The European journal of neuroscience
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Contactin, a glycosyl-phosphatidylinositol (GPI)-anchored predominantly neuronal cell surface glycoprotein, associates with sodium channels Nav1.2, Nav1.3 and Nav1.9, and enhances the density of these channels on the plasma membrane in mammalian expression systems. However, a detailed functional analysis of these interactions and of untested putative interactions with other sodium channel isoforms in mammalian neuronal cells has not been carried out. We examined the expression and function of sodium channels in small-diameter dorsal root ganglion (DRG) neurons from contactin-deficient (CNTN-/-) mice, compared to CNTN+/+ litter mates. ⋯ Contactin's effect was selective for IB4+ neurons as current densities for both TTX-R and TTX-S channels were not significantly different in IB4- DRG neurons from the two genotypes. Consistent with these results, we have demonstrated a reduction in Nav1.8 and Nav1.9 immunostaining on peripherin-positive unmyelinated axons in sciatic nerves from CNTN-/- mice but detected no changes in the expression for the two major TTX-S channels Nav1.6 and Nav1.7. These data provide evidence of a role for contactin in selectively regulating the cell surface expression and current densities of TTX-R but not TTX-S Na+ channel isoforms in nociceptive DRG neurons; this regulation could modulate the membrane properties and excitability of these neurons.
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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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The aim of the present study was to investigate the spinal cord effects and sites of action of different inhaled concentrations (0.5-2%) of the anaesthetic, halothane. Simultaneous recordings were made of 3 Hz, suprathreshold (1.5 x T) electrically evoked spinal dorsal horn (DH) wide-dynamic range (WDR) neuron responses and of single motor unit (SMU) electromyographic (EMG) responses underlying the spinal withdrawal reflex in spinalized Wistar rats. Compared with the baseline responses obtained with 0.5% halothane, the electrically evoked early responses of the DH WDR neurons as well as the SMUs were only depressed by the highest, 2% concentration of halothane. ⋯ The inhibitory effects of 2% halothane on the early and the late responses of the DH WDR neurons, but not of the SMUs, were completely reversed by opioid micro-receptor antagonist naloxone (0.04 mg/kg). However, no significant effects of naloxone were found on different responses of the DH WDR neurons as well as the SMUs at 0.5-1% halothane, suggesting that different concentrations of halothane may modulate different spinal receptors. We conclude that halothane at high concentrations (1.5-2%) seems to play a predominant inhibitory role via spinal multireceptors on ventral horn (VH) motor neurons, and less on DH sensory WDR neurons, of the spinal cord.
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Memory impairments, which occur regularly across species as a result of ageing, disease (such as diabetes mellitus) and psychological insults, constitute a useful area for investigating the neurobiological basis of learning and memory. Previous studies in rats found that induction of diabetes (with streptozotocin, STZ) impairs long-term potentiation (LTP) but enhances long-term depression (LTD) induced by high- (HFS) and low-frequency stimulations (LFS), respectively. Using a pairing protocol under whole-cell recording conditions to induce synaptic plasticity at Schaffer collateral synapses in hippocampal CA1 slices, we show that LTD and LTP have similar magnitudes in diabetic and age-matched control rats. ⋯ In addition, compared with naïve synapses, prior induction of LTP produces a 10 mV leftward shift in Vms for inducing subsequent LTD in control but not in diabetic rats. This could indicate that diabetes acts on synaptic plasticity through mechanisms involved in metaplasticity. Persistent facilitation of LTD and inhibition of LTP may contribute to learning and memory impairments associated with diabetes mellitus.