Neuroscience
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Comparative Study
Desynchronisation of spontaneously recurrent experimental seizures proceeds with a single rhythm.
Here we investigate the temporal properties of recurrent seizure-like events (SLEs) in a low-[Mg(2+)] model of experimental epilepsy. Simultaneous intra- and extracellular electric signals were recorded in the CA3 region of rat hippocampal slices whereby cytosolic [Ca(2+)] transients were imaged by fluorescence detection. Recurrence pattern analysis was applied to give a measure of synchrony of simultaneously recorded intra- and extracellular electric signals and the SLE frequencies were extracted by complex wavelet analysis. ⋯ Release of gap junction blockade shortened both SLEs and their tonic phase indicating that persistent changes occurred via an altered gap junction coupling. We conclude that the initially precise temporal synchrony is gradually destroyed during ictal events with a single rhythm of continuously decreasing frequency. Blockade of gap junction coupling might prevent epileptic synchronisation.
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Comparative Study
[3H]-nociceptin ligand-binding and nociceptin opioid receptor mrna expression in the human brain.
Following the cloning of the novel nociceptin opioid receptor (NOP(1)) and the identification of its endogenous ligand orphanin FQ/nociceptin the distribution and functional role of the NOP(1) receptor system have been studied mainly in the rodent CNS. In the present study the regional distribution and splice variant expression of the NOP(1) receptor was investigated in the adult human brain using [(3)H]-nociceptin autoradiography, NOP(1) reverse transcriptase PCR and mRNA in situ hybridization. Ligand binding revealed strong expression of functional NOP(1) receptors in the cerebral cortex and moderate signals in hippocampus and cerebellum. ⋯ A considerable expression of N-terminal NOP(1) splice variant mRNAs was not detectable in the human brain by means of in situ hybridization. This suggests that functional NOP(1) receptors in the human brain are encoded by N-terminal full length NOP(1) transcripts. The present data on the anatomical distribution of nociceptin binding sites and NOP(1) receptor mRNA contribute to the knowledge about opioid receptor systems in the human brain and may promote the understanding of function and pharmacology of the orphanin FQ/nociceptin receptor system in the human CNS.
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Comparative Study
Neuronal activity regulates GABAA receptor subunit expression in organotypic hippocampal slice cultures.
The postnatal expression of GABA(A) receptor subunit mRNAs in the rat brain, including the hippocampus, exhibits a unique temporal and regional developmental profile in vivo, which may be altered by external stimuli. Using the in situ hybridization technique we have now studied the in vitro expression of alpha1,alpha2, alpha 4, alpha 5, beta 1, beta 3, gamma 2, and gamma 3 subunit mRNAs of GABA(A) receptors in organotypic hippocampal slices cultured for 7 days. To find out whether neuronal activity regulates the subunit expression, a subset of cultures was chronically treated either with a GABA(A) receptor antagonist picrotoxin, or by a non-N-methyl-D-aspartate (non-NMDA)-receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). ⋯ In picrotoxin-treated cultures, the expression of alpha1, alpha 5 and gamma 2 mRNAs was significantly increased in pyramidal cell layers, and in DNQX-treated cultures the expression of alpha2 mRNA in CA3c and DG, and that of beta1 in DG. Changes in the expression of GABA(A) receptor subunit mRNAs in treated cultures suggest that neuronal activity can regulate their regional expression in vitro. Since the expression profile in untreated control cultures closely resembled that observed earlier in vivo, organotypic hippocampal slice cultures could serve as a good model system to study the regulatory mechanisms of receptor expression under well-controlled experimental conditions in the developing hippocampus.
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Comparative Study
Effects of extracellular atp on axonal transport in cultured mouse dorsal root ganglion neurons.
In primary sensory neurons, extracellular ATP plays important roles in nociception and afferent neurotransmission. Here we investigated the effects of ATP on axonal transport in cultured adult mouse dorsal root ganglion neurons using video-enhanced microscopy. Continuous application (26 min) of ATP (100 microM) significantly increased axonal transport of membrane-bound organelles in anterograde and retrograde directions. ⋯ Our findings indicate that extracellular ATP is able to increase axonal transport in primary sensory neurons. The equal potency of ATP and UTP with no detectable response to ADP, alpha,beta-methylene ATP, or 2-methylthio ATP suggests the possible involvement of P2Y(2) receptors. Extracellular ATP may play an important role in the modulation of axonal transport in sensory neurons.
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The effects of repeated administration of a tricyclic antidepressant, imipramine, and a selective serotonin reuptake blocker, citalopram, for 14 days (10 mg/kg p.o., twice daily), were studied ex vivo in rat frontal cortex slices prepared 48 h after last dose of the drug. Treatment with both antidepressants resulted in a decrease in the amplitude of field potentials evoked in layer II/III by stimulation of underlying sites in layer V. The amplitude ratio of pharmacologically isolated N-methyl-D-aspartic acid (NMDA) to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor-mediated components of the field potential was reduced. These results indicate that chronic treatment with imipramine or citalopram results in an attenuation of glutamatergic synaptic transmission in the cerebral cortex.