The European journal of neuroscience
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Comparative Study
Selective sparing of hippocampal CA3 cells following in vitro ischemia is due to selective inhibition by acidosis.
A brief global ischemic insult to the brain leads to a selective degeneration of the pyramidal neurons in the hippocampal CA1 region while the neurons in the neighbouring CA3 region are spared. The reason for this difference is not known. The selective vulnerability of CA1 neurons to ischemia can be reproduced in vitro in murine organotypic slice cultures, if the ion concentrations in the medium during the anoxic/aglycemic insult are similar to that in the brain extracellular fluid during ischemia in vivo. ⋯ Patch-clamp recordings from pyramidal neurons in the CA1 and CA3 regions, respectively, revealed a pronounced inhibition of NMDA-receptor mediated excitatory postsynaptic currents (EPSCs) at pH 6.5 that was equally pronounced in the two regions. However, when changing pH from 6.5 to 7.4 the recovery of the EPSCs was significantly slower in the CA3 region. We conclude that acidosis selectively protects CA3 pyramidal neurons during in vitro ischemia, and differentially affects the kinetics of NMDA receptor activation, which may explain the difference in vulnerability between CA1 and CA3 pyramidal neurons to an ischemic insult.
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It is well-established that light pulses regulate components of the extracellular signal-regulated kinases I/II (ERK) cascade in the suprachiasmatic nuclei (SCN) circadian clock. These events are important for photic-resetting of the circadian clock. The SCN circadian clock is also reset by pulses of dark, but it is unknown if this stimulus alters the activity of ERK, the transcription factor Elk-1 or expression of the immediate early gene c-fos in the SCN. ⋯ When given at the beginning of the subjective night (CT13), a 6-h dark pulse did not phase-shift behavioural rhythms and failed to alter the expression of c-Fos, P-ERK, or P-Elk-1 in the SCN. At the level of the visual thalamus, expression of c-Fos in the intergeniculate leaflet was higher during the subjective night as compared to the subjective day, although dark pulses had no robust effects on expression of c-Fos or P-ELK-1 in this structure. We conclude that dark-pulse resetting of the circadian clock is complex and involves both non-photic and photic components.
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Comparative Study
Inhibitory effects of CB1 and CB2 receptor agonists on responses of DRG neurons and dorsal horn neurons in neuropathic rats.
Cannabinoid 2 (CB2) receptor mediated antinociception and increased levels of spinal CB2 receptor mRNA are reported in neuropathic Sprague-Dawley rats. The aim of this study was to provide functional evidence for a role of peripheral, vs. spinal, CB2 and cannabinoid 1 (CB1) receptors in neuropathic rats. Effects of the CB2 receptor agonist, JWH-133, and the CB1 receptor agonist, arachidonyl-2-chloroethylamide (ACEA), on primary afferent fibres were determined by calcium imaging studies of adult dorsal root ganglion (DRG) neurons taken from neuropathic and sham-operated rats. ⋯ Spinal ACEA inhibited mechanically evoked responses of neuropathic and sham-operated rats, these effects were blocked by SR141716A (0.01 microg/50 microL). Our data provide evidence for a functional role of CB2, as well as CB1 receptors on DRG neurons in sham and neuropathic rats. At the level of the spinal cord, CB2 receptors have inhibitory effects in neuropathic, but not sham-operated rats suggesting that spinal CB2 may be an important analgesic target.
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Comparative Study
Roles of NMDA receptor NR2A and NR2B subtypes for long-term depression in the anterior cingulate cortex.
The anterior cingulate cortex (ACC) is thought to be important for the establishment, consolidation and retrieval of permanent memory. In many brain regions, including the hippocampus, it is suggested that long-term potentiation (LTP) and long-term depression (LTD), the cellular mechanisms for learning and memory, require the activation of glutamate N-methyl-D-aspartate receptors (NMDARs). In the hippocampus, the NR2A subunit is believed to be involved in the induction of LTP, whereas the NR2B subunit contributes to the formation of LTD. ⋯ Here we show that LTD can be induced by the combination of presynaptic stimulation with postsynaptic depolarization ('pairing training') in adult mouse ACC neurons. This form of LTD is an NMDAR- and voltage-dependent mechanism and a postsynaptic Ca2+ increase is required for the induction of LTD. Furthermore, our studies provide direct physiological evidence that both NR2A and NR2B subunits are involved in the induction of LTD in the ACC.
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Comparative Study
Increased measures of anxiety and weight gain in mice lacking the group III metabotropic glutamate receptor mGluR8.
To study the role of the metabotropic glutamate receptor 8 (mGluR8), mice lacking this receptor were generated by homologous recombination. Homozygous mGluR8-deficient mice are about 8% heavier than their wild-type age-matched controls after reaching 4 weeks of age. This weight difference is not caused by an altered food intake and is not exacerbated by feeding the animals a high-fat diet. ⋯ By contrast, there were no genotype differences in locomotor activity in the open field, plus maze, or in total time spent exploring objects during object recognition tests, indicating that there is a dissociation between effects of mGluR8 deficiency in exploratory activity in a novel safe enclosed environment vs. a more anxiogenic novel open environment. The absence of mGluR8 also leads to increased measures of anxiety in the open field and elevated plus maze. Whether the diverse phenotypic differences observed in mGluR8-/- mice result from the misregulation of a unique neural pathway, possibly in the thalamus or hypothalamus, or whether they are the consequence of multiple developmental and functional alterations in synaptic transmission, remains to be determined.