Visual cells in the pons of the brain.
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The pedunculopontine tegmental nucleus appears to influence striatal dopamine activity via cholinergic and glutamatergic afferents to dopaminergic cells of the substantia nigra pars compacta. We measured changes in striatal dopamine oxidation current (dopamine efflux) in response to electrical stimulation of the pedunculopontine tegmental nucleus using in vivo electrochemistry in urethane-anaesthetized rats. Pedunculopontine tegmental nucleus stimulation evoked a three-component change in striatal dopamine efflux, consisting of: (i) an initial rapid increase of 2 min duration; followed by (ii) a decrease below prestimulation levels of 9 min duration; then by (iii) a prolonged increase lasting 35 min. Intra-nigral infusions of the ionotropic glutamate receptor antagonist kynurenate (10 microg/ microL) or the nicotinic cholinergic receptor antagonist mecamylamine (5 microg/0.5 microL) selectively attenuated the rapid first component, while systemic injections of the muscarinic cholinergic antagonist scopolamine (5 mg/kg, i.p.) diminished the second and third components. In addition, intra-pedunculopontine tegmental nucleus infusions of the M2 muscarinic antagonist methoctramine (50 microg/ microL) selectively abolished the inhibitory second component, while intranigral infusions of scopolamine (200 microg/ microL) selectively abolished the prolonged third component. Intra-nigral infusions of the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine (2 microg/ microL) had no effect on pedunculopontine tegmental nucleus-elicited striatal dopamine efflux. These results suggest that the pedunculopontine tegmental nucleus utilizes nicotinic and ionotropic glutamate receptors in the substantia nigra to mediate rapid activation, M2-like muscarinic autoreceptors in the pedunculopontine tegmental nucleus to mediate decreased activation, and muscarinic receptors in the substantia nigra (probably of the M5 subtype) to mediate prolonged activation, of the nigrostriatal dopaminergic system.
The effects of the arousal-promoting peptide hypocretin on brain stem G protein activation and ACh release were examined using 16 adult Sprague-Dawley rats. In vitro[35S]GTPgammaS autoradiography was used to test the hypothesis that hypocretin-1-stimulated G protein activation is concentration-dependent and blocked by the hypocretin receptor antagonist SB-334867. Activated G proteins were quantified in dorsal raphe nucleus (DR), locus coeruleus (LC) and pontine reticular nucleus oral part (PnO) and caudal part (PnC). Concentration-response data revealed a significant (P < 0.001) effect of hypocretin-1 (2-2000 nm) in all brain regions examined. Maximal increases over control levels of [35S]GTPgammaS binding were 37% (DR), 58% (LC), 52% (PnO) and 44% (PnC). SB-334867 (2 micro m) significantly (P < 0.002) blocked hypocretin-1 (200 nm)-stimulated [35S]GTPgammaS binding in all four nuclei. This is the first autoradiographic demonstration that hypocretin-1 activates G proteins in arousal-related brain stem nuclei as a result of specific receptor interactions. This finding suggests that some hypocretin receptors in brain stem couple to inhibitory G proteins. In vivo microdialysis was used to test the hypothesis that PnO administration of hypocretin-1 increases ACh release in PnO. Dialysis delivery of hypocretin-1 (100 micro m) significantly (P < 0.002) increased (87%) ACh release. This finding is consistent with the interpretation that one mechanism by which hypocretin promotes arousal is by enhancing cholinergic neurotransmission in the pontine reticular formation.
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Endothelin-1 (ET-1), a potent vasoconstrictor, is widely distributed in the central nervous system. This article demonstrates the spatio-temporal expression of mouse preproendothelin-1 (mPPET-1) gene in pre- and perinatal mouse brain by in situ hybridization using a probe specific for mPPET-1. mPPET-1 mRNA expression was first observed in medulla at embryonic age 11.5 (E11.5) and the level became increasingly stronger toward later stages of development. At E18.5 and postnatal day 0.5 (D0.5), mPPET-1 mRNA was found in discrete nucleus group in ventrolateral medulla. mPPET-1 mRNA was also detected in thalamic reticular nucleus at E16.5, E18.5, and D0.5. These results showed that mPPET-1 mRNA is present in neurons of central cardiorespiratory region and drastically increased during the transition from episodic fetal breathing to continuous postnatal respiration (E18.5 to D0.5), implicating the important role of ET-1 in central cardiorespiratory control regulating the onset of respiration during this critical period.
Intracerebral Langerhans' cell histiocytosis (LCH) is rare and tends to involve the hypothalamus. The authors report a rare case of LCH in the temporal lobe that subsequently was followed by a brainstem lesion. This appears to be the first case of temporal lobe and brainstem LCH that has been treated successfully and published. A 24-year-old man complained of cacosmia and nausea with a slight headache. He had a left temporal LCH, which was removed completely, but developed a brainstem lesion a year later. The pontine LCH was treated with radiosurgery. The follow-up period was 4 years without any neurological or radiological symptoms or signs. The 12 cases of solitary intracranial non-hypothalamic LCH reported previously are reviewed. Gamma knife radiosurgery effectively controlled the local growth of the pontine LCH without adverse effect.
A patient with advanced AIDS presented with right conjugate gaze palsy and impaired adduction on left gaze (the one-and-a-half syndrome). The responsible pontine lesion involved the ipsilateral abducens nucleus and the adjacent medial longitudinal fasiculus (MLF), as demonstrated by magnetic resonance imaging (MRI). Tuberculosis (TB) was the etiology of the brainstem lesion. The patient had complete recovery after anti-tuberculosis treatment. The nuclear location of the tuberculoma is unusual and the reversal of this neuro-ophthalmologic syndrome is noteworthy.
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Using microiontophoresis on unanesthetized head-restrained cats, we have found two distinct groups of neurones exhibiting tonic discharge specific to paradoxical sleep (PS) (PS-on neurones) in the mesopontine tegmentum, which contains both cholinergic and non-cholinergic neurones. One group is characterized by a broad action potential, slow conduction velocity and an inhibitory response to a potent cholinergic agonist, carbachol, applied iontophoretically during PS. The other is characterized by a short action potential, fast conduction velocity and an excitatory response to applied carbachol. All PS-on neurones were excited by glutamate. The present findings demonstrate the existence of two types of PS-on neurones and suggest their cholinergic and noncholinergic neurochemical properties.
PURPOSE: The maintenance of long lasting bladder overactivity caused by cerebral infarction is believed to require transcription in the pontine micturition center. Therefore, we examined the influence of the RNA synthesis inhibitor actinomycin D (Banyu Pharmaceutical Co., Ltd., Tokyo, Japan) on bladder overactivity induced by left middle cerebral artery occlusion. MATERIALS AND METHODS: Rats under halothane anesthesia were injected with actinomycin D or vehicle (mannitol) into the bilateral dorsal pontine tegmentum, followed by middle cerebral artery occlusion. Awake rats were cystometrically examined for 12 hours. The expression of c-fos and zif268 mRNA in the dorsal pontine tegmentum was monitored with real-time polymerase chain reaction. RESULTS: Injection of actinomycin D produced a significant decrease in bladder capacity in sham operated rats but bladder capacity returned to control levels before sham operation within 6 hours. In cerebral infarcted rats pretreated with vehicle bladder capacity was significantly decreased after middle cerebral artery occlusion and it remained consistently below half of pre-occlusion capacity. Actinomycin D blocked the decrease in bladder capacity in cerebral infarcted rats. In actinomycin D treated cerebral infarcted rats bladder capacity gradually recovered and returned to the control level before middle cerebral artery occlusion within 10 hours. Actinomycin D suppressed an increase in c-fos mRNA expression 1 hour after middle cerebral artery occlusion as well as in zif268 3 hours after occlusion. Administering actinomycin D 0.5 or 1 hour after middle cerebral artery occlusion also suppressed bladder overactivity until at least 10 hours after occlusion but injection 3 hours after occlusion did not. CONCLUSIONS: These results indicate that an RNA synthesis inhibitor can prevent a late stage of bladder overactivity. Transcription in the dorsal pontine tegmentum was found to be necessary to maintain the long lasting bladder overactivity caused by cerebral infarction.
1. Fifty-five intact and six baroreceptor denervated and vagotomized cats of either sex were anaesthetized intraperitoneally with urethane (400 mg/kg) and alpha-chloralose (40 mg/kg). Responses of the systemic arterial pressure (SAP), mean SAP (MSAP) and sympathetic vertebral nerve (VNA) and renal nerve activities (RNA) were recorded. 2. In intact animals, monosodium L-glutamate (Glu, 0.1 mol/L, 50 nL) was microinjected into pressor areas of the locus coeruleus (LC), gigantocellular tegmental field (GTF), rostral ventrolateral medulla (RVLM) and dorsomedial medulla (DM), and the depressor areas of caudal ventrolateral medulla (CVLM). The induced actions were compared before and after microinjection of either glutamate antagonists, glutamate diethylester (GDEE, 0.5 mol/L, 50-100 nL), a competitive AMPA receptor blocker, or 2-amino-5-phosphonovaleric acid (D-AP5, 0.025 mol/L, 50-100 nL), a competitive N-methyl-D-aspartate (NMDA) receptor blocker. GDEE completely blocked the increases of SAP and VNA elicited from all pressor areas. D-AP5 only partially blocked the pressor but slightly blocked VNA and RNA responses from LC, GTF and DM, particularly those from RVLM. Neither GDEE nor D-AP5 blocked the depressor responses of SAP and two nerve activities elicited from CVLM. 3. In baroreceptor denervated animals, NMDA (2 mmol/L, 50-100 nL) and AMPA (0.2 mmol/L, 50-100 nL) were micro-injected into the same pressor areas of GTF, RVLM and DM and the depressor area of CVLM responsive to Glu activation (0.1 mol/L, 30 nL). In RVLM, DM and CVLM, the results of either NMDA or AMPA were similar to those induced by Glu. However, in GTF, microinjection of either NMDA or AMPA did not induce similar responses to Glu. This suggests that the nature of GTF may differ from RVLM and DM. 4. The above results suggest that the Glu-induced pressor responses from LC, GTF, DM and especially RVLM, are primarily mediated through AMPA receptors. The Glu-induced depressor responses from CVLM may not be predominantly mediated by either AMPA or NMDA receptors. 5. In both baroreceptor-intact and -denervated cats stimulation of the pressor areas often produced an increase of VNA and a decrease of RNA, while in the depressor CVLM decreased both VNA and RNA. The VNA, but not RNA were positively correlated with the pressor responses, while both VNA and RNA were positively correlated with the depressor responses. This may suggest that neurons of the sympathetic vertebral and renal nerves are topographically organized in the brain.
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