Projections of striatopallidal structures to the pedunculopontine nucleus of the tegmentum of the midbrain in dogs

A method based on retrograde axonal transport of horseradish peroxidase was used to study the striatopallidal afferent projections of the pendunculopontine nucleus of the midbrain (PPN) in dogs. The major source of these projections was found to be the pallidum, as both the compact and diffuse zones of this nucleus received projections from all of its structures: the entopeduncular nucleus, the globus pallidus, and the ventral pallidum. The striatal complex, specifically the nucleus accumbens, showed only occasional labeled neurons, projecting exclusively to the compact part of the PPN. Since the distribution of projection fibers arising from the functionally diverse territories of the striatopallidum and directed to individual structural subdivisions of the PPN showed no topical elements, identification of functionally specific (motor and limbic) areas of the PPN was not possible on the basis of the present analysis. __________ Translated from Morfologiya, Vol. 130, No. 6, pp. 30–34, November–December, 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     

Organization of ventral tegmental area projections to the ventral tegmental area-nigral complex in the rat

The ventral tegmental area (VTA) is a nodal link in reward circuitry. Based on its striatal output, it has been subdivided in a caudomedial part which targets the ventromedial striatum, and a lateral part which targets the ventrolateral striatum [Ikemoto S (2007) Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex. Brain Res Rev 56:27-78]. Whether these two VTA parts are interconnected and to what extent the VTA innervates the substantia nigra compacta (SNc) and retrorubral nucleus (RR) are critical issues for understanding information processing in the basal ganglia. Here, VTA projections to the VTA-nigral complex were examined in rats, using Phaseolus vulgaris leucoagglutinin (PHA-L) as anterograde tracer. The results show that the dorsolateral VTA projects to itself, as well as to the dorsal tier of the SNc and RR, largely avoiding the caudomedial VTA. The ventrolateral VTA innervates mainly the interfascicular nucleus. The components of the caudomedial VTA (the interfascicular, paranigral and caudal linear nuclei) are connected with each other. In addition, the caudomedial VTA (especially the paranigral and caudal linear nuclei) innervates the lateral VTA, and, to a lesser degree, the SNc and RR. The caudal pole of the VTA sends robust, bilateral projections to virtually all the VTA-nigral complex, which terminate in the dorsal and ventral tiers. Modest inputs from the medial supramammillary nucleus to ventromedial parts of the VTA-nigral complex were also identified. In double-immunostained sections, PHA-L-labeled varicosities were sometimes found apposed to tyrosine hydroxylase-positive neurons in the ventral mesencephalon. Overall, the results underscore that VTA projections to the VTA-nigral complex are substantial and topically organized. In general, these projections, like the spiralated striato-nigro-striatal loops, display a medial-to-lateral organization. This anatomical arrangement conceivably permits the ventromedial striatum to influence the activity of the lateral striatum. The caudal pole of the VTA appears to be a critical site for a global recruitment of the mesotelencephalic system.     

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 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.     

MC4R expression in pedunculopontine nucleus involved in the modulation of midbrain dopamine system

Background and objective: Separate studies have implicated the pedunculopontine tegmental nucleus (PPTg) in processing aversive stimuli to dopamine systems, and melanocortin-4 receptor (MC4R) are broadly expressed by the neurons in the PPTg, but the exact neurosubstrate underlying the regulation of dopamine systems by the central melanocortin pathway is poorly understood. Methods: In this study, the PPTg of 6 adult mice expressing green fluorescent protein (GFP) under the control of the MC4R promoter was detected by fluorescence immunohistochemistry. Results: A large number of GFP-positive neurons in the dissipated parts of PPTg (dpPPTg) were found, and approximately 50% of MC4R-GFP- positive neurons in the dpPPTg coexpressed tyrosine hydroxylase, a marker of dopamine neurons, indicating that they were dopaminergic. Conclusions: Our findings support the hypothesis that MC4R signaling in the dpPPTg may involve in the modulation of midbrain dopamine systems.     

The organization of the efferent projections of the pedunculopontine tegmental nucleus to the striatum of the dog brain

Using the method of retrograde axonal transport, the detailed study was performed to demonstrate the efferent projections of the individual substructures of the pedunculopontine tegmental midbrain nucleus to the functionally different segments of the striatal structures in the dog. The compact and diffuse parts of this nucleus were found to project to the segments of the putamen, caudate nucleus and nucleus accumbens which belong to both limbic and motor systems. The medial region of the diffuse part adjacent to the decussation of superior cerebellar peduncles (presumably midbrain extrapyramidal area), projected only to the dorsal segments of the caudate nucleus and the putamen belonging to motor system.     

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.     

Organization of Efferent Projections of the Pedunculopontine Nucleus of the Tegmentum of the Striatum in the Dog Brain

A method based on retrograde axonal transport was used to undertake detailed studies of the efferent projections of individual substructures of the pedunculopontine nucleus of the midbrain tegmentum to functionally diverse segments of striatal structures in dogs. The compact and diffuse zones of this nucleus were found to project to segments of the putamen, caudate nucleus, and nucleus accumbens, which are components of the limbic and motor systems. The medial part of the diffuse zone, adjacent to the decussation of the superior cerebellar peduncles (presumptively the mesencephalic extrapyramidal field) projected only to the dorsal segments of the caudate nucleus and putamen, which are parts of the motor system. __________ Translated from Morfologiya, Vol. 126, No. 6, pp. 11–15, November–December, 2004. Director: Doctor of Biological Sciences V. T. Shuvaev     

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.     

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.     

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     

Distinct types of non-cholinergic pedunculopontine neurons are differentially modulated during global brain states

The pedunculopontine nucleus (PPN) is critically involved in brain-state transitions that promote neocortical activation. In addition, the PPN is involved in the control of several behavioral processes including locomotion, motivation and reward, but the neuronal substrates that underlie such an array of functions remain elusive. Here we analyzed the physiological properties of non-cholinergic PPN neurons in vivo across distinct brain states, and correlated these with their morphological properties after juxtacellular labeling. We show that non-cholinergic neurons in the PPN whose firing is not strongly correlated to neocortical activity are highly heterogeneous and are composed of at least three different subtypes: (1) “quiescent” neurons, which are nearly silent during slow-wave activity (SWA) but respond robustly to neocortical activation; (2) “tonic firing” neurons, which have a stationary firing rate that is independent of neocortical activity across different brain states; and (3) “irregular firing” neurons, which exhibit a variable level of correlation with neocortical activity. The majority of non-cholinergic neurons have an ascending axonal trajectory, with the exception of some irregular firing neurons that have descending axons. Furthermore, we observed asymmetric synaptic contacts within the PPN arising from the axon collaterals of labeled neurons, suggesting that excitatory, non-cholinergic neurons can shape the activity of neighboring cells. Our results provide the first evidence of distinct firing properties associated with non-cholinergic neuronal subtypes in the PPN, suggesting a functional heterogeneity, and support the notion of a local network assembled by projection neurons, the properties of which are likely to determine the output of the PPN in diverse behavioral contexts.     

Stereological estimates of dopaminergic, GABAergic and glutamatergic neurons in the ventral tegmental area, substantia nigra and retrorubral field in the rat

Midbrain dopamine neurons in the ventral tegmental area, substantia nigra and retrorubral field play key roles in reward processing, learning and memory, and movement. Within these midbrain regions and admixed with the dopamine neurons, are also substantial populations of GABAergic neurons that regulate dopamine neuron activity and have projection targets similar to those of dopamine neurons. Additionally, there is a small group of putative glutamatergic neurons within the ventral tegmental area whose function remains unclear. Although dopamine neurons have been intensively studied and quantified, there is little quantitative information regarding the GABAergic and glutamatergic neurons. We therefore used unbiased stereological methods to estimate the number of dopaminergic, GABAergic and glutamatergic cells in these regions in the rat. Neurons were identified using a combination of immunohistochemistry (tyrosine hydroxylase) and in situ hybridization (glutamic acid decarboxylase mRNA and vesicular glutamate transporter 2 mRNA). In substantia nigra pars compacta 29% of cells were glutamic acid decarboxylase mRNA-positive, 58% in the retrorubral field and 35% in the ventral tegmental area. There were further differences in the relative sizes of the GABAergic populations in subnuclei of the ventral tegmental area. Thus, glutamic acid decarboxylase mRNA-positive neurons represented 12% of cells in the interfascicular nucleus, 30% in the parabrachial nucleus, and 45% in the parainterfascicular nucleus. Vesicular glutamate transporter 2 mRNA-positive neurons were present in the ventral tegmental area, but not substantia nigra or retrorubral field. They were mainly confined to the rostro-medial region of the ventral tegmental area, and represented approximately 2-3% of the total neurons counted ( approximately 1600 cells). These results demonstrate that GABAergic and glutamatergic neurons represent large proportions of the neurons in what are traditionally considered as dopamine nuclei and that there are considerable heterogeneities in the proportions of cell types in the different dopaminergic midbrain regions.     

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.     

Excitotoxic lesions of the pedunculopontine tegmental nucleus in rats impair performance on a test of sustained attention

Recent research has suggested that the pontomesencephalic tegmentum might be an important part of a network underlying sustained attention. The largest structure of the pontomesencephalic tegmentum is the pedunculopontine tegmental nucleus, which has ascending connections to thalamus and with corticostriatal systems. In this experiment we examined the performance of rats following bilateral excitotoxic lesions of the pedunculopontine tegmental nucleus on a test of sustained attention previously used to examine frontal cortical function. After an initial period of darkness, the rats had to attend continuously to a dim stimulus light that would, at unpredictable intervals, become transiently brighter. During this period of increased stimulus brightness the rats could press a lever to obtain a food reward. Rats were trained to a criterion level of performance before lesions were made. After surgery, sham lesioned rats (n=7) resumed accurate responding, with an average successful detection rate of ~70%. Pedunculopontine lesioned rats (n=7), however, only achieved a successful detection rate of ~40%. When the duration of the bright target stimulus was increased from 1.5 to 4 s, the performance of the pedunculopontine lesioned rats significantly improved. The observation that an increase in brightness duration caused a marked improvement in lesioned rats performance suggests strongly that the impairment was in attention rather than motor ability or simple sensory processing. These data are taken to be consistent with the hypothesis that the pedunculopontine tegmental nucleus is an important part of a network maintaining attention.     

电刺激大鼠黑质网状部对脚桥核神经元自发放电的影响

目的:观察电刺激大鼠黑质网状部(substantia nigra pars reticulata,SNr)对脚桥核(pedunculopontine nucleus,PPN)神经元自发放电活动的影响,进一步探讨脑内电刺激治疗帕金森病(Parkinson's disease,PD)的机制.方法:应用细胞外记录方法观察不同...     

Organization and efferent projections of nucleus tegmenti pedunculopontinus pars compacta with special reference to its cholinergic aspects

In an attempt to evaluate the cellular organization and efferent projections of the nucleus tegmenti pedunculopontinus pars compacta, several experiments were performed in the rat. From measurements of neurons in the nucleus tegmenti pedunculopontinus pars compacta in Nissl-stained sections, the nucleus was observed to contain many large neurons which made it possible to demarcate this nucleus from surrounding pontomesencephalic reticular formation. Two other neuronal populations, medium and small neurons, were also seen in the nucleus tegmenti pedunculopontinus pars compacta. Detailed measurements showed that 90% by volume of all neurons in the nucleus tegmenti pedunculopontinus pars compacta were large and medium-sized neurons. After injections of [ ³H]leucine into the nucleus tegmenti pedunculopontinus pars compacta, transported label was observed in dorsally and ventrally coursing ascending fibers. The dorsally coursing fibers entered the centrolateral nucleus and centre median-parafascicular complex of the thalamus. The ventrally coursing fibers produced accumulation of silver grains in the ventral tegmental area, substantia nigra pars compacta, subthalamic nucleus, zona incerta and lateral hypothalamus. Crossed fibers of the nucleus tegmenti pedunculopontinus pars compacta were observed sparsely at the levels of the thalamus and posterior commissure, and to a greater degree through the supraoptic commissure of Meynert. Much less anterograde labeling was seen in the equivalent terminal sites on the contralateral side of the brain. By electron microscopic autoradiography major terminal sites of axons of the nucleus tegmenti pedunculopontinus pars compacta were examined in rats injected with [ ³H]leucine in the nucleus tegmenti pedunculopontinus pars compacta and later injected with horseradish peroxidase in the striatum and pallidum. Statistical data showed preferential radiolabeling of terminals forming asymmetrical synaptic contact with dendrites in the centrolateral nucleus, centre median-parafascicular complex and subthalamic nucleus. Apparent terminations in the substantia nigra pars compacta proposed in earlier studies and shown in the present light microscopic autoradiograms were not supported by this ultrastructural analysis. Several radiolabeled terminals of the asymmetrical type contacting horseradish peroxidase labeled dendrites in the thalamus confirmed direct input from the nucleus tegmenti pedunculopontinus pars compacta to the thalamostriate projection neurons. [ ³H]choline injections into the thalamus and subthalamic nucleus produced retrograde perikaryal labeling of large neurons in the nucleus tegmenti pedunculopontinus pars compacta. These neurons were unlabeled after [ ³H]choline injections in the substantia nigra. Other findings suggested retrograde transport of [ ³H]choline through cholinergic terminals as well as cholinergic fibers of passage. These data suggested a selective uptake mechanism for cholinergic fibers of passage.The results emphasize the cholinergic nature of the nucleus tegmenti pedunculopontinus pars compacta innervation of the thalamus and subthalamic nucleus. Large neurons in the nucleus tegmenti pedunculopontinus pars compacta seem responsible for this cholinergic innervation and probably provide the axon terminals making asymmetrical synapses in the thalamus and subthalamic nucleus as described above. In addition, large neurons as well as medium and small ones in the nucleus tegmenti pedunculopontinus pars compacta whose transmitters and exact destinations remain unknown send a number of axons through the supraoptic commissure of Meynert to innervate the contralateral subthalamic nucleus.     

电刺激大鼠伏隔核对腹侧苍白球神经元自发放电的影响

目的:研究电刺激大鼠伏隔核(nucleus accumbens,NAC)对腹侧苍白球(ventral pallidum,VP)神经元放电的影响,探索电刺激NAC治疗药物成瘾的机制。方法:本实验应用细胞外记录方法观察不同频率电刺激(强度0.4mA,波宽0.06ms,时程5s,频率5,10,20,50,80,100,130,150和200Hz)大鼠NAC对VP神经元放电的影响。结果:刺激频率低于20Hz时,大多数VP神经元的放电频率无变化,电刺激频率大于20Hz可使大多数VP神经元的放电频率降低。结论:本研究提示高频刺激NAC对药物依赖可能有治疗作用。