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Transfer of information about taste from the nucleus of the solitary tract to the parabrachial nucleus of the pons.

In the study of the neural code for gustation, the relative sensitivity of a cell to a variety of taste stimuli is defined as its response profile. To study the construction of response profiles from incoming signals, electrophysiological responses to NaCl, HCI, quinine-HCl, sucrose and Na saccharin were recorded simultaneously in pairs of single cells: one in the nucleus of the solitary tract (NTS) and the other in the parabrachial nucleus of the pons (PbN), respectively the first and second synapses in the central pathway for gustation. Of 37 units recorded in the NTS and 32 in the PbN, 12 (32%) pairs showed evidence of functional connectivity. Although PbN responses were significantly larger than those in the NTS in general, no amplification of NTS activity was apparent among those units that were functionally connected. Analysis of NTS-PbN connectivity patterns suggests that PbN units receive input from NTS units with response profiles that are both similar and different from their own pattern of sensitivities. Further analysis suggests that the stimulus-selectivity of the response profile of a PbN unit may be determined by stimulus-selective input from NTS cells that show similar response profiles. However, input from NTS cells with response profiles different from their own appears to be non-stimulus-selective. Analysis of the organization of response profiles in the two structures suggests that the cells in both the NTS and PbN cannot be easily distinguished by their patterns of sensitivity to taste stimuli.

Animals↗

Endogenous nitric oxide in the rat pons promotes sleep.

Pontine cholinergic structures are known to play a key role in the regulation of vigilance states associated with desynchronised EEG, i. e., wakefulness and paradoxical sleep. As the cholinergic cells of these nuclei, the pedunculopontine tegmentum (PPT) and the laterodorsal tegmentum, are enriched with nitric oxide synthase (NOS), we tested the hypothesis that nitric oxide (NO) in the pons is implicated in wake and sleep regulation. For this reason, a NOS inhibitor, a NO precursor and a NO donor were injected in the PPT of rats. Vigilance states were recorded for 6 h following the injections. Quantification of vigilance states after drug injections were compared to those obtained in control conditions. It appeared that the NO donor had a slight effect on vigilance states, but the NOS inhibitor decreased sleep and inversely the NO precursor increased sleep. These results show for the first time in the rat that a NOS inhibitor, injected directly into the PPT, is able to reduce sleep and that a NO precursor had the opposite effect. They suggest that endogenous NO production in the PPT has a somnogenic effect. The participation of endogenous NO in vigilance regulation is discussed in light of the role attributed to pontine cholinergic system in wakefulness and sleep.

Anilides↗

Expression of cholinergic markers in the pons of Flinders rats.

The Flinders sensitive line of rats (FSL rats) have an altered REM sleep pattern which includes a shorter REM sleep latency and an increased percentage of REM sleep [R.M. Benca, D.H. Overstreet, M.A. Gilliland, D. Russell, B.M. Bergmann, W.H. Obermeyer, Increased basal REM sleep but no difference in dark induction or light suppression of REM sleep in Flinders rats with cholinergic supersensitivity, Neuropsychopharmacology 15 (1996) 45-51; P.J. Shiromani, D.H. Overstreet, D. Levy, C.A. Goodrich, S.A. Campbell, J. C. Gillin, Increased REM sleep in rats selectively bred for cholinergic hyperactivity, Neuropsychopharmacology 1 (1988) 127-133]. Cholinergic mechanisms have been implicated in REM sleep generation [reviewed in P.J. Shiromani, J.C. Gillin, S.J. Henriksen, Acetylcholine and the regulation of REM sleep: basic mechanisms and clinical implication for affective illness and narcolepsy, Annu. Rev. Pharmacol. Toxicol. 27 (1987) 137-156]. In the present study, specific aspects of the cholinergic system were examined in the pontine region of the FSL rats. The number of cholinergic neurons in the LDT and PPT were not different in FSL and control rats. Analysis of steady state levels of mRNAs encoding the acetylcholine synthesizing protein, choline acetyltransferase (ChAT) or the m2, m3 and m5 muscarinic receptor subtypes were also comparable in FSL and control rats. These data raise the possibility that the cellular events underlying the altered REM sleep pattern in FSL rats may include mechanisms that effect the muscarinic or nicotinic receptor in the pons.

Acetylcholine↗

Noradrenaline transporter expression in the pons and medulla oblongata of the rat: localisation to noradrenergic and some C1 adrenergic neurones.

Catecholaminergic neurotransmission is normally terminated by rapid re-uptake of the neurotransmitter by a high-affinity Na+/Cl--dependent plasma membrane transporter. Specific transporters have been cloned for both dopamine (DAT) and noradrenaline (NAT) in the rat. While DAT has been studied extensively, NAT expression has received less attention, particularly at the protein level. We used an antibody generated against a 49 residue segment of an extracellular loop region of NAT to study expression of the transporter protein throughout the rat pons and medulla oblongata. NAT was expressed in over 95% of noradrenergic neurones in the A1, A2/area postrema, A5, A6/locus subcoeruleus, and A7 noradrenergic groups. Approximately 10% of C1 adrenergic neurones located in the rostral ventrolateral medulla (RVL) also expressed NAT. Expression of NAT mRNA in bulbospinal C1 cells was confirmed using single-cell reverse transcription polymerase chain reaction (RT-PCR) of acutely isolated RVL neurones. Spinally projecting neurones were identified by retrograde labelling with rhodamine beads, and C1 neurones were identified by RT-PCR using primers specific for tyrosine hydroxylase (TH) or phenylethanolamine N-methyltransferase (PNMT) mRNAs. Thirteen percent of adrenergic bulbospinal neurones tested expressed NAT mRNA. C1 neurones are potentially important in cardiovascular control and blood pressure regulation, and the identification of NAT expression in a sub-population of these neurones provides further evidence for the heterogeneity of this neuronal population.

Animals↗

Ultrastructural and permeability features of microvessels in the hippocampus, cerebellum and pons of senescence-accelerated mice (SAM).

We previously reported that the accumulation of blood-borne radiolabelled serum albumin in brain parenchyma increased with aging, especially in senescence-accelerated mice (SAMP8), which showed age-related deficits in learning and memory. In this study, in order to examine morphological events related to the age-related increase of the brain accumulation of serum albumin, the transvascular passage of blood-borne horseradish peroxidase (HRP) and ultrastructural features of microvessels were examined in the hippocampus, cerebellum and pons of SAMP8 and SAMR1 (control) mice. Ultrastructural examination of the hippocampus showed that the staining for HRP was occasionally spreading throughout the parajunctional cytoplasm of the endothelial cell of aged SAMP8 mice, but not in young SAMP8 mice nor in SAMR1 mice. The number of vessels showing the staining reaction for HRP in the parajunctional cytoplasm of the endothelial cells in aged SAMP8 mice increased significantly compared with that in the others. Electron microscopic morphometry showed that there were no significant differences among the number of HRP-positive vesicles per unit area of the endothelial cell cytoplasm in young and old mice of both strains. The staining reaction for HRP was not seen in the basal lamina of microvessels and the perivascular neuropil in all mice examined. Perivascular lipofuscin-like granules and collagen deposits, swelling of astroglial perivascular endfeet and perivascular cells containing foamy, lipid-like droplets were frequently found in several brain regions of aged SAMP8 mice. The perivascular cells with a few lipid-like droplets and more electron-homogeneous lysosomes were occasionally seen in SAMR1 and young SAMP8, while the other findings were scarcely observed in SAMR1 and young SAMP8 mice. These findings suggest that the blood-brain barrier to HRP was preserved in microvessels in three brain regions of SAM mice but the blood microvessels showed some age-related ultrastructural alterations in SAMP8 brains. Uncontrolled passage of HRP through the parajunctional cytoplasm of the endothelial cells may partly contribute to the age-related increase of accumulation of serum albumin in SAMP8 brains.

Aging↗

Tuberculoma of the pons.

A case of a pontine tuberculoma in a 12-year-old male from Somalia is presented. Cranial magnetic resonance imaging, performed in Abu Dhabi 1 month before admission in Germany revealed a tumorous lesion in the pons with surrounding edema; a presumptive diagnosis of a pontine glioma was made. Chest radiograph disclosed a pulmonary infiltrate with cavitation, as well as hilar and left mediastinal lymphadenopathy, suggestive of active tuberculosis. Tuberculostatic therapy led to an improvement of the patient's clinical status and a significant reduction in the size of the pontine tuberculoma. Intracranial tuberculomas rarely are seen in industrialized countries. They should, however, be considered as an important part of the differential diagnosis of intracranial space-occupying lesions. In most cases, as in this patient, conservative therapy provides good or excellent results.

Antitubercular Agents↗

A false lesion in the center of the pons on magnetic resonance images.

Three-hundred pediatric patients were evaluated for pontine signal abnormalities with special reference to small nodular, central pontine lesions. The ages of the patients ranged from 1 year to 17 years (mean = 7.3 years). There were 157 males and 143 females. The magnetic resonance (MR) imaging examinations were performed at 0.5 Tesla. There were 26 cases out of the 300 patients with pontine involvement due to a variety of clinically proved disorders. Except for these, we noted four patients with nodular, central pontine changes in the remaining 274 cases (four out of 274 = approximately 1.5%). These appeared as hyperintense foci on T2-weighted images, and hypointense on T1-weighted images. They were approximately 2-3 mm in diameter, and confined exactly to the middle of the pons. There was no clinical correspondence for these. The condition was attributed to an artefact created by a relatively deep interpedincular cistern leading to a volume-averaging effect.

Adolescent↗

Changes in neuron activity in the dorsolateral part of the pons during stimulation of areas of the brainstem inhibiting movement and muscle tone.

Changes in the activity of 44 neurons in the mesencephalic locomotor region and 38 neurons in the pontine inhibitory zone were recorded during stimulation of the gigantocellular reticular nucleus and the dorsal part of the oral reticular nucleus of the pons, which evokes inhibition of rigid tone in the hindlimbs of decerebrate rats. Decreases in muscle tone were always accompanied by decreases in the spike frequency of neurons in the mesencephalic locomotor region and increases in the activity of neurons in the pontine inhibitory zone. It is suggested that stimulation of the inhibitory parts of the brainstem simultaneously activates the reticulospinal inhibitory system, hyperpolarizing spinal alpha-motoneurons, and inhibits the neuron population of the mesencephalic locomotor region, which relates to the induction of locomotion and muscle tone.

Animals↗

Dynamics of neuron spike activity in the oral nucleus of the pons during the sleep-waking cycle in cats.

Chronic experiments on five cats were performed to study the spike activity of neurons in the oral nucleus of the pons during waking, slow-wave sleep, and paradoxical sleep. Groups of neurons with different dynamics of spike frequency were identified. Cells with rare discharges during waking and slow-wave sleep and maximum spike frequencies in the phasic stage of paradoxical sleep were regarded as PS-on neurons. Cells discharging at maximum frequency during waking, with decreases in frequency during slow-wave sleep and further decreases in paradoxical sleep, were regarded as PS-off neurons. Cells showing decreases in discharge frequency on the transition from waking to slow-wave sleep and increases in discharge frequency in paradoxical sleep, with grouped spikes during oculomotor activity, appeared to be responsible for generating the phasic phenomena of paradoxical sleep. The question of the involvement of neurons of different populations in the mechanisms of paradoxical sleep is discussed.

Action Potentials↗

Attack, eating, drinking, and gnawing elicited by electrical stimulation of rat mesencephalon and pons.

Eating, drinking, and gnawing were electrically elicited from the rat mesencephalon in the vicinity of the lateral branch of the descending medial forebrain bundle, but attack was evoked from the dorsomedial tegmentum adjacent to the central gray. The effective zones continued further caudally to the dorsal posterior pons. Unlike hypothalamically elicited behavior, eating, drinking, and gnawing often persisted 5-40 sec after termination of stimulation. Vocalization and escape activity were obtained principally from the vicinity of central pain pathways originating from the anterolateral cord. Other electrodes produced eating, drinking, gnawing, and grooming, which began only after termination of stimulation.

Aggression↗

Motivated behaviors elicited from hypothalamus, midbrain, and pons of the guinea pig (Cavia porcellus).

Eating, drinking, biting attack, male mating behavior, and gnawing were elicited by electrical stimulation through electrodes located predominantly in a region extending from the preoptic area through the lateral hypothalamus into the ventral midbrain. Escape and digging were elicited from a parallel but more medial region that overlapped the lateral zone only in the preoptic-anterior hypothalamic area. Several differentiable vocalizations were produced from sites distributed through most, although not all, areas explored. Sites yielding painlike responses were located principally in the vicinity of the presumed pain pathway traced after anterolateral cordotomy in other species. Reward was obtained from widespread sites that were generally congruent with catecholaminergic systems as described in the rat. Although there was considerable overlap of the effective zones for many responses, their underlying mechanisms were differentiated anatomically by localized differences in their distribution or functionally by the elicitation of pure responses from some electrodes. Response mechanisms localized in the brain stem of the guinea pig generally resembled those in the rat, although there were differences in details, especially in the posterior midbrain and pons.

Aggression↗

Allelic expression of serotonin transporter (SERT) mRNA in human pons: lack of correlation with the polymorphism SERTLPR.

An insertion/deletion polymorphism in the SERT linked promoter region (SERTLPR), previously reported to regulate mRNA expression in vitro, has been associated with mental disorders and response to psychotropic drugs. Contradictory evidence, however, has raised questions about the role of SERTLPR in regulating mRNA expression in vivo. We have used analysis of allelic expression imbalance (AEI) of SERT mRNA to assess quantitatively the contribution of SERTLPR to mRNA expression in human post-mortem pons tissue sections containing serotonergic neurons of the dorsal and median raphe nuclei. Any difference in the expression of one allele over the other indicates the presence of cis-acting elements that differentially affect transcription and/or mRNA processing and turnover. Using a marker SNP in the 3' untranslated region of SERT mRNA, statistically significant differences in allelic mRNA levels were detected in nine out of 29 samples heterozygous for the marker SNP. While the allelic expression differences were relatively small (15-25%), they could nevertheless be physiologically relevant. Although previous results had suggested that the long form of SERTLPR yields higher mRNA levels than the short form, we did not observe a correlation between SERTLPR and allelic expression ratios. Also in contrast to previous results, we found no correlation between SERTLPR and allelic expression ratios or SERT mRNA levels in B-lymphocytes. This study demonstrates that regulation of SERT mRNA is independent of SERTLPR, but could be associated with polymorphisms in partial linkage disequilibrium with SERTLPR.

3' Untranslated Regions↗

Auditory dysfunction following a gunshot wound of the pons.

A patient with a gunshot wound penetrating the right side of the brainstem at the level of the pons was given a test battery to evaluate peripheral hearing function and central auditory processing abilities. A month later, the left ear had a loss of sensitivity for high frequency tones, decreased speech discrimination, and excess tone decay. Two years later these deficits had resolved. However, a central auditory impairment remained, affecting the right ear score on Binaural Fusion and left ear scores on dichotic tasks and tonal pattern sequences.

Adolescent↗

The projections of the midbrain periaqueductal grey to the pons and medulla oblongata in rats.

It is now established that stimulation of the ventrolateral midbrain periaqueductal grey (PAG) evokes inhibition of nociceptive spinal neurons, which results in analgesia and a powerful attenuation of pain behaviour. It is postulated that the PAG exerts this inhibitory effect on spinal nociceptive functions through the activation of descending serotonergic and noradrenergic pathways that arise from the rostral ventromedial medulla (RVM) and pontine noradrenergic nuclei. To investigate the neuroanatomical substrate of this functional link between the PAG and RVM, as well as the pontine noradrenergic nuclei in the rat, we labelled axons that project from the ventrolateral PAG to various regions of the pons and medulla oblongata using the anterograde tracing substance, Phaseolus vulgaris leucoagglutinin. We demonstrated that some of PAG efferents really do terminate in the RVM and pontine noradrenergic nuclei, but a substantial proportion of them project to the intermediate subdivision of the pontobulbar reticular formation. Combining the axonal tracing with serotonin- and tyrosine-hydroxylase-immunohistochemistry, we also found that, in contrast to previous results, PAG efferents make relatively few appositions with serotonin- and tyrosine-hydroxylase-immunoreactive neurons in the RVM and pontine noradrenergic nuclei; most of them terminate in nonimmunoreactive territories. The results suggest that the ventrolateral PAG may activate a complex pontobulbar neuronal assembly including neurons in the intermediate subdivision of the pontobulbar reticular formation, serotonin- and tyrosine-hydroxylase-immunoreactive and nonimmunoreactive neurons in the RVM and pontine noradrenergic nuclei. This pontobulbar neural circuitry, then, may mediate the PAG-evoked activities towards the spinal dorsal horn resulting in the inhibition of spinal nociceptive functions.

Animals↗

Genetic inactivation of prohormone convertase (PC1) causes a reduction in cholecystokinin (CCK) levels in the hippocampus, amygdala, pons and medulla in mouse brain that correlates with the degree of colocalization of PC1 and CCK mRNA in these structures in rat brain.

Prohormone convertase (PC1) is found in endocrine cell lines that express cholecystokinin (CCK) mRNA and process pro CCK to biologically active products. Other studies have demonstrated that PC1 may be a one of the enzymes responsible for the endoproteolytic cleavages that occur in pro CCK during its biosynthesis and processing. Prohormone convertase 1 (PC1) has a distribution that is similar to cholecystokinin (CCK) in rat brain. A moderate to high percentage of CCK mRNA-positive neurons express PC1 mRNA. CCK levels were measured in PC1 knockout and control mice to assess the degree to which loss of PC1 changed CCK content. CCK levels were decreased 62% in hippocampus, 53% in amygdala and 57% in pons-medulla in PC1 knockout mice as compared to controls. These results are highly correlated with the colocalization of CCK and PC1. The majority of CCK mRNA-positive neurons in the pyramidal cell layer of the hippocampus express PC1 mRNA and greater than 50% of CCK mRNA-positive neurons in several nuclei of the amygdala also express PC1. These results demonstrate that PC1 is important for CCK processing. PC2 and PC5 are also widely colocalized with CCK. It may be that PC2, PC5 or another non-PC enzyme are able to substitute for PC1 and sustain production of some amidated CCK. Together these enzymes may represent a redundant system to insure the production of CCK.

Amygdala↗

[Magnetic resonance tomography of non-tumorous lesions of the pons].

The paper gives details of the diagnostic value of MRI in 20 cases of non-tumorous lesions of the pons. MR findings in haematoma (3), vascular malformations (2), infarctions (6), encephalitis (1), demyelinations (6) and atrophies (2) resulted in signal changes typical of the kind of disease. A pontine volume increase or decrease was proved comparing the data of the normal and affected brain stem. The topography of lesions was clearly documented by MRI. Subacute haematomas were better outlined than by CT, while acute infarctions, foci of demyelination and one case of ponsencephalitis were proved only by MRI. Small calcifications and vessels of an arteriovenous malformation, however, caused the same MR signal patterns.

Adult↗

Craniosynostosis, ataxia, trigeminal anaesthesia and parietal alopecia with pons-vermis fusion anomaly (atresia of the fourth ventricle). Report of two cases.

A probably new syndrome of craniosynostosis, ataxia, trigeminal anaesthesia, and parietal alopecia area associated with pons-vermis fusion anomaly (atresia of the fourth ventricle), in two unrelated Mexican girls, is described. The cerebellar anomaly was proven by CT scan only and it correlated with ataxia. Other abnormalities seen in both patients were midfacial hypoplasia, bilateral corneal opacities, low-set ears, mental retardation and short stature. This disorder could be a new neurocutaneous syndrome.

Alopecia↗

Evidence for a possible glycinergic inhibitory neurotransmission in the midbrain and rostral pons of the rat studied by gephyrin.

The data on the glycinergic transmission in the rostral brainstem are both few and controversial. The present report provides evidence for a possible glycinergic transmission in Sprague-Dawley rats, based on observations of immunocytochemical labeling for gephyrin, a 93 kDa protein and a component of the functional glycine receptor. A monoclonal antibody against gephyrin was used, and the reaction product was visualized by means of avidin-biotin-peroxidase procedure. The reaction product in midbrain and rostral pons was found in neuronal perikarya and in proximal dendrites but in some cases the most distal dendritic branches were also labeled. The neuropil usually displayed a moderate staining with finely granulated reaction product. The most significant immunocytochemical signal was mainly encountered in large and medium-sized neuronal populations of the motor cranial nerve nuclei (III, IV, V), in the reticular formation (laterodorsal tegmental nucleus, pedunculopontine tegmental nucleus, deep mesencephalic nucleus), in the red nucleus, in the intermediate and deep gray strata of the superior colliculus. Only in the substantia nigra and the inferior colliculus the parvocellular cell populations were mainly labeled. The present data suggest a significant inhibitory glycinergic neurotransmission in the rostral brainstem, probably mediated by interneurons.

Animals↗