mu(1)- and 5-HT1-dependent mechanisms in the anterior pretectal nucleus mediate the antinociceptive effects of retrosplenial cortex stimulation in rats

Aim: This study examines if injection of cobalt chloride (CoCl2) or antagonists of muscarinic cholinergic (atropine), mu(1)-opioid (naloxonazine) or 5-HT1 serotonergic (methiothepin) receptors into the dorsal or ventral portions of the anterior pretectal nucleus (APtN) alters the antinociceptive effects of stimulating the retrosplenial cortex (RSC) in rats. Main method: Changes in the nociceptive threshold were evaluated using the tail flick or incision pain tests in rats that were electrically stimulated at the RSC after the injection of saline, CoCl2 (1 mM, 0.10 mu L) or antagonists into the dorsal or ventral APtN. Key findings: The injection of CoCl2, naloxonazine (5 mu g/0.10 mu L) or methiothepin (3 mu g/0.10 mu L) into the dorsal APtN reduced the stimulation-produced antinociception from the RSC in the rat tail flick test. Reduction of incision pain was observed following stimulation of the RSC after the injection of the same substances into the ventral APtN. The injection of atropine (10 ng/0.10 mu L) or ketanserine (5 mu g/0.10 mu L) into the dorsal or ventral APtN was ineffective against the antinociception resulting from RSC stimulation. Significance: mu(1)-opioid- and 5-HT1-expressing neurons and cell processes in dorsal and ventral APtN are both implicated in the mediation of stimulation-produced antinociception from the RSC in the rat tail flick and incision pain tests, respectively. (c) 2012 Elsevier Inc. All rights reserved.

Antinociceptive effect of stimulating the zona incerta with glutamate in rats

The zona incerta (ZI) is a subthalamic nucleus connected to several structures, some of them known to be involved with antinociception. The 21 itself may be involved with both antinociception and nociception. The antinociceptive effects of stimulating the ZI with glutamate using the rat tail-flick test and a rat model of incision pain were examined. The effects of intraperitoneal antagonists of acetylcholine, noradrenaline, serotonin, dopamine, or opioids on glutamate-induced antinociception from the ZI in the tail-flick test were also evaluated. The injection of glutamate (7 mu g/0.25 mu l) into the ZI increased tail-flick latency and inhibited post-incision pain, but did not change the animal performance in a Rota-rod test. The injection of glutamate into sites near the ZI was non effective. The glutamate-induced antinociception from the ZI did not occur in animals with bilateral lesion of the dorsolateral funiculus, or in rats treated intraperitoneally with naloxone (1 and 2 m/kg), methysergide (1 and 2 m/kg) or phenoxybenzamine (2 m/kg), but remained unchanged in rats treated with atropine, mecamylamine, or haloperidol (all given at doses of 1 and 2 m/kg). We conclude that the antinociceptive effect evoked from the ZI is not due to a reduced motor performance, is likely to result from the activation of a pain-inhibitory mechanism that descends to the spinal cord via the dorsolateral funiculus, and involves at least opioid, serotonergic and a-adrenergic mechanisms. This profile resembles the reported effects of these antagonists on the antinociception caused by stimulating the periaqueductal gray or the pedunculopontine tegmental nucleus. (C) 2012 Elsevier Inc. All rights reserved.

Ventral premammillary nucleus as a critical sensory relay to the maternal aggression network

Maternal aggression is under the control of a wide variety of factors that prime the females for aggression or trigger the aggressive event. Maternal attacks are triggered by the perception of sensory cues from the intruder, and here we have identified a site in the hypothalamus of lactating rats that is highly responsive to the male intruder—the ventral premammillary nucleus (PMv). The PMv is heavily targeted by the medial amygdalar nucleus, and we used lesion and immediate-early gene studies to test our working hypothesis that the PMv signals the presence of a male intruder and transfers this information to the network organizing maternal aggression. PMv-lesioned dams exhibit significantly reduced maternal aggression, without affecting maternal care. The Fos analysis revealed that PMv influences the activation of hypothalamic and septal sites shown to be mobilized during maternal aggression, including the medial preoptic nucleus (likely to represent an important locus to integrate priming stimuli critical for maternal aggression), the caudal two-thirds of the hypothalamic attack area (comprising the ventrolateral part of the ventromedial hypothalamic nucleus and the adjacent tuberal region of the lateral hypothalamic area, critical for the expression of maternal aggression), and the ventral part of the anterior bed nuclei of the stria terminalis (presently discussed as being involved in controlling neuroendocrine and autonomic responses accompanying maternal aggression). These findings reveal an important role for the PMv in detecting the male intruder and how this nucleus modulates the network controlling maternal aggression.

Cardiovascular effects of the microinjection of L-proline into the third ventricle or the paraventricular nucleus of the hypothalamus in unanesthetized rats

We investigated the cardiovascular effects of the microinjection of L-proline (L-Pro) into the third ventricle (3V) and its peripheral mechanisms. Different doses of L-Pro into the 3V caused dose-related pressor and bradycardiac responses. The pressor response to L-Pro injected into the 3V was potentiated by intravenous pretreatment with the ganglion blocker pentolinium (5 mg/kg), thus excluding any significant involvement of the sympathetic nervous system. Because the response to the microinjection of L-Pro into the 3V was blocked by intravenous pretreatment with the V1-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP (50 mu g/kg), it is suggested that these cardiovascular responses are mediated by a vasopressin release. The pressor response to the microinjection of L-Pro into the 3V was found to be mediated by circulating vasopressin, so, given that the paraventricular nucleus of the hypothalamus (PVN) is readily accessible from the 3V, we investigated whether the PVN could be a site of action for the L-Pro microinjected in the 3V. The microinjection of L-Pro (0.033 mu moles/0.1 mu l) into the PVN caused cardiovascular responses similar to those of injection of the 3V and were also shown to be mediated by vasopressin release. In conclusion, these results show that the microinjection of L-Pro into the 3V causes pressor and bradycardiac responses that could involve stimulation of the magnocellular cells of the PVN and release of vasopressin into the systemic circulation. Also, because the microinjection of L-Pro into the PVN caused a pressor response, this is the first evidence of cardiovascular effects caused by its injection in a supramedullary structure. (c) 2012 Wiley Periodicals, Inc.

Moxonidine into the lateral parabrachial nucleus reduces renal and hormonal responses to cell dehydration

The deactivation of the inhibitory mechanisms with injections of moxonidine (alpha(2)-adrenoceptor/imidazoline receptor agonist) into the lateral parabrachial nucleus (LPBN) increases hypertonic NaCl intake by intra- or extracellular dehydrated rats. In the present study, we investigated the changes in the urinary sodium and volume, sodium balance, and plasma vasopressin and oxytocin in rats treated with intragastric (i.g.) 2 M NaCl load (2 ml/rat) combined with injections of moxonidine into the LPBN. Male Holtzman rats (n=5-12/group) with stainless steel cannulas implanted bilaterally into LPBN were used. Bilateral injections of moxonidine (0.5 nmol/0.2 mu l) into the LPBN decreased i.g. 2 M NaCIinduced diuresis (4.6 +/- 0.7 vs. vehicle: 7.4 +/- 0.6 ml/120 min) and natriuresis (1.65 +/- 0.29 vs. vehicle: 2.53 +/- 0.17 mEq/120 min), whereas the previous injection of the alpha(2)-adrenoceptor antagonist RX 821002 (10 nmol/0.2 mu l) into the LPBN abolished the effects of moxonidline. Moxonidine injected into the LPBN reduced i.g. 2 M NaCl-induced increase in plasma oxytocin and vasopressin (14.6 +/- 2.8 and 2.2 +/- 0.3 vs. vehicle: 25.7 +/- 7 and 4.3 +/- 0.7 pg/ml, respectively). Moxonidine injected into the LPBN combined with i.g. 2 M NaCl also increased 0.3 M NaCl intake (7.5 +/- 1.7 vs. vehicle: 0.5 +/- 0.2 mEq/2 h) and produced positive sodium balance (2.3 +/- 1.4 vs. vehicle: -1.2 +/- 0.4 mEq/2 h) in rats that had access to water and NaCl. The present results show that LPBN alpha(2)-adrenoceptor activation reduces renal and hormonal responses to intracellular dehydration and increases sodium and water intake, which facilitates sodium retention and body fluid volume expansion. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Medial amygdaloid nucleus 5-HT2C receptors are involved in the hypophagic effect caused by zimelidine in rats

The medial amygdaloid nucleus (MeA) is a sub-region of the amygdaloid complex that has been described as participating in food intake regulation. Serotonin has been known to play an important role in appetite and food intake regulation. Moreover, serotonin 5-HT2C and 5-HT1A receptors appear to be critical in food intake regulation. We investigated the role of the serotoninergic system in the MeA on feeding behavior regulation in rats. The current study examined the effects on feeding behavior regulation of the serotonin reuptake inhibitor, zimelidine, administered directly into the MeA or given systemically, and the serotoninergic receptors mediating its effect. Our results showed that microinjection of zimelidine (0.2, 2 and 20 nmol/100 nL) into the MeA evoked dose dependent hypophagic effects in fasted rats. The selective 5-HT1A receptor antagonist WAY-100635 (18.5 nmol/100 nL) or the 5-HT1B receptor antagonist SB-216641 microinjected bilaterally into the MeA did not change the hypophagic effect evoked by local MeA zimelidine treatment. However, microinjection of the selective 5-HT2C receptor antagonist SB-242084 (10 nmol/100 nL) was able to block the hypophagic effect of zimelidine. Moreover, microinjection of the 5-HT2C receptor antagonist SB-242084 into the MeA also blocked the hypophagic effect caused by zimelidine administered systemically. These results suggest that MeA 5-HT2C receptors modulate the hypophagic effect caused by local MeA administration as well as by systemic zimelidine administration. Furthermore, 5-HT2C into the MeA could be a potential target for systemic administration of zimelidine. (C) 2012 Elsevier Ltd. All rights reserved.

The Dorsolateral Periaqueductal Gray and Its Role in Mediating Fear Learning to Life Threatening Events

The dorsolateral column of the periaqueductal gray (dlPAG) integrates aversive emotional experiences and represents an important site responding to life threatening situations, such as hypoxia, cardiac pain and predator threats. Previous studies have shown that the dorsal PAG also supports fear learning; and we have currently explored how the dlPAG influences associative learning. We have first shown that N-methyl-D-aspartate (NMDA) 100 pmol injection in the dlPAG works as a valuable unconditioned stimulus (US) for the acquisition of olfactory fear conditioning (OFC) using amyl acetate odor as conditioned stimulus (CS). Next, we revisited the ascending projections of the dlPAG to the thalamus and hypothalamus to reveal potential paths that could mediate associative learning during OFC. Accordingly, the most important ascending target of the dlPAG is the hypothalamic defensive circuit, and we were able to show that pharmacological inactivation using beta-adrenoceptor blockade of the dorsal premammillary nucleus, the main exit way for the hypothalamic defensive circuit to thalamo-cortical circuits involved in fear learning, impaired the acquisition of the OFC promoted by NMDA stimulation of the dlPAG. Moreover, our tracing study revealed multiple parallel paths from the dlPAG to several thalamic targets linked to cortical-hippocampal-amygdalar circuits involved in fear learning. Overall, the results point to a major role of the dlPAG in the mediation of aversive associative learning via ascending projections to the medial hypothalamic defensive circuit, and perhaps, to other thalamic targets, as well. These results provide interesting perspectives to understand how life threatening events impact on fear learning, and should be useful to understand pathological fear memory encoding in anxiety disorders.

Shape isomerism and shape coexistence effects on the Coulomb energy differences in the N = Z nucleus As-66 and neighboring T=1 multiplets

Excited states of the N = Z = 33 nucleus As-66 have been populated in a fusion-evaporation reaction and studied using gamma-ray spectroscopic techniques. Special emphasis was put into the search for candidates for the T = 1 states. A new 3(+) isomer has been observed with a lifetime of 1.1(3) ns. This is believed to be the predicted oblate shape isomer. The excited levels are discussed in terms of the shell model and of the complex excited Vampir approaches. Coulomb energy differences are determined from the comparison of the T = 1 states with their analog partners. The unusual behavior of the Coulomb energy differences in the A = 70 mass region is explained through different shape components (oblate and prolate) within the members of the same isospin multiplets. This breaking of the isospin symmetry is attributed to the correlations induced by the Coulomb interaction.

Treatment effects of bonded spurs associated with high-pull chincup therapy in the treatment of patients with anterior open bite

Introduction: The aim of this prospective clinical study was to investigate the cephalometric changes produced by bonded spurs associated with high-pull chincup therapy in children with Angle Class I malocclusion and anterior open bite. Methods: Thirty patients with an initial mean age of 8.14 years and a mean anterior open bite of -3.93 mm were treated with bonded spurs associated with chincup therapy for 12 months. An untreated control group of 30 subjects with an initial mean age of 8.36 years and a mean anterior open bite of -3.93 mm and the same malocclusion was followed for 12 months for comparison. Student t tests were used for intergroup comparisons. Results: The treated group demonstrated a significantly greater decrease of the gonial angle, and increase in overbite, palatal tipping of the maxillary incisors, and vertical dentoalveolar development of the maxillary and mandibular incisors compared with the control group. Conclusions: The association of bonded spurs with high-pull chincup therapy was efficient for the correction of the open bite in 86.7% of the patients, with a 5.23-mm (SD, +/- 1.69) overbite increase. (Am J Orthod Dentofacial Orthop 2012;142:487-93)

Diverse levels of an inwardly rectifying potassium conductance generate heterogeneous neuronal behavior in a population of dorsal cochlear nucleus pyramidal neurons

Leao RM, Li S, Doiron B, Tzounopoulos T. Diverse levels of an inwardly rectifying potassium conductance generate heterogeneous neuronal behavior in a population of dorsal cochlear nucleus pyramidal neurons. J Neurophysiol 107: 3008-3019, 2012. First published February 29, 2012; doi:10.1152/jn.00660.2011.-Homeostatic mechanisms maintain homogeneous neuronal behavior among neurons that exhibit substantial variability in the expression levels of their ionic conductances. In contrast, the mechanisms, which generate heterogeneous neuronal behavior across a neuronal population, remain poorly understood. We addressed this problem in the dorsal cochlear nucleus, where principal neurons exist in two qualitatively distinct states: spontaneously active or not spontaneously active. Our studies reveal that distinct activity states are generated by the differential levels of a Ba2+-sensitive, inwardly rectifying potassium conductance (K-ir). Variability in K-ir maximal conductance causes variations in the resting membrane potential (RMP). Low K-ir conductance depolarizes RMP to voltages above the threshold for activating subthreshold-persistent sodium channels (Na-p). Once Na-p channels are activated, the RMP becomes unstable, and spontaneous firing is triggered. Our results provide a biophysical mechanism for generating neural heterogeneity, which may play a role in the encoding of sensory information.

Searching for resonances in the unbound Be-6 nucleus by using a radioactive Be-7 beam

Knowledge of the He-3(He-3,2p)He-4 reaction is important for understanding stellar burning and solar neutrino production. Previous measurements have found a surprisingly large rise in the cross section at low energies that could be due to a low-energy resonance in the He-3 + He-3 (Be-6) system or electron screening. In the Be-6 nucleus, however, no excited states have been observed above the first 2(+) state at E (x) = 1.67 MeV up to 23 MeV, even though several are expected. The H-2(Be-7,H-3)Be-6 reaction has been studied for the first time to search for resonances in the Be-6 nucleus that may affect our understanding of the He-3(He-3,2p)He-4 reaction. A 100-MeV radioactive Be-7 beam from the Holifield Radioactive Ion Beam Facility (HRIBF) was used to bombard CD2 targets, and tritons were detected by using the silicon detector array (SIDAR). A combination of reaction mechanisms appears to be necessary to explain the observed triton energy spectrum.

beta-ADRENOCEPTORS IN THE MEDIAL AMYGDALOID NUCLEUS MODULATE THE TACHYCARDIAC RESPONSE TO RESTRAINT STRESS IN RATS

In the present study, we investigated the involvement of beta-adrenoceptors in the medial amygdaloid nucleus (MeA) in cardiovascular responses evoked in rats submitted to an acute restraint stress. We first pretreated Wistar rats with the nonselective beta-adrenoceptor antagonist propranolol microinjected bilaterally into the MeA (10, 15, and 20 nmol/100 nL) 10 min before exposure to acute restraint. The pretreatment with propranolol did not affect the blood pressure (BP) increase evoked by restraint. However, it increased the tachycardiac response caused by acute restraint when animals were pretreated with a dose of 15 nmol, without a significant effect on the BP response. This result indicates that beta-adrenoceptors in the MeA have an inhibitory influence on restraint-evoked heart rate (HR) changes. Pretreatment with the selective beta(2)-adrenoceptor antagonist ICI 118,551 (10, 15, and 20 nmol/100 nL) significantly increased the restraint-evoked tachycardiac response after doses of 15 and 20 nmol, an effect that was similar to that observed after the pretreatment with propranolol at a dose of 15 nmol, without a significant effect on the BP response. Pretreatment of the MeA with the selective beta(1)-adrenoceptor antagonist CGP 20712 (10, 15, and 20 nmol/100 nL) caused an opposite effect on the HR response, and a significant decrease in the restraint-evoked tachycardia was observed only after the dose of 20 nmol, without a significant effect on the BP response. Because propranolol is an equipotent antagonist of both beta(1) and beta(2)-adrenoceptors, and opposite effects were observed after the treatment with the higher doses of the selective antagonists ICI 118,551 and CGP 20712, the narrow window in the dose-response to propranolol could be explained by a functional antagonism resulting from the simultaneous inhibition of beta(1) and beta(2)-adrenoceptors by the treatment with propranolol. The present results suggest that beta(2)-adrenoceptors have an inhibitory influence on the restraint-evoked tachycardiac response, whereas beta(1)-adrenoceptors have a facilitatory influence on the restraint-evoked tachycardiac response. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Correlation Between Trochlear Groove Depth and Patellar Position During Open and Closed Kinetic Chain Exercises in Subjects With Anterior Knee Pain

The purpose of this study was to correlate the trochlear shape and patellar tilt angle and lateral patellar displacement at rest and maximal voluntary isometric contraction (MVIC) exercises during open (OKC) and closed kinetic chain (CKC) in subjects with and without anterior knee pain. Subjects were all women, 20 who were clinically healthy and 19 diagnosed with anterior knee pain. All subjects were evaluated and subjected to magnetic resonance exams during OKC and CKC exercise with the knee placed at 15, 30, and 45 degrees of flexion. The parameters evaluated were sulcus angle, patellar tilt angle and patellar displacement using bisect offset. Pearson's r coefficient was used, with p < .05. Our results revealed in knee pain group during CKC and OKC at 15 degrees that the increase in the sulcus angle is associated with a tilt increase and patellar lateral displacement. Comparing sulcus angle, patellar tilt angle and bisect offset values between MVIC in OKC and CKC in the knee pain group, it was observed that patellar tilt angle increased in OKC only with the knee flexed at 30 degrees. Based on our results, we conclude that reduced trochlear depth is correlated with increased lateral patellar tilt and displacement during OKC and CKC at 15 degrees of flexion in people with anterior knee pain. By contrast, 30 degrees of knee flexion in CKC is more recommended in rehabilitation protocols because the patella was more stable than in other positions.

PARAVENTRICULAR AND SUPRAOPTIC NUCLEI OF THE HYPOTHALAMUS MEDIATE CARDIOVASCULAR RESPONSES EVOKED BY THE MICROINJECTION OF NORADRENALINE INTO THE MEDIAL AMYGDALOID NUCLEUS OF THE RAT BRAIN

The medial amygdaloid nucleus (MeA) is a part of the limbic system and is involved in cardiovascular modulation. We previously reported that microinjection of noradrenaline (NA) into the MeA of unanesthetized rats caused pressor and bradycardiac responses, which were mediated by acute vasopressin release into the systemic circulation. In the present study, we tested the possible involvement of magnocellular neurons of the paraventricular (PVN) and/or supraoptic (SON) of the hypothalamus that synthesize vasopressin in the cardiovascular pathway activated by the microinjection of NA into the MeA. Pressor and bradycardiac responses to the microinjection of NA (27 nmol/100 nL) into the MeA were blocked by pretreatment of either the PVN or the SON with cobalt chloride (CoCl2, 1 mM/100 nL), thus indicating that both hypothalamic nuclei mediate the cardiovascular responses evoked by microinjection of NA Into the MeA. Our results suggest that the pressor and bradycardiac response caused by the microinjection of NA into the MeA is mediated by magnocellular neurons in both the PVN and SON. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Frontal-orbital advancement for the management of anterior plagiocephaly

The main purposes of this manuscript are to provide an overview of various modalities of surgical correction of anterior plagiocephaly and to emphasize their differences with the classic open frontal-orbital advancement. Advancement of technology provides development of many other ways to achieve the same results. The authors describe the classic open frontal-orbital advancement and compare with other proposed techniques for correction of frontal plagiocephaly. The main limitation of the use of new forms of treatment of the anterior plagiocephaly is the age of the patient. There is still no consensus on criteria for quantitative evaluation of surgical results, and new forms of treatment do not present results with long follow-up. Frontal-orbital advancement is the preferred procedure to correct unicoronal synostosis due to its universal indication regardless of the age and degree of deformation of the anterior plagiocephaly.