that centrally active Ampakines modulate specific kinetic properties of AMPA currents. They also raise the possibility that AMPA receptors are regulated by factors present in situ, thus explaining the more efficient modulatory effects of CX509 when acting on receptors removed from their synaptic location.
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The subthalamic nucleus (STN) receives dopaminergic projections from the substantia nigra pars compacta (SNc). To investigate the role of direct and indirect dopaminergic influences on STN neurons, the spontaneous activity was studied in four groups of animals: normal rats, rats with intrasubthalamic or intranigral injection of 6-hydroxydopamine (6-OHDA), and sham STN injection rats by using extracellular recordings 4 weeks postsurgery. After intrasubthalamic injection of 6-OHDA, the mean firing rate significantly decreased (7.29 +/- 0.39 spikes/sec, P < 0.01 vs. 11.13 +/- 0.59 spikes/sec in normal or 11.26 +/- 0.57 spikes/sec in sham group), and the percentage of STN neurons discharging regularly decreased significantly (81%, P < 0.05 vs. 90% in normal group or P < 0.01 vs. 92% in sham group) and that of bursty cells increased (19%, P < 0.05 vs. 10%; in normal group or P < 0.01 vs. 8% in sham group). ⋯ However, the firing pattern was dramatically changed: 74% of cells exhibited bursty pattern and only 26% of cells discharged regularly or slightly irregularly. Immunohistochemical results showed that intrasubthalamic injection of 6-OHDA induced a marked degeneration of dopaminergic cells in the lateral part of the ipsilateral SNc, whereas 6-OHDA injection into the SNc induced a total in situ lesion of dopamine cells. These results suggest that the SNc exerts an excitatory influence on STN neurons and that the loss of this dopaminergic projection could, at least partially, account for the changes in the firing pattern of STN neurons in the 6-OHDA rat model of parkinsonism.