Neuroscience
-
The majority of neurons in the magnocellular basal forebrain are wakefulness-active with highest discharge activity during wakefulness and a marked reduction in activity just before and during the entry to non-rapid eye movement (REM) sleep. We have hypothesized that the reduction of discharge activity of wakefulness-active neurons and a consequent facilitation of the transition from wakefulness to sleep is due to an increase in the extracellular concentration of adenosine during wakefulness. To test the hypothesis, the present study employed microdialysis perfusion of adenosinergic pharmacological agents combined with single unit recording in freely moving cats, so as to determine: 1). if there were dose-dependent effects on behaviorally identified wakefulness-active neurons; 2). whether effects were mediated by the A1 receptor, as contrasted to the A2a receptor; and 3). if effects were specific to wakefulness-active neurons, and not present in sleep-active neurons, those preferentially discharging in nonREM sleep. ⋯ The A1 receptor antagonist 8-cyclopentyl-1-3-dimethylxanthine increased the discharge of wakefulness-active neurons (n=5), but the A2a receptor agonist, CGS-16284, had no effect (n=3). Recording sites were histologically localized to the cholinergic basal forebrain. These data support our hypothesis that adenosine acts via the A1 receptor to reduce the activity of wakefulness-promoting neurons, thus providing a cellular mechanism explaining why the increased adenosine concentrations observed in the basal forebrain following prolonged wakefulness act to induce sleep.
-
Comparative Study
A combined blockade of glycine and calcium-dependent potassium channels abolishes the respiratory rhythm.
In order to test whether glycinergic inhibition is essential for the in vivo respiratory rhythm, we analysed the discharge properties of neurones in the medullary respiratory network after blockade of glycine receptors in the in situ perfused brainstem preparation of mature wild type and oscillator mice with a deficient glycine receptor. In wild type mice, selective blockade of glycine receptors with low concentrations of strychnine (0.03-0.3 microM) provoked considerable changes in neuronal discharge characteristics: The cycle phase relationship of inspiratory, post-inspiratory and expiratory specific patterns of membrane potential changes was altered profoundly. Inspiratory, post-inspiratory and expiratory neurones developed a propensity for fast voltage oscillations that were accompanied by multiple burst discharges. ⋯ In contrast, rhythmic activity was only weakened, but preserved after the "small" Ca2+-dependent activated K+ conductance was blocked with apamin (8 nM). Also low concentrations of pentobarbital sodium (6 mg/kg) abolished rhythmic respiratory activity after blockade of glycine receptors in the wild type mice and in glycine receptor deficient oscillator mice. The data imply that failure of glycine receptors provokes enhanced bursting behaviour of respiratory neurones, whilst the additional blockade of BKCa channels by charybdotoxin or with pentobarbital abolishes the respiratory rhythm.
-
The effect of food hardness during mastication on nociceptive transmission in the spinal cord was studied by analyzing complete Freund's adjuvant (CFA) induced nocifensive behavior and Fos expression. The behavioral study showed that the shortening of the withdrawal latency following CFA injection into the hind paw was depressed after a change in the given food hardness from soft to hard. The depression of nocifensive behavior in the rats with hard food was reversed after i.v. injection of naloxone. ⋯ Furthermore, the depression of Fos protein-LI cells following hard food intake was significantly inhibited after bilateral inferior alveolar nerve transection or bilateral ablation of the somatosensory cortex. These findings suggest that the change in food hardness during mastication might drive an opioid descending system through the trigeminal sensory pathway and somatosensory cortex resulting in an antinociceptive effect on chronic pain. However, IAN transection and cortical ablation did not induce 100% reversal of Fos expression, suggesting other than trigeminal sensory system may be involved in this phenomena, such as the pathway through the brainstem reticular formation.
-
Comparative Study
Highly differential expression of the monocarboxylate transporters MCT2 and MCT4 in the developing rat brain.
Monocarboxylate transporters (MCTs) play an important role in the metabolism of all cells. They mediate the transport of lactate and pyruvate but also some other substrates such as ketone bodies. It has been proposed that glial cells release monocarboxylates to fuel neighbouring neurons. ⋯ In contrast to MCT2, MCT4 is exclusively present in astroglia during all stages of development. Furthermore, MCT4 expression is very low at birth and reaches adult level by P14. Our results are consistent with previous data suggesting that in the immature brain much of the energy demand is met by monocarboxylates and ketone bodies.
-
Comparative Study
Gender differences in the regulation of 3 alpha-hydroxysteroid dehydrogenase in rat brain and sensitivity to neurosteroid-mediated stress protection.
The enzyme 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) is involved in the generation of neuroactive steroids through ring-A-reduction of hormonal precursors. We examined the developmental regulation of, gender differences in, and effects of hormonal manipulations on the expression of 3 alpha-HSD in the rat hippocampus. High levels of 3 alpha-HSD mRNA were found on postnatal day 7, coinciding with the stress hyporesponsive period in the rat. ⋯ Males are liable to aftereffects of neonatal maternal deprivation, regardless of their adult gonadal status. In females, however, anxiogenic aftereffects of neonatal stress become apparent only after gonadectomy. These data suggest that (i) transient increase of neurosteroid biosynthesis may contribute to stress hyporesponsiveness during early infancy; (ii) gonadal steroids regulate 3 alpha-HSD expression in the hippocampus in a sex-specific mode; (iii) physiological sex steroid secretions in females may mask behavioral consequences of adverse early life events, and (iv) concomitant treatment with the neurosteroid THP counteracts behavioral and endocrine dysregulation induced by neonatal stress in both genders.