A resonant sextuplet of sub-Neptunes transiting the bright star HD 110067.

Planets with radii between that of the Earth and Neptune (hereafter referred to as 'sub-Neptunes') are found in close-in orbits around more than half of all Sun-like stars1,2. However, their composition, formation and evolution remain poorly understood3. The study of multiplanetary systems offers an opportunity to investigate the outcomes of planet formation and evolution while controlling for initial conditions and environment. Those in resonance (with their orbital periods related by a ratio of small integers) are particularly valuable because they imply a system architecture practically unchanged since its birth. Here we present the observations of six transiting planets around the bright nearby star HD 110067. We find that the planets follow a chain of resonant orbits. A dynamical study of the innermost planet triplet allowed the prediction and later confirmation of the orbits of the rest of the planets in the system. The six planets are found to be sub-Neptunes with radii ranging from 1.94R⊕ to 2.85R⊕. Three of the planets have measured masses, yielding low bulk densities that suggest the presence of large hydrogen-dominated atmospheres.

Thermal tolerance and potential distribution of Carvalhotingis visenda (Hemiptera: Tingidae), a biological control agent for cat's claw creeper, Macfadyena unguis-cati (Bignoniaceae).

The specialist tingid, Carvalhotingis visenda, is a biological control agent for cat's claw creeper, Macfadyena unguis-cati (Bignoniaceae). Cat's claw creeper is an invasive liana with a wide climatic tolerance, and for biological control to be effective the tingid must survive and develop over a range of temperatures. We evaluated the effect of constant temperatures (0-45 degrees C) on the survival and development of C. visenda. Adults showed tolerance for wider temperature ranges (0-45 degrees C), but oviposition, egg hatching and nymphal development were all affected by both high (>30 degrees C) and low (<20 degrees C) temperatures. Temperatures between 20 degrees C and 30 degrees C are the most favourable for adult survival, oviposition, egg hatching and nymphal development. The ability of adults and nymphs to survive for a few days at high (40 degrees C and 45 degrees C) and low (0 degrees C and 5 degrees C) temperatures suggest that extreme temperature events, which usually occur for short durations (hours) in cat's claw creeper infested regions in Queensland and New South Wales states are not likely to affect the tingid population. The potential number of generations (egg to adult) the tingid can complete in a year in Australia ranged from three to eight, with more generations in Queensland than in New South Wales.

Children of parents who have been hospitalised with psychiatric disorders are at risk of poor school readiness.

AIMS.: Children of parents with psychiatric disorders are at risk of poor outcomes. However, there is limited evidence regarding the relationship between parental psychiatric disorders and child school readiness, which is linked to later academic achievement. This study aims to investigate these relationships and broaden the evidence underlying the rationale for family-focused interventions for parental psychiatric disorders. METHOD.: This study used linked administrative data. Children's school readiness in multiple developmental domains (physical, social, emotional, communicative, cognitive) was measured by the Australian Early Development Census (AEDC) for 19 071 Western Australian children (mean age 5.5 years). Children scoring in the bottom 25% on any AEDC domain were considered developmentally vulnerable, or at risk of vulnerability, on that domain. Biological child-parent pairs were identified using birth records. Parents with psychiatric disorders were identified from hospital records, which included information on diagnosis and frequency/duration of psychiatric admissions. Logistic regressions, adjusted for parent age, mother's marital status, child Aboriginality, child English language status, local community remoteness and socioeconomic index, estimated the odds of children being vulnerable/at-risk on each of the AEDC domains. RESULTS.: A total of 719 mothers and 417 fathers had a psychiatric hospitalisation during the study period (12 months prior to the child's birth, up to the end of 2009). Children whose parents had psychiatric disorders had increased odds of being classified as vulnerable/at-risk for school readiness. This increase in odds was evident for both maternal (adjusted odds ratio, aOR 1.37- 1.51) and paternal psychiatric disorders (aOR 1.38-1.50); and for a single admission of one day (aOR 1.32-1.59), a single admission of multiple days (aOR 1.30-1.47), and multiple admissions (aOR 1.35-1.63). Some variability in child outcome was found depending on the parents' psychiatric diagnosis (mood, anxiety, substance abuse or comorbid disorder). CONCLUSIONS.: Children of parents who have been hospitalised with psychiatric disorders are at risk for poor school readiness. These findings add support to recommendations that mental health professionals consider dependent children in discharge and treatment planning for adult psychiatric inpatients. It is also important to ensure that the impact of psychiatric illness in fathers is not overlooked in assessment and intervention. Family-based approaches to adult psychiatric care could meet the dual needs of intervention for parents and preventative measures for children. These findings can inform policy regarding the importance of integrating and coordinating services to meet the needs of families.

TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons.

Inhibition of "leak" potassium (K+) channels is a widespread CNS mechanism by which transmitters induce slow excitation. We show that TASK-1, a two pore domain K+ channel, provides a prominent leak K+ current and target for neurotransmitter modulation in hypoglossal motoneurons (HMs). TASK-1 mRNA is present at high levels in motoneurons, including HMs, which express a K+ current with pH- and voltage-dependent properties virtually identical to those of the cloned channel. This pH-sensitive K+ channel was fully inhibited by serotonin, norepinephrine, substance P, thyrotropin-releasing hormone, and 3,5-dihydroxyphenylglycine, a group I metabotropic glutamate receptor agonist. The neurotransmitter effect was entirely reconstituted in HEK 293 cells coexpressing TASK-1 and the TRH-R1 receptor. Given its expression patterns and the widespread prevalence of this neuromodulatory mechanism, TASK-1 also likely supports this action in other CNS neurons.

Validation of COBAS Taqman CT for the detection of Chlamydia trachomatis in vulvo-vaginal swabs.

BACKGROUND: Vulvo-vaginal swabs (VVSs) are not validated for use by the manufacturers of two widely used nucleic acid amplification tests (NAAT) for the detection of Chlamydia trachomatis. However, there is evidence that this type of swab is suitable for diagnosis. OBJECTIVE: To validate the Cobas Taqman CT assay for the detection of C trachomatis in VVS. METHOD: Women aged 18-24 years attending a genitourinary medicine clinic were invited to take part in the study. Participants provided a self-taken VVS and the results obtained with these samples were compared with those obtained with an endocervical swab collected by a healthcare worker. A total of 267 women took part. RESULTS: 255/267 (96%; 95% CI 92 to 98%) sets of samples gave concordant results. 12/267 (4.5%) VVSs were invalid/inhibitory and so no result was available for these samples. This compared with 2/267 (0.7%) for endocervical swabs. CONCLUSION: VVS are suitable samples for detecting C trachomatis.

Cns distribution of members of the two-pore-domain (KCNK) potassium channel family.

Two-pore-domain potassium (K(+)) channels are substrates for resting K(+) currents in neurons. They are major targets for endogenous modulators, as well as for clinically important compounds such as volatile anesthetics. In the current study, we report on the CNS distribution in the rat and mouse of mRNA encoding seven two-pore-domain K(+) channel family members: TASK-1 (KCNK3), TASK-2 (KCNK5), TASK-3 (KCNK9), TREK-1 (KCNK2), TREK-2 (KCNK10), TRAAK (KCNK4), and TWIK-1 (KCNK1). All of these genes were expressed in dorsal root ganglia, and for all of the genes except TASK-2, there was a differential distribution in the CNS. For TASK-1, highest mRNA accumulation was seen in the cerebellum and somatic motoneurons. TASK-3 was much more widely distributed, with robust expression in all brain regions, with particularly high expression in somatic motoneurons, cerebellar granule neurons, the locus ceruleus, and raphe nuclei and in various nuclei of the hypothalamus. TREK-1 was highest in the striatum and in parts of the cortex (layer IV) and hippocampus (CA2 pyramidal neurons). mRNA for TRAAK also was highest in the cortex, whereas expression of TREK-2 was primarily restricted to the cerebellar granule cell layer. There was widespread distribution of TWIK-1, with highest levels in the cerebellar granule cell layer, thalamic reticular nucleus, and piriform cortex. The differential expression of each of these genes likely contributes to characteristic excitability properties in distinct populations of neurons, as well as to diversity in their susceptibility to modulation.

Distribution and regulation by estrogen of progesterone receptor in the hypothalamus of the cat.

The diencephalon is critically involved in the estrogen-dependent receptor-mediated stimulation of respiration by progesterone in cats. To identify a neuroanatomic basis for this effect of progesterone, the diencephalon of the ovariectomized cat was examined immunohistochemically with an antiprogesterone receptor (anti-PR) monoclonal antibody. No immunostaining was found in ovariectomized animals pretreated with sesame oil alone. In contrast, numerous cells in the ventromedial aspect of the hypothalamus from cats pretreated with estradiol benzoate were PR immunoreactive. Thus, PR is induced by estrogen in hypothalamic neurons of cats. In animals pretreated with estradiol benzoate, the highest density of immunostained neurons was found throughout the infundibular nucleus, especially in the region of the mammillary recess of the third ventricle. PR-immunoreactive cells were also distributed throughout the periventricular nucleus, with the highest density located rostrally and immediately above the suprachiasmatic nucleus. Notably and in contrast to a number of other species (e.g. rat and guinea pig), only very few weakly stained PR-containing cells were found in the hypothalamic ventromedial nucleus. This latter finding could reflect the progesterone independence of sexual behaviors in cat. Overall, we have identified hypothalamic areas that may subserve estrogen-dependent receptor-mediated effects of progesterone in the cat, such as the stimulation of respiration.

The stimulation of respiration by progesterone in ovariectomized cat is mediated by an estrogen-dependent hypothalamic mechanism requiring gene expression.

The central site of action and the cellular mechanism by which progesterone stimulates respiration were studied in ovariectomized cats that were anesthetized, paralyzed, and ventilated and in which respiratory sensory feedback mechanisms were either eliminated or controlled. Phrenic nerve activity served as an index of central respiratory output. Progesterone did not stimulate respiration in ovariectomized cats not pretreated with estrogen. In contrast, repeated doses of progesterone (0.1-1.0 microgram/kg, iv, cumulative) caused a sustained (greater than 45 min) dose-dependent facilitation of phrenic nerve activity in animals primed 3 days before study with 17 beta-estradiol (20 micrograms/kg, sc). Estrogen exposure is, therefore, a prerequisite for the respiratory response to progesterone in ovariectomized cats. This estrogen-dependent respiratory response to progesterone was attenuated in animals pretreated with either the estrogen receptor antagonist CI628 or the progesterone receptor antagonist RU486, indicating that the respiratory response is mediated by both estrogen and progesterone receptors. Inhibitors of protein (anisomycin) and RNA (actinomycin-D) synthesis caused a diminution of the respiratory response to progesterone, implicating a requirement for gene expression in the response. Midcollicular decerebration (which removed the diencephalon) attenuated, whereas decortication (which spared the diencephalon) did not affect the respiratory response to progesterone. Thus, the diencephalon appears to be a critical neuroanatomical substrate for the response. These results indicate that the respiratory response to progesterone is mediated, at a hypothalamic site, via a genomic mechanism with characteristics consistent with the prototypic mechanism for progesterone actions.

The androgen-binding protein gene is expressed in male and female rat brain.

Extracellular androgen-binding proteins (ABP) are thought to modulate the regulatory functions of androgens and the trans-acting nuclear androgen receptor. Testicular ABP and plasma sex hormone-binding globulin (SHBG), which is produced in liver, are encoded by the same gene. We have now found that the ABP-SHBG gene is also expressed in male and female rat brain. Immunoreactive ABP was found to be present in neuronal cell bodies throughout the brain as well as in fibers of the hypothalamic median eminence. The highest concentrations of immunoreactive cell bodies were located in the supraoptic and paraventricular nuclei. Likewise, ABP mRNA was present in all brain regions examined. Analysis of cDNA clones representing brain ABP mRNAs revealed amino acid sequence differences in brain and testicular ABPs. The protein encoded by an alternatively processed RNA has sequence characteristics suggesting that the protein could act as a competitior of ABP binding to cell surface receptors. These data and gene-sequencing experiments indicate that a specific ABP gene promoter is used for transcription initiation in brain. ABP may function in brain as an androgen carrier protein; however, in view of the widespread presence of ABP and ABP mRNA in brain, the protein may have a much broader, yet unknown, function.

Activation of alpha 2-adrenoceptors causes inhibition of calcium channels but does not modulate inwardly-rectifying K+ channels in caudal raphe neurons.

Many neurotransmitter receptors that interact with pertussis toxin-sensitive G proteins, including the alpha 2-adrenergic receptor, can modulate both voltage-dependent calcium channels and G protein-coupled inwardly-rectifying K+ channels. Serotonergic neurons of the medulla oblongata (nucleus raphe obscurus and nucleus raphe pallidus), which provide a major projection to sympathetic and motor output systems, receive a catecholaminergic input and express alpha 2-adrenergic receptors. Therefore, we tested the effects of norepinephrine on voltage-dependent calcium channels and G protein-coupled inwardly-rectifying K+ channels in neonatal raphe neurons using whole-cell recording in a brainstem slice preparation. Calcium channel currents were inhibited by norepinephrine in the majority of raphe neurons tested (88%) and in all identified tryptophan hydroxylase-immunoreactive (i.e. serotonergic) neurons. When tested in the same neurons, the magnitude of calcium current inhibition by norepinephrine (approximately 25%) was less than that induced by 5-hydroxytryptamine (approximately 50%). The norepinephrine-induced calcium current inhibition was mediated by alpha 2-adrenergic receptors; it was mimicked by UK 14304, an alpha 2-adrenergic receptor agonist and blocked by idazoxan, an alpha 2-adrenergic receptor antagonist, but not affected by prazosin or propanolol (alpha 1 and beta adrenergic antagonists, respectively). Calcium current inhibition by norepinephrine was essentially eliminated following application of omega-Conotoxin GVIA and omega-Agatoxin IVA, indicating that norepinephrine modulated N- and P/Q-type calcium channels predominantly. Calcium current inhibition by norepinephrine was voltage-dependent and mediated by pertussis toxin-sensitive G proteins. Thus, as expected, alpha 2-adrenergic receptor activation inhibited N- and P/Q-type calcium currents in medullary raphe neurons via pertussis toxin-sensitive G proteins. In parallel experiments, however, we found that norepinephrine had no effect on G protein-coupled inwardly-rectifying K+ channels in any raphe neurons tested, despite the robust activation of those channels in the same neurons by 5-hydroxytryptamine. Together, these data indicate that alpha 2-adrenergic receptors can modulate N- and P/Q-type calcium channels in caudal medullary raphe neurons but do not couple to the G protein-coupled inwardly-rectifying K+ channels which are also present in those cells. This is in contrast to the effect of 5-hydroxytryptamine1A receptor activation in caudal raphe neurons, and indicates a degree of specificity in the signalling by different pertussis toxin-sensitive G protein-coupled receptors to voltage-dependent calcium channels and G protein-coupled inwardly-rectifying K+ channels even within the same cell system.

Postnatal changes in rat hypoglossal motoneuron membrane properties.

Intracellular recording techniques were used to characterize changes that take place in rat hypoglossal motoneuronal excitability from early postnatal stages to adulthood. This study focused primarily on the first two weeks of postnatal life, when major changes in the maturation of the neuromuscular system take place. Neonatal hypoglossal motoneurons were identified by their location within the hypoglossal nucleus and by their characteristic electrophysiology. These criteria were supported by antidromic activation and intracellular staining of retrogradely labeled hypoglossal motoneurons. Action potential duration decreased progressively during postnatal development. The reduction was primarily due to a more rapid repolarization, suggesting developmental changes in voltage-dependent potassium conductances. The duration of the calcium-dependent afterhyperpolarization decreased by half during the first two weeks of postnatal life. Changes in subthreshold responses included a decrease in input resistance and an increase in the degree of hyperpolarizing sag and inward rectification with age. Rheobase current was negatively correlated with input resistance, and increased progressively during postnatal development. Membrane time constant decreased almost four-fold over the first two postnatal weeks, suggesting that membrane resistivity is not constant. This decrease in membrane resistivity could account for a large fraction of the change in input resistance and rheobase with age. Thus, the early postnatal development of the rat includes systematic changes in the electrophysiological properties of motoneurons innervating tongue muscles. Some of these modifications are not easily explained by a mere change in neuronal surface area but likely involve changes in the density of expressed ion channels.

Depolarization and stimulation of neurons in nucleus tractus solitarii by carbon dioxide does not require chemical synaptic input.

The effects of elevated CO2 (i.e. hypercapnia) on neurons in the nucleus tractus solitarii were studied using extracellular (n = 82) and intracellular (n = 33) recording techniques in transverse brain slices prepared from rat. Synaptic connections from putative chemosensitive neurons in the ventrolateral medulla were removed by bisecting each transverse slice and discarding the ventral half. In addition, the response to hypercapnia in 20 neurons was studied during high magnesium-low calcium synaptic blockade. Sixty-five per cent of the neurons (n = 75) tested were either insensitive or inhibited by hypercapnia. However, 35% (n = 40) were depolarized and/or increased their firing rate during hypercapnia. Nine out of 10 CO2-excited neurons retained their chemosensitivity to CO2 in the presence of high magnesium-low calcium synaptic blockade medium. Our findings demonstrate that many neurons in the nucleus tractus solitarii were depolarized and/or increased their firing rate during hypercapnia. These neurons were not driven synaptically by putative chemosensitive neurons of the ventrolateral medulla since this region was removed from the slice. Furthermore, because chemosensitivity persisted in most neurons tested during synaptic blockade, we conclude that some neurons in the nucleus tractus solitarii are inherently CO2-chemosensitive. Although the function of dorsal medullary chemosensitive neurons cannot be determined in vitro, their location and their inherent chemosensitivity suggest a role in cardiorespiratory central chemoreception.

Thyrotropin-releasing hormone causes excitation of rat hypoglossal motoneurons in vitro.

A brainstem slice preparation and conventional intracellular recording techniques were used to study the effects of the neuropeptide thyrotropin-releasing hormone (TRH) on adult rat hypoglossal motoneurons (HMs) in vitro. We found that TRH (0.1-10 microM) had two effects: 1) it caused depolarization of HMs and 2) decreased their input conductance. We tested the effects of TRH on HMs using a sinusoidal current injection paradigm to approximate the rhythmic activity of HMs in vivo. Waves of injected current that elicited only subthreshold behavior in control conditions caused repetitive firing in the presence of TRH. Compensating for the TRH-induced depolarization by hyperpolarizing direct current injection revealed the consequences of decreased input conductance in isolation. Under these conditions, the spike-firing of HMs at the peak of the sinusoid was still enhanced. In addition, the maximal hyperpolarization at the nadir of the current wave was also increased. This suggests that in the presence of TRH, the effects of both excitatory and inhibitory synaptic inputs on HMs are enhanced and the contrast between excitation and inhibition is sharpened.

Regulation of gene expression by hypoxia.

The present study was undertaken to determine if gene expression for tyrosine hydroxylase (TH), the rate limiting enzyme in the biosynthesis of catecholamines, is regulated in the carotid body, sympathetic ganglia and adrenal medulla by hypoxia. We found that a reduction in oxygen tension from 21% to 10% caused a substantial increase (200% at 1 hour and 500% at 6 hours exposure) in the concentration of TH mRNA in carotid body type I cells but not in either the sympathetic ganglia or adrenal gland. In addition, we found that hypercapnia, another natural stimulus of carotid body activity, failed to enhance TH mRNA in type I cells. Removal of the sensory and sympathetic innervation of the carotid body failed to prevent the induction of TH mRNA by hypoxia in type I cells. Our results show that TH gene expression is regulated by hypoxia in the carotid body but not in other peripheral catecholamine synthesizing tissue and that the regulatory mechanism is intrinsic to type I cells.

Chronic estrogen exposure maintains elevated levels of progesterone receptor mRNA in guinea pig hypothalamus.

We performed in situ hybridization on hypothalamic sections from ovariectomized guinea pig using a cocktail of three 35S-labeled oligonucleotides complementary to mammalian progesterone receptor (PR) cDNA. PR mRNA was readily detected in hypothalamic neurons from guinea pigs pretreated with 17 beta-estradiol benzoate (E2B), but not from animals which did not receive supplemental E2B. The distribution of PR mRNA-containing cells corresponded well with previous localizations of PR in guinea pig. In contrast to earlier reports of E2B regulation of PR mRNA in rat hypothalamus, however, we found that PR mRNA remained elevated during chronic exposure to E2B (up to 10 days) in guinea pig.

Low-voltage-activated calcium channel subunit expression in a genetic model of absence epilepsy in the rat.

The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an inbred strain of rats that display many of the characteristics of human absence epilepsy. In these rats, reciprocal thalamocortical projections play a critical role in the generation of spike-and-wave discharges that characterize absence seizures. When compared to those of the non-epileptic control strain, juvenile animals of the GAERS strain reportedly possess higher-amplitude T-type calcium currents in neurons of the thalamic reticular nucleus (nRt). We hypothesized that differences in calcium currents seen between GAERS and controls result from differences in expression of genes for low-voltage-activated calcium channels. Quantitative in situ hybridization was used to compare expression of alpha1G, alpha1H, alpha1I, and alpha1E calcium channel subunit mRNAs from adult and juvenile animals of the two strains. We found higher levels of alpha1H mRNA expression in nRt neurons of juvenile animals (34.9+/-2. 3 vs. 28.4+/-1.8 grains/10(3) pixels, p<0.05), perhaps accounting in part for earlier reports of elevated T-type current amplitude in those cells. In adult GAERS animals, we found elevated levels of alpha1G mRNA in neurons of the ventral posterior thalamic relay nuclei (64.8+/-3.5 vs. 53.5+/-1.7 grains/10(3) pixels, p<0.05), as well as higher levels of alpha1H mRNA in nRt neurons (32.6+/-0.8 vs. 28.2+/-1.6 grains/10(3) pixels, p<0.05). These results suggest that the epileptic phenotype apparent in adult GAERS may result in part from these significant, albeit small ( approximately 15-25%), elevations in T-type calcium channel mRNA levels.

Complex structure and regulation of the ABP/SHBG gene.

Extracellular androgen-binding proteins (ABPs) are thought to modulate the regulatory functions of androgens and the trans-acting nuclear androgen receptor. Testicular ABP and plasma sex hormone-binding globulin (SHBG), which is produced in the liver, are encoded by the same gene. We report here that the ABP/SHBG gene is also expressed in fetal rat liver and adult brain. Immunoreactive ABP was localized in the brain and fetal liver and mRNAs were identified in both tissues by northern blot hybridization. Analysis of brain and fetal liver cDNA clones revealed alternatively processed RNAs with sequence characteristics suggesting the encoded proteins could act as competitors of ABP/SHBG binding to cell surface receptors. One cDNA represented a fused transcript of the ABP/SHBG gene and the histidine decarboxylase gene that was apparently formed by a trans-splicing process. Gene sequencing experiments indicate that tissue-specific ABP/SHBG gene promoter-enhancer elements are utilized in testis, brain and fetal liver. These data demonstrate that the structure, RNA transcript processing and likely regulation of the ABP/SHBG gene are very complex.

Central neural mechanisms of progesterone action: application to the respiratory system.

Around the turn of the century, it was recognized that women hyperventilate during the luteal phase of the menstrual cycle and during pregnancy. Although a causative role for the steroid hormone progesterone in this hyperventilation was suggested as early as the 1940s, there has been no clear indication as to the mechanism by which it produces its respiratory effects. In contrast, much mechanistic information has been obtained over the same period about a different effect of progesterone, i.e., the facilitation of reproductive behaviors. In this case, the bulk of the evidence supports the hypothesis that progesterone acts via a genomic mechanism with characteristics not unlike those predicted by classic models for steroid hormone action. We recently, therefore, undertook a series of experiments to test predictions of those same models with reference to the respiratory effects of progesterone. Here we highlight the results of those studies; as background to and precedent for our experiments, we briefly review previous work in which effects of progesterone on respiration and reproductive behaviors have been studied. Our results indicate that the respiratory response to progesterone is mediated at hypothalamic sites through an estrogen- (E2) dependent progesterone receptor- (PR) mediated mechanism requiring RNA and protein synthesis, i.e., gene expression. The E2 dependence of the respiratory response to progesterone is likely a consequence of the demonstrated induction of PR mRNA and PR in hypothalamic neurons by E2. In short, we found that neural mechanisms underlying the stimulation of respiration by progesterone were similar to those mediating its reproductive effects.

Development of hypoglossal motoneurons.

Hypoglossal motoneurons (HMs) are brain stem motoneurons that innervate tongue muscles. Their function is critical in the control of the upper airway. Results from in vitro studies of rat HMs have shown that properties of HMs change during the postnatal period. For example, these studies have uncovered changes in HM morphology and electrical properties (both in ion channels and firing properties) as well as changes in chemical synaptic transmission to HMs during the postnatal period. Morphologically, a marked reduction in complexity of the dendritic tree takes place over the first 2 wk postnatal. In terms of electrical properties, a substantial and progressive fall in motoneuronal input resistance occurs during the first month of life, due to a decrease in specific membrane resistivity. This is primarily responsible for the progressive increase in rheobase and consequent reduction in cell excitability. In addition, the densities of at least two types of membrane ion channels are altered in early postnatal life, contributing to changes in their electroresponsive properties. On the one hand, the depolarizing mixed cationic current that is activated by membrane hyperpolarization was found to be approximately 10-fold larger in adult than in neonatal HMs. By contrast, neonatal HMs possess a transient low-voltage-activated T-type Ca2+ channel with a low single-channel conductance (approximately 7 pS), the density of which rapidly declines during the early postnatal period. The functional relevance of these and other changes occurring during the postnatal period is discussed.

Effects of thyrotropin-releasing hormone on rat motoneurons are mediated by G proteins.

Numerous transmitter receptors are linked via GTP-binding proteins (G proteins) to membrane phosphoinositide metabolism by phospholipase C (PLC) and generation of second messengers such as activated protein kinase C (PKC), inositol trisphosphate (IP3) and/or elevations in intracellular calcium. In many cases, these same receptors also inhibit a resting ('leak') potassium current (IK(L)), thereby depolarizing neurons. It is unclear if activation of this PLC pathway mediates inhibition of IK(L) by neurotransmitter receptors. Therefore, we tested the contribution of this pathway to the TRH-induced inhibition of IK(L) in rat hypoglossal motoneurons (HMs) using conventional intracellular recording in brainstem slices. When HMs were recorded with electrodes containing 3 M KCl or 30 mM GTP (in KCl), TRH induced a depolarization that recovered quickly (within 8-10 min) and could be repeated with only modest tachyphylaxis (< 20%). However, with electrodes containing the non-hydrolyzable G protein activator, GTP gamma S (10 mM), the TRH-induced depolarization was long lasting (up to 1 h); with electrodes containing the G protein inhibitor, GDP beta S (20 mM) the tachyphylaxis with repeated TRH application was exaggerated (approximately 60%). Activation of PKC by phorbol dibutyrate (10 microM in perfusate) neither mimicked nor occluded the effects of TRH. There were no effects on membrane potential, input resistance (RN) or the response to TRH in HMs during long recordings with electrodes containing high concentrations of IP3 (60 mM).(ABSTRACT TRUNCATED AT 250 WORDS)