Journal of neurophysiology
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Activation of neurons in the midbrain periaqueductal gray (PAG) inhibits spinal dorsal horn neurons and produces behavioral antinociception in animals and analgesia in humans. Although dorsal horn regions modulated by PAG activation contain all three opioid receptor classes (mu, delta, and kappa), as well as enkephalinergic interneurons and terminal fields, descending opioid-mediated inhibition of dorsal horn neurons has not been demonstrated. We examined the contribution of dorsal horn mu-opioid receptors to the PAG-elicited descending modulation of nociceptive transmission. ⋯ A similar effect was produced by naloxone; however, naloxone had an excitatory influence on dorsal horn neurons in the absence of PAG-evoked descending inhibition. This is the first demonstration that endogenous opioids acting via spinal mu-opioid receptors contribute to brain stem control of nociceptive spinal dorsal horn neurons. The inhibition appears to result in part from presynaptic inhibition of afferents to dorsal horn neurons.
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In vitro slice experiments were undertaken in adult rats to investigate the physiological origins of a chronic epileptic condition that was initiated in infancy. A unilateral injection of a minute quantity of tetanus toxin into hippocampus on postnatal day 10 produced a severe convulsive syndrome characterized by brief but repeated seizures that lasted for 5-7 days. Hippocampal slices were then taken from these rats in adulthood because at this time previous studies have shown the occurrence of electrographic and behavioral seizures. ⋯ In contrast, slices from control rats produced only brief 100-ms network bursts. These results suggest that a change in excitability within CA3C recurrent excitatory networks likely contributes to seizures in chronically epileptic rats. However, at the same time, this hyperexcitability is controlled to an important degree by functional GABAA-mediated synaptic inhibition.
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Ionic mechanisms underlying low-threshold (LTO) and high-threshold (HTO) oscillations occurring in a class of spiny neurons within the basolateral amygdaloid complex (see companion paper) were investigated in slice preparations of the guinea pig amygdala in vitro. LTOs were abolished through local application of tetrodotoxin (TTX, 10-20 microM) or a decrease in the extracellular sodium concentration ([Na+]o) from 153 to 26 mM, whereas HTOs were more readily elicited under these conditions. The effects of TTX and low [Na+]o were accompanied by a hyperpolarizing shift of the membrane potential by 3 +/- 1 mV and a decrease in apparent input resistance by 14 +/- 11 MOmega. ⋯ It is concluded that a TTX-sensitive Na+ conductance and the M current contribute to generation of the LTOs, although their exact role in rhythmogenesisremains to be determined. HTOs seem to largely depend on a functional coupling between high-voltage-activated Ca2+ conductances, a Ca2+-activated K+ current presumably carried through BKCa channels, and additional voltage-dependent K+ conductances. In functional terms, the HTOs are important in determining spike frequency adaptation toward a slow-rhythmic firing pattern during maintained depolarizing influence.
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We evaluated the role of the sodium/glutamate transporter at the synaptic terminals of cone photoreceptors in controlling postsynaptic response kinetics. The strategy was to measure the changes in horizontal cell response rate induced by blocking transporter uptake in cones with dihydrokainate (DHK). DHK was chosen as the uptake blocker because, as we show through autoradiographic uptake measurements, DHK specifically blocked uptake in cones without affecting uptake in Mueller cells. ⋯ This suggests that the transporter was both voltage dependent and robust enough to modulate glutamate concentration. The transporter must be at least as effective as diffusion in removing glutamate from the synapse because there is only a very small light response once the transporter is blocked. The transporter, via its voltage dependence on cone membrane potential, appears to contribute significantly to the control of postsynaptic response kinetics.
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We studied the effects of activation of the metabotropic glutamate receptors on intrinsic currents of magnocellular n urons of the supraoptic nucleus (SON) with whole cell patch-clamp and conventional intracellular recordings in coronal slices (400 micron) of the rat hypothalamus. Trans-(+/-)-1-amino-1,3-cyclopentane dicarboxylic acid (trans-ACPD, 10-100 microM), a broad-spectrum metabotropic glutamate receptor agonist, evoked an inward current (18.7 +/- 3.45 pA) or a slow depolarization (7.35 +/- 4.73 mV) and a 10-30% decrease in whole cell conductance in approximately 50% of the magnocellular neurons recorded at resting membrane potential. The decrease in conductance and the inward current were caused largely by the attenuation of a resting potassium conductance because they were reduced by the replacement of intracellular potassium with an equimolar concentration of cesium or by the addition of potassium channel blockers to the extracellular medium. ⋯ A group II receptor agonist, 2S,1'S,2'S-2carboxycyclopropylglycine and a group III receptor agonist, (+)-2-amino-4-phosphonobutyric acid, had no effect on the resting or voltage-gated K+ currents, indicating that the reduction of K+ currents was mediated by group I receptors. About 80% of the SON cells that were labeled immunohistochemically for vasopressin responded to metabotropic glutamate receptor activation, whereas only 33% of labeled oxytocin cells responded, suggesting that metabotropic receptors are expressed preferentially in vasopressinergic neurons. These data indicate that activation of the group I metabotropic glutamate receptors leads to an increase in the postsynaptic excitability of magnocellular neurons by blocking resting K+ currents as well as by reducing voltage-gated and Ca2+-activated K+ currents.