The organization of the efferent projections of the pedunculo-pontine tegmental nucleus to the dog pallidum

The study of pedunculo-pontine-pallidum projections in the dog's brain, which was performed using the method of retrograde axonal transport, has demonstrated the projections of a compact part (PPNc) and the lateral area of a diffuse part (PPNd) of midbrain pedunculo-pontine tegmental nucleus (PPN) to the globus pallidus, nucleus entopeduncularis and the ventral pallidum. PPNd medial area adjacent to decussation of the superior cerebellar peduncules, which is distinguished in other animals as the mesencephalic extrapiramydal area (MEA), projects only to the globus pallidus. In the dog, this tegmental area is not the major source of projections to striopallidum, therefore it appears not to be valid to distinguish it as an individual structure, it is reasonable to indicate only a topical organization PPNd projections to the pallidum. It was detected that the structures of pallidum received the projections from both cholinergic and non cholinergic initial PPN neurons.     

Organization of the efferent projections of the pedunculopontine tegmental nucleus of the midbrain of the dog pallidum

Studies of the pedunculopontinopallidal projections of the dog brain based on the retrograde axonal transport of horseradish peroxidase demonstrated that the compact zone (PPNc) and the lateral area of the diffuse zone (PPNd) of the pedunculopontine tegmental nucleus (PPN) of the midbrain project to the globus pallidus, entopeduncular nucleus, and ventral pallidum. The medial area of the PPNd, adjacent to the chiasm of the upper cerebellar peduncles and seen in other animals as the mesencephalic extrapyramidal area (MEA), projects only to the globus pallidus. In dogs, this area of the tegmentum is not a major source of projections to the striopallidum, such that it is inappropriate to regard it as a separate structure, comment being restricted to the topical organization of PPNd projections to the pallidum. Projection fibers to pallidal structures arise from both cholinergic and non-cholinergic PPN neurons. __________ Translated from Morfologiya, Vol. 127, No. 2, pp. 19–23, March–April, 2005.     

Descending brainstem projections of the pedunculopontine tegmental nucleus in the rat

Summary Descending brainstem projections from the pedunculopontine tegmental nucleus (PPN) were studied in the rat by use of the anterograde tracerPhaseolus vulgaris-leucoagglutinin (PHA-L) and the retrograde tracer lectin-conjugated horseradish peroxidase (HRP-WGA). Results of these experiments demonstrated prominent bilateral projections to the pontomedullary reticular nuclei, but direct connections to the motor and sensory nuclei of the cranial nerves could not be ascertained. The PPN fibers terminated mainly in the pontine reticular nuclei oralis and caudalis and in ventromedial portions (pars alpha and pars ventralis) of the gigantocellular reticular nucleus. A smaller number of labeled fibers distributed to more dorsal regions of the gigantocellular nucleus, lateral paragigantocellular, ventral reticular nucleus of the medulla and lateral reticular nucleus. Although a significant number of PHA-L labeled fibers was seen in two cases in the contralateral medial portion of the facial nucleus, and all cases exhibited a sparse predominantly ipsilateral projection to the lateral facial motor neurons, the retrograde tracing experiments have revealed that these facial afferents originated in the nuclei surrounding the PPN. The results are discussed in the context of PPN involvement in motor functions. It is suggested that the PPN may participate in a complex network involved in the orienting reflex.Abbreviations Am ambiguus nucleus - AP area postrema - Ac 7 accessory facial nucleus - asc 7 ascending fibers, facial nerve - CG central gray - Cnf cuneiform nucleus - Cu cuneate nucleus - cp cerebral peduncle - g7 germ facial nerve - Gi gigantocellular reticular nucleus - GiA gigantocellular reticular nucleus, pars alpha - GiV gigantocellular reticular nucleus, pars ventralis - Gr gracile nucleus - IC inferior colliculus - icp inferior cerebellar peduncle - IO inferior olive - IRt intermediate reticular nucleus - KF Kölliker-Fuse nucleus - LC locus coeruleus - ll lateral lemniscus - vsc ventral spinocerebellar tract - xscp decussation of superior cerebellar peduncle - 3 oculomotor nucleus - 4 trochlear nucleus - 6 abducens nucleus - 5n trigeminal nerve - 7 facial nucleus - 7n facial nerve - 10 dorsal motor nucleus of vagus - 12 hypoglossal nucleus - MPB medial parabrachial nucleus - MVe medial vestibular nucleus - PCRt parvicellular reticular nucleus - PN pontine nucleus - PPNe pedunculopontine tegmental nucleus, pars compacta - PPNd pedunculopontine tegmental nucleus, pars dissipata - Pr5 principal sensory trigeminal nucleus - py pyramidal tract - pyx pyramidal decussation - Rmes mesencephalic reticular nucleus - RN red nucleus - RPc reticularis pontis caudalis nucleus - Rpo reticularis pontis oralis nucleus - RR retrorubral nucleus - RRF retrorubral field rs rubrospinal tract - SC superior colliculus - scp superior cerebellar peduncle - LPB lateral parabrachial nucleus - LPGi lateral paragigantocellular reticular nucleus - LRt lateral reticular nucleus - LSO lateral superior olive - LVe lateral vestibular nucleus - MdD medullary reticular nucleus, dorsal - MdV medullary reticular nucleus, ventral - Me5 mesencephalic trigeminal nucleus - me5 mesencephalic trigeminal tract - ml medial lemniscus - mlf medial longitudinal fasciculus - Mo5 motor trigeminal nucleus - SNc substantia nigra, pars compacta - SNr substantia nigra, pars reticulata - SO superior olive - Sol nucleus of the solitary tract - sol solitary tract - sp5 spinal trigeminal tract - Sp5o spinal trigeminal nucleus, pars oralis - SPTg subpeduncular tegmental nucleus - SpVe spinal vestibular nucleus - Tz nucleus of the trapezoid body - tz trapezoid body - VLL ventral nucleus of the lateral lemniscus This paper is dedicated to Professor Fred Walberg on the occasion of his 70th birthday.     

Structural organization of pedunculopontine tegmental nucleus in the dog's midbrain

The aim of this study was to determine the borders of pedunculopontine tegmental nucleus (PPN) in the dog's brain and to describe its individual substructures on the basis of the cytoarchitectonic study of this nucleus. Using the methods of Nissl, Kluver-Barrera and histochemical demonstration of NADPH-diaphorase, which is a selective marker of cholinergic neurones of tegmental area, the analysis of fiber organization, morphological types of neurons and density of their distribution in PPN was carried out. As a result, mapping this nucleus in dog's brain was performed and the borders of its parts including a compact and a diffuse one were described. It was not possible to distinguish mesencephalic extrapyramidal area from the general composition of PPN.     

Spatial organization of the thalamic projections in the dog striatum

Using the method based on retrograde transport of markers injected into different segments of caudate and accumbent nuclei and putamen peculiarities of labelled neurons distribution in thalamic nuclei of the dog brain were studied. Zones of projection of motor and limbic thalamic nuclei and overlapping of terminal fields of fibres projection neurons of thalamic nuclei that function in different systems were demonstrated in the striatum. Comparative analysis of thalamostriatal projections organization in dogs, cats and monkeys allowed to reveal certain diversities in their construction as well as similarities.     

Deep brain stimulation of the pedunculopontine tegmental nucleus may influence renal function

Deep brain stimulation of the pedunculopontine tegmental nucleus (PPTg) had usually been reported to improve the symptoms of advanced Parkinson’s disease. Previous studies showed that neurons in the PPTg involved in the control of the sympathetic outflow to the kidneys. Our recent studies using transneuronal labeling pseudorabies virus (PRV)-614 supported the sympathetic nature of the caudal PPTg. We propose a hypothesis that deep brain stimulation of the PPTg may influence renal function by serotonergic and catecholaminergic pathways. Because PRV-614/tryptophan hydroxylase and PRV-614/tyrosine hydroxylase double-labeled neurons in the compact parts of PPTg (cpPPTg) were not detected, deep brain stimulation of the cpPPTg might not influence renal function.     

Respiratory pattern modulation by the pedunculopontine tegmental nucleus

This study demonstrates respiratory modulation caused by stimulation of the pedunculopontine tegmental nucleus (PPT), a structure not classically included in the pontine respiratory neuronal network. The long-lasting increase in variability of respiratory parameters following glutamate microinjection into PPT in anesthetized, spontaneously breathing Sprague Dawley rats was more pronounced under ketamine than nembutal anesthesia. The induced respiratory perturbations were characterized by intermittent apneas and increased variability of expiratory (TE) and total (TT) breath durations in all animals. Although the baseline spontaneous breathing patterns (mean values of all respiratory parameters and their variabilities) were equivalent under ketamine and nembutal anesthesia, different anesthetic agents did affect respiratory responses to PPT stimulation by glutamate in terms of latency, duration, and structure. We conclude that glutamatergic stimulation of PPT has a significant impact on the brainstem respiratory pattern generator.     

The pedunculopontine tegmental nucleus and responding for sucrose reward

Pedunculopontine tegmental nucleus (PPTg) lesions in rodents lead to increased sucrose consumption, but the psychological deficit behind this remains uncertain. To understand better the relationship between consumption of, and motivation for, sucrose, the authors trained rats to traverse a runway for 20% or 4% sucrose solution; after 7 days, concentrations were reversed. Control rats consumed more 20% than 4% sucrose solution and promptly altered run times in response to concentration change. PPTg-lesioned rats consumed normal quantities of 4% but more 20% sucrose solution than controls and took longer to alter their runway time following the concentration change. These data suggest that lesions of the PPTg do not alter motivation per se and might be better understood as inducing a response selection deficit. ((c) 2006 APA, all rights reserved).     

Cholinergic projections to the substantia nigra from the pedunculopontine and laterodorsal tegmental nuclei

The cholinergic innervation of the compact and reticular parts of the substantia nigra in the rat was investigated by use of highly sensitive retrograde and anterograde tract-tracing methods in combination with choline acetyltransferase immunohistochemistry. The fluorescent tracers True Blue, propidium iodide, or fluorogold were infused preferentially into either nigral subnucleus. Cells positive for choline acetyltransferase and retrograde tracer were found in both the pedunculopontine and laterodorsal tegmental nuclei, although considerably more double-labeled somata were observed in the former than in the latter component of the pontomesencephalotegmental cholinergic complex. Approximately 2-3 times more cholinergic cells were labeled in the peduculopontine and laterodorsal tegmental nuclei when tracer injections were centered in the compact nigral subdivision than when infusions of about the same size were confined totally to the reticular part. Infusions of the anterogradely transported tracer Phaseolus vulgaris leucoagglutinin into the pontomesencephalotegmental cholinergic complex resulted in uptake and transport of that label to both nigral subnuclei, and some of the Phaseolus vulgaris leucoagglutinin-accumulating somata and proximal processes also demonstrated choline acetyltransferase-like immunoreactivity. The Phaseolus vulgaris agglutinin-labeled entities in the substantia nigra exhibited terminal-like profiles that were reminiscent of the pattern of nigral choline acetyltransferase-positive puncta demonstrated immunohistochemically by use of nickel ammonium sulfate enhancement of the final reaction product in the avidin-biotin procedure. These observations strongly support the contention that the pontomesencephalotegmental cholinergic complex is the major source of cholinergic projections to both the compact and reticular portions of the rat substantia nigra.     

Spatial organization of amygdaloid, nigral, and tegmental projections in the dog neostriatum

Axonal transport of retrograde markers was used to study the distribution of projections from functionally diverse subcortical structures (the substantia nigra, the ventral tegmental area, and the amygdaloid body) in the caudate nucleus and putamen of the dog. Striatal structures were found to contain regions receiving projections from limbic structures or formations involved largely in motor acts. These structures also contained regions with concordant terminal fields from neurons of these and other functional structures. These results provide a morphological basis for interactions of information currents of different functional significance in the striatum, as well as providing a foundation for their functional heterogeneity. These allow a deeper understanding of their roles in the systems organization of behavior and integrative brain activity. Laboratory for the Physiology of Higher Nervous Activity, I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Makarov Bank, 199034 St. Petersburg, Russia. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 83, No. 1–2, pp. 53–61, January–February, 1997.     

Cholinergic and non-cholinergic neurons in the rat pedunculopontine tegmental nucleus

Summary Choline acetyltransferase immunhistochemistry was employed at light and electron microscopic levels in order to determine the distribution of cholinergic neurons in two subdivisions of the rat pedunculopontine tegmental nucleus that were previously defined on cytoarchitectonic grounds, and to compare the synaptic inputs to cholinergic and non-cholinergic somata in the subnucleus dissipatus, which receives major input from the substantia nigra. Large cholinergic neurons were found in both the pars compacta and the pars dissipata of the pedunculopontine nucleus. However, they were intermingled with non-cholinergic neurons and did not respect the cytoarchitectural boundaries of the nucleus. Ultrastructural study showed that all cholinergic neurons in the subnucleus dissipatus exhibited similar features. The majority had large somata (largest diameter 20 m) containing abundant cytoplasmic organelles and nuclei displaying a few shallow invaginations. Synaptic terminals on the cholinergic cell bodies were scarce and unlabeled boutons containing spherical synaptic vesicles and establishing asymmetric synaptic junctions were the dominant type. In contrast, the non-cholinergic neurons presented prominent differences in the size of their somata as well as in the distribution of axosomatic synapses. Two almost equally represented classes of non-cholinergic neurons which are referred to as large (largest diameter 20 m) and small (largest diameter <20 m) were recognized. Large non-cholinergic cell bodies were ultrastructurally similar to the cholinergic ones, but they received rich synaptic input by unlabeled nerve terminals which contained pleomorphic vesicles and were engaged in symmetric synaptic junctions. Small non-cholinergic cell bodies were characterized by deeply invaginated nuclei surrounded by a narrow rim of cytoplasm, and were often found near or in direct apposition to the cholinergic somata. Their major input consisted of axosomatic boutons containing round synaptic vesicles. These results demonstrate that cells in the pedunculopontine tegmental nucleus are differentiated with regard to their axosomatic synaptic inputs which may influence their firing properties. Furthermore, they support previous suggestions that nigral afferents may be preferentially distributed to a subpopulation of the pedunculopontine neurons.Abbreviations cp cerebral peduncle - CG central gray - CNF cunei-form nucleus - LPB lateral parabrachial nucleus - ml medial lemn-iscus - MPB medial parabrachial nucleus - me5 mesencephalic tri-geminal tract - Me5 nucleus of the mesencephalic tract of the trige-minal nerve - Mo5 motor trigeminal nucleus - PPNc pedunculo-pontine nucleus, subnucleus compactus - PPNd pedunculopontinenucleus subnucleus dissipatus - rs rubrospinal tract - RPo pontinereticular nucleus, oral portion - RR retrorubral nucleus - RRF re-trorubral field - scp superior cerebellar peduncle - SNr substantianigra, pars reticulata - SPTg subpeduncular tegmental nucleus - 3n oculomotor nerve     

Structural basis of the involvement of the striopallidum and pedunculopontine tegmental nucleus in the organization of adaptive behavior

Retrograde axonal transport was used to study the organizational characteristics of the afferent and efferent projection systems of individual substructures of the pedunculopontine tegmental nucleus and the functionally diverse (motor, limbic) areas of structures in the striopallidum. The structural bases of the conduction of functionally diverse information and its integration in the basal ganglia system and tegmental area were evaluated. The morphological data obtained here aid our understanding of the morphofunctional bases of the interaction of these structures and their involvement in adaptive behavior. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 92, No. 7, pp. 777–787, July, 2006.     

Glutamate and GABA modulate dopamine in the pedunculopontine tegmental nucleus

The pedunculopontine tegmental nucleus (PPTg) has an important anatomical position connecting basal ganglia and limbic systems with motor execution structures in the pons and spinal cord. It receives glutamatergic and GABAergic input and has additional reciprocal connections with mesencephalic dopaminergic neurons, suggesting that the PPTg plays a key role in frontostriatal information processing. In vivo microdialysis in freely moving rats, in combination with behavioral analysis, was used in this study to investigate whether the dopaminergic input can be modulated at the level of the PPTg via N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) or GABA_B receptors. Stimulation of the GABA_B receptor decreased dopamine release in the PPTg while that of the AMPA and NMDA receptors increased it. A time-related comparison of the effects of NMDA (0.75 and 1 mM) and AMPA (50 and 25 μM) revealed a more long-lasting effect after AMPA stimulation than after NMDA. However, only the infusion of the GABA_B receptor agonist baclofen (100 and 200 μM) stimulated stereotyped behavior (e.g. sniffing, digging or head movements) and contralateral circling. This study clearly demonstrates that GABAergic as well as glutamatergic terminals in the PPTg are critically involved in the modulation of the dopamine system. Moreover, a decrease in PPTg dopamine via GABA_B receptor stimulation seems to be behaviorally relevant. Electronic Publication     

Mesopontine rostromedial tegmental nucleus neurons projecting to the dorsal raphe and pedunculopontine tegmental nucleus: psychostimulant-elicited Fos expression and collateralization

The mesopontine rostromedial tegmental nucleus (RMTg) is a GABAergic structure in the ventral midbrain and rostral pons that, when activated, inhibits dopaminergic neurons in the ventral tegmental area and substantia nigra compacta. Additional strong outputs from the RMTg to the pedunculopontine tegmental nucleus pars dissipata, dorsal raphe nucleus, and the pontomedullary gigantocellular reticular formation were identified by anterograde tracing. RMTg neurons projecting to the ventral tegmental area express the immediate early gene Fos upon psychostimulant administration. The present study was undertaken to determine if neurons in the RMTg that project to the additional structures listed above also express Fos upon psychostimulant administration and, if so, whether single neurons in the RMTg project to more than one of these structures. We found that about 50% of RMTg neurons exhibiting retrograde labeling after injections of retrograde tracer in the dorsal raphe or pars dissipata of the pedunculopontine tegmental nucleus express Fos after acute methamphetamine exposure. Also, we observed that a significant number of RMTg neurons project both to the ventral tegmental area and one of these structures. In contrast, methamphetamine-elicited Fos expression was not observed in RMTg neurons labeled with retrograde tracer following injections into the pontomedullary reticular formation. The findings suggest that the RMTg is an integrative modulator of multiple rostrally projecting structures.     

c-Fos expression after deep brain stimulation of the pedunculopontine tegmental nucleus in the rat 6-hydroxydopamine Parkinson model

Deep brain stimulation (DBS) is used to alleviate motor dysfunction in Parkinson's disease (PD). The pedunculopontine nucleus (PPN) may be a potential target for severe freezing and postural instability with 25 Hz stimulation being considered more effective than 130 Hz stimulation. Here we evaluated the expression of c-Fos after 25 Hz and 130 Hz DBS of the pedunculopontine tegmental nucleus (PPTg, i.e., the rodent equivalent to the human PPN) in the rat 6-hydroxydopamine (6-OHDA) PD model.Anaesthetized male Sprague Dawley rats with unilateral 6-OHDA-induced nigrostriatal lesions were stimulated with 25 Hz, 130 Hz, or 0 Hz sham-stimulation for 4 h by electrodes implanted into the ipsilateral PPTg. Thereafter the distribution and number of neurons expressing the immediate early gene c-Fos, a marker for acute neuronal activity, was assessed.DBS of the PPTg induced strong ipsilateral c-Fos expression at the stimulation site, with 25 Hz having a more marked impact than 130 Hz. Additionally, c-Fos was strongly expressed in the central gray. In the dorsal part expression was stronger after 25 Hz stimulation, while in the medial and ventral part there was no difference between 25 Hz and 130 Hz stimulation. Expression in the basal ganglia was negligible.In the rat 6-OHDA PD model stimulation of the PPTg did not affect c-Fos expression in the basal ganglia, but had a strong impact on other functional circuitries. PPN stimulation in humans might therefore also have an impact on other systems than the motor system.     

Postnatal development of cholinergic afferents from the pedunculopontine tegmental nucleus to the lateralis medialis-suprageniculate nucleus of the feline thalamus

The lateralis medialis-suprageniculate nuclear complex (LM-Sg) has been shown to receive cholinergic fibers from the pedunculopontine tegmental nucleus (PPT). The majority of terminals of these cholinergic fibers make simple synaptic contact with dendritic profiles, whereas some make contacts with the dendrites of projection neurons and GABAergic interneurons forming a glomerular synaptic complex. In the present study, we investigate the postnatal development of glomerular synaptic complexes in the LM-Sg in association with terminals of the PPT-thalamic projection fibers. We examined the postnatal development of cholinergic innervation as well as GABAergic interneuron innervation in the LM-Sg using antibodies against ChAT and GABA, respectively. Although choline acetyltransferase (ChAT)-positive neurons already exist in the PPT at birth (P0), ChAT-positive fibers in the LM-Sg were observed only after P7. These ChAT-positive fibers gradually increased in number, and almost reached the adult level by postnatal day 28 (P28). GABA-positive interneurons were scattered throughout the LM-Sg at P0, increased in size gradually and reached adult size by P14. Immature glomerulus-like synaptic arrangements appeared at P14. Definite glomeruli, in which ChAT-positive terminals are present, were observed at P28. These results emphasize that interneurons in the LM-Sg grow by P14, and then make neural circuits with cholinergic innervation within the glomerulus by 3–4 weeks.     

The pedunculopontine tegmental nucleus: a second cholinergic source for frequency-specific auditory plasticity

Cholinergic modulation is essential for many brain functions and is an indispensable component of the prevalent models attempting to understand the neural mechanism responsible for learning-induced auditory plasticity. Unlike the cholinergic basal forebrain, the cholinergic pedunculopontine tegmental nucleus (PPTg) has received little attention. This study was designed to confirm whether the PPTg enables frequency-specific plasticity in the ventral division of the medial geniculate body of the thalamus (MGBv). Using the mouse model, we paired electrical stimulation of the PPTg with tone stimulation to help define the role of the PPTg. The receptive fields of MGBv neurons were examined before and after the paired stimulation; they were quantified in this study by best frequency (BF), response threshold, dynamic range, and spike number. We found that the electrical stimulation of the PPTg together with a tone presentation shifted the BFs of MGBv neurons upward when the frequency of the paired tone was higher than that of the control BF. Similarly, the BFs shifted downward when the frequency of the paired tone was lower than that of the control BF. The BFs of MGBv neurons, however, remained unchanged when the frequency of the paired tone was the same as that of the control BF. There was a linear relationship between the BF shift of MGBv neurons and the difference between the frequency of the paired tone and the control BF of MGBv neurons. Highly frequency specific changes were also observed in the response threshold, dynamic range, and spike number. This frequency-specific plasticity was largely eliminated by the microinjection of the muscarinic receptor antagonist atropine into the MGBv before the paired stimulation. Our findings suggest that the PPTg, like the cholinergic basal forebrain, is an important cholinergic source that enables frequency-specific plasticity in the central auditory system.     

Behavioural sensitisation to repeated d-amphetamine: effects of excitotoxic lesions of the pedunculopontine tegmental nucleus

The pedunculopontine tegmental nucleus (PPTg) interacts with anatomical systems thought to be involved in mediating sensitisation of the locomotor response to repeated d-amphetamine. The PPTg has direct and indirect connections with the nucleus accumbens and prefrontal cortex, and also influences midbrain dopamine activity through direct projections to substantia nigra and ventral tegmental area. In this experiment, the development of behavioural sensitisation to the locomotor stimulant effects of repeated d-amphetamine was examined in rats bearing excitotoxic lesions of the PPTg, and sham-lesioned controls. Rats were given repeated d-amphetamine (1.5 mg/kg i.p.) treatment in an on-off procedure, with saline and d-amphetamine given on alternate days, such that rats received a total of seven d-amphetamine and seven saline treatments. Locomotor responses were measured in photocell cages. On the first day of d-amphetamine treatment, there was no difference between excitotoxin and sham-lesioned rats. Development of sensitisation to the locomotor stimulant effects of d-amphetamine was delayed in PPTg-lesioned rats, relative to the sham-lesioned control rats. However, there was no difference between lesion and control groups in the locomotion seen on saline-treatment days. These data suggest that the PPTg is involved in the development of behavioural sensitisation to the locomotor stimulant effects of repeated d-amphetamine, and indicate that traditional striatal circuitry models of the mechanisms underlying sensitisation should be extended to include the PPTg.     

The pedunculopontine nucleus

In an effort to account for a large number of reported functions mediated by a small portion of the midbrain, a hypothesis is advanced as a basis for discussion and not as established fact and is guided by reports from a large number of laboratories working on the same region but using widely disparate preparations. Overall, the hypothesized model suggests an underlying mechanism of action for what is essentially the ascending reticular activating system. The model proposed will hopefully be tested stringently in order to arrive at a better understanding of brain stem mechanisms modulating a host of rhythmic functions.     

Stimulation of the pedunculopontine tegmental nucleus may affect renal function by melanocortinergic signaling

Deep brain stimulation of the pedunculopontine tegmental nucleus (PPTg) has been reported to improve gait disturbance in animal models of Parkinsonism and among patients with Parkinson’s disease. Evidence suggests that neurons in the PPTg are involved in the control of the sympathetic outflow to the kidneys, and sympathetic regulation is a major component of central melanocortin action. Our recent studies using transneuronal labeling pseudorabies virus (PRV)-614 and melanocortin-4 receptor (MC4R)-green fluorescent protein (GFP) transgenic mice supported the melanocortinergic nature of the middle and caudal PPTg (mPPTg and cPPTg). Because PRV-614/MC4R-GFP double-labeled neurons in the mPPTg and cPPTg were detected, we propose a hypothesis that deep brain stimulation of the PPTg may influence renal function by the melanocortinergic pathway.