Nucleus Pontis Research Articles

Autoradiographic analysis of ascending projections from the pontine and mesencephalic reticular formation and the median raphe nucleus in the rat.

Ascending projections from the medial pontine reticular formation, the mesencephalic reticular formation, and the median raphe nucleus were examined using the autoradiographic technique. The majority of the ascending fibers labeled after injections of [3H]-leucine into the nucleus pontis caudalis (RPC) course through the brainstem within the tracts of Forel (tractus fasciculorum tegmenti of Forel) and directly ventral to them. At the caudal diencephalon, Forel's bundle divides into dorsal and ventral components bound primarily for the dorsal thalamus and the subthalamus, respectively. RPC fibers project to several regions involved in oculomotor/visual functions. These include the abducens nucleus, the intermediate gray layer of the superior colliculus (SCi), the anterior pretectal nucleus (APN), the ventral lateral geniculate nucleus (LGNv), and regions of the central gray directly bordering the oculomotor nucleus, the interstitial nucleus of Cajal, and the nucleus of Darkschewitsch. Few, if any, fibers from RPC (or from nucleus pontis oralis-RPO) terminate within the oculomotor nucleus proper. Other sites receiving heavy projections from the RPC include adjacent regions of the pontomesencephalic reticular formation (RF), the parafascicular (PF) and central lateral (CL) nuclei of the thalamus and the fields of Forel/zona incerta (FF-ZI). RPO fibers also ascend predominantly in Forel's bundle. Other ascending tracts for these fibers are the medial longitudinal fasciculus and the central tegmental tract (CTT). RPO fibers distribute significantly to the same structures of the oculomotor/visual system receiving projections from RPC. The RPO projections to the SCi and the APN are particularly pronounced. RPO fibers terminate heavily in several nuclei located ventrally within the rostral midbrain/caudal diencephalon. These include major dopamine-containing cell groups (the retrorubral nucleus, the ventral tegmental area, and the substantia nigra-pars compacta) as well as the interpeduncular nucleus, the lateral mammillary nucleus, and the supramammillary nucleus. Other prominent targets for RPO fibers include the mesencephalic RF, specific regions of the central gray, the PF, the CL, the paracentral and central medial nuclei of the thalamus, and the FF/ZI. The major bundle of the ascending fibers labeled after injections of the mesencephalic reticular formation (MRF) travels within the CTT in a position just lateral to the central gray, but a significant number of labeled axons also course in Forel's bundle.(ABSTRACT TRUNCATED AT 400 WORDS)

Frontal eye field efferents in the macaque monkey: II. Topography of terminal fields in midbrain and pons

Frontal eye field (FEF) projections to the midbrain and pons were studied in nine macaque monkeys that were used to study FEF projections to the striatum and thalamus (Stanton et al.: J. Comp. Neurol. 271:473-492, '88). Injections of tritiated amino acids or WGA-HRP were made into FEF cortical locations where low-level microstimulation (less than or equal to 50 microA) elicited saccadic eye movements, and anterograde axonal labeling was mapped. The injections were made into the anterior bank of the arcuate sulcus from dorsomedial sites where large saccades were evoked (lFEF) to ventrolateral sites where small saccades were evoked (sFEF). The largest terminal fields of FEF fibers were located in the ipsilateral superior colliculus (SC). Projections to SC were topographically organized: lFEF sites projected to intermediate and deep layers of caudal SC, sFEF sites projected to intermediate and superficial layers of rostral SC, and FEF sites between these extremes projected to intermediate locations in SC. Patches of terminal labeling were located ipsilaterally in the lateral mesencephalic reticular formation near the parabigeminal nucleus and the ventrolateral pontine reticular formation. These patches were larger from lFEF injections. Small, dense terminal patches were seen in the ipsilateral pontine gray, mostly along the medial and dorsal borders of these nuclei but occasionally in central and dorsolateral regions. Patches of label like those in the pontine nuclei were located ipsilaterally in the reticularis tegmenti pontis nucleus in lFEF cases and bilaterally in sFEF cases. Small terminal patches were found in the nucleus of Darkschewitsch and dorsal and medial parts of the parvicellular red nucleus in most FEF cases. In the pretectal region, labeled terminal patches were consistently found in the nucleus limitans of the posterior thalamus, but we could not determine if label in the nucleus of the pretectal area and dorsal parts of the nucleus of the posterior commissure marked axon terminals or fibers of passage. We found small, lightly labeled terminal patches in the pontine raphe between the rootlets of the abducens nerve (three cases) or in the adjacent paramedian pontine reticular formation (one case). Omnipauser cells in this region are important in initiating saccades. In one sFEF case, very small patches of label were located in the supragenual nuclei anterior to the abducens nuclei and in the ipsilateral nucleus prepositus hypoglossi posterior to the abducens nucleus. Presaccadic burster neurons in the periabducens region are known to fire immediately before horizontal saccades.(ABSTRACT TRUNCATED AT 400 WORDS)

Frontal eye field efferents in the macaque monkey: I. Subcortical pathways and topography of striatal and thalamic terminal fields

Anterograde tracers (tritiated leucine, proline, fucose; WGA-HRP) were injected into sites within the frontal eye fields (FEF) of nine macaque monkeys. Low thresholds (less than or equal to 50 microA) for electrically evoking saccadic eye movements were used to locate injection sites in four monkeys. Cases were grouped according to the amplitude of saccades evoked or predicted at the injection site. Dorsomedial prearcuate injection sites where large saccades were elicited were classified as lFEF cases, whereas ventrolateral prearcuate sites where small saccades were evoked were designated sFEF cases. One control case was injected in the medial postarcuate area 6. We found five descending fiber bundles from FEF; fibers to the striatum, which enter the caudate nucleus at or just rostral to the genu of the internal capsule; fibers to the claustrum, which travel in the external capsule; and transthalamic, subthalamic, and pedunculopontine fibers. Our results indicate that transthalamic and subthalamic pathways supply all terminal sites in the thalamus, subthalamus, and tegmentum of the midbrain and pons, whereas pedunculopontine fibers appear to terminate in the pontine and reticularis tegmenti pontis nucleus exclusively. Frontal eye field terminal fields in the striatum were topographically organized: lFEF projections terminated dorsal and rostral to sFEF projections. Thus, lFEF terminal fields were located centrally in the head and body of the caudate nucleus and a small dorsomedial portion of the putamen, whereas sFEF terminal fields were located in ventrolateral parts of the caudate body and ventromedial parts of the putamen. In the claustrum, lFEF projections terminated dorsal and rostral to sFEF projections. Projections from FEF terminated in ventral and caudal parts of the subthalamic nucleus without a clear topography. By comparison, terminal fields from medial postarcuate area 6 were located more caudally and laterally in the striatum and claustrum than projections from FEF, and more centrally in the subthalamic nucleus. In the thalamus, FEF terminal patches in some thalamic nuclei were also topographically organized. Projections from lFEF terminated in dorsal area X, dorsolateral medial dorsal nucleus, pars parvicellularis (MDpc), and the caudal pole of MDpc, whereas projections from sFEF terminated in ventral area X, medial dorsal nucleus, pars multiformis, and caudal medial dorsal nucleus pars densocellularis.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of pontomedullary reticular formation stimulation on the neuronal networks responsible for rhythmical jaw movements in the guinea pig.

1. In the ketamine-anesthetized guinea pig, electromyographic (EMG) responses of the digastric muscle and vertical and horizontal movements of the mandible were studied when loci within the caudal pontine and rostral medullary reticular formation were stimulated during rhythmic jaw movements (RJMs) evoked by stimulation of the masticatory area of the cortex. 2. Within these regions electrical brain stem stimulation of the pontis nucleus caudalis and nucleus gigantocellularis (PnC-Gi) of the reticular formation completely blocked RJMs at stimulus intensities as low as 10 microA while suppressing the short-latency digastric EMG response that was time locked to each cortical stimulus in the train. PnC-Gi stimulation did not, however, reduce the excitability of the short-latency corticotrigeminal excitatory pathway to digastric motoneurons when tested by short pulse train stimulation at 2 Hz (3 pulses, 500 Hz, 0.3 ms) in the absence of RJMs. 3. Short trains (80 ms) of PnC-Gi stimuli delivered at various phases of the RJM cycle produced a permanent phase shift of the RJM rhythm. If the stimulus train was delivered at an early phase of the cycle (8-40%) the next cycle onset was advanced; if the train was delivered later in the cycle (60-80%) the next cycle onset was delayed. Long trains of PnC-Gi stimuli (100, 200, 300, and 400 ms) increased the time of onset of the next cycle by an amount directly proportional to the duration of the stimulus train. 4. Digastric EMG activity occurring during cortically evoked RJMs occupied nearly 50% of the cycle. If a short train of PnC-Gi stimuli was delivered between approximately 5 and 125 ms after the onset of the burst, the duration of the burst was significantly shortened. 5. These results demonstrate that the suppression of cortically evoked RJMs resulting from PnC-Gi stimulation is due to direct effects on central circuits responsible for the production of the RJM behavior and not on the motoneurons themselves. The evidence presented is consistent with our previously presented hypothesis that the neurons involved in mediating the short-latency corticotrigeminal pathway to digastric motoneurons are separate and distinct from those neurons comprising the central networks responsible for the production of the fundamental jaw oscillation during RJMs.

The efferent projections of the rat lateral habenular nucleus revealed by the PHA-L anterograde tracing method

The efferent connections of the rat lateral habenular nucleus (LHb) were demonstrated using anterograde transport of the lectin Phaseolus vulgaris leucoagglutinin (PHA-L). Following PHA-L injections into the LHb, neuronal somata located in the lateral two thirds of the LHb were labeled with PHA-L. Individual axonal fibers and terminal specializations were clearly visible. This permitted detailed mapping of both efferent fiber pathways and terminal distributions. Previous reports on fiber pathways were substantially confirmed and several new findings were revealed. (1) Major rostrally oriented fibers enter the medial forebrain bundle via 3 routes which initially branch from the fasciculus retroflexus: the mediodorsal thalamic nucleus and ventromedial thalamic nucleus; the zona incerta and fields of Forel; and the ventral tegmental area of Tsai. (2) A major decussation to the contralateral thalamic nuclei occurs in the central medial thalamic nucleus. (3) Caudally directed fibers follow two courses: one to the deep mesencephalic nucleus, central grey, dorsal raphe nucleus and the deep layers of the superior colliculus; and the other to the median raphe nucleus, oral pontine reticular formation and raphe pontis nucleus. The present results offer more detailed information concerning the dorsal diencephalic system.

Chapter 33 Mechanisms of vestibular compensation in the unilateral labyrinthectomized cat

The autoradiographic [14C]deoxyglucosem ethod for quantitative determination of LCGU was used to study the compensatory process following hemilabyrinthectomy in adult cats. In the critical stage when the cats were not compensated, glucose utilization in the deafferented vestibular nuclei was well below that of the intact side. The increased LCGU was seen in nucleus reticularis parvocellularis, nucleus pontis on both sides, ipsilateral abducens nucleus and its ventral parts. Activity levels in the inferior olive were not much changed. In the cerebellum, the posterior vermis and the nodulofloccular lobe were very active. LCGU in the cerebellar nuclei was not noticeably changed. In the compensatory stage, the rate of LCGU in the deafferented vestibular nuclei had increased to that of the intact side. The increased LCGU was evident in the nucl. reticularis parvocellularis, gigantocellularis and lateralis, and superior colliculus. Posterior vermis, nodulus and cerebellar nuclei were active. Destruction of the vermis, fastigial nuclei and surrounding white matter produced a marked imbalance during walking and a tremor of the head while the animals were feeding. These signs subsided very gradually. In addition to the above lesions, the interruption of the transreticular vestibular crossed connection produced severe motor disturbances on standing, walking and feeding. A restoration of normal functioning was not found to occur. These findings may suggest that vestibular compensation results from the combined activity of many brainstem and cerebellar structures, where intervestibular crossed pathways are seen to be one of important factors in compensation

Investigation of Central Mechanisms underlying Compensation in the Hemilabyrinthectomized Cat

The autoradiographic [14C]deoxyglucose method for quantitative determination of local cerebral glucose utilization (LCGU) was used to study the compensatory process following hemilabyrinthectomy in adult cats. In the critical stage when the cats were uncompensated, LCGU in the deafferented vestibular nuclei was well below that of the intact side. Increased LCGU was seen in contralateral nucleus reticularis parvocellularis, the bilateral nuclei pontis, and the ipsilateral abducens nucleus and its ventral parts. Activity levels in the inferior olive were essentially unchanged. In the cerebellum, the posterior vermis and the nodulofloccular lobe were very active. LCGU in the cerebellar nuclei was not noticeably changed. In the compensatory stage, the rate of LCGU in the deafferented vestibular nuclei had increased to that of the intact side. The increased LCGU was bilaterally evident in the nuclei reticularis parvocellularis, gigantocellularis, and lateralis, and superior colliculus. The posterior vermis, nodulus, and cerebellar nuclei were active. Destruction of the vermis, fastigial nuclei, and surrounding white matter produced marked imbalance during walking and a tremor of the head during feeding. These signs subsided very gradually. Interruption of the transreticular vestibular crossed connection produced severe motor disturbances on standing, walking, and feeding, and normal function was not restored. These findings suggest that vestibular compensation results from the combined activity of many brainstem and cerebellar structures, where intervestibular crossed pathways are considered an important factor in compensation.

Topographic localization of neuromedin u-like structures in the rat brain: An immunohistochemical study

The distribution of neuromedin Us, uterus-stimulating and hypertensive peptides newly identified in porcine spinal cord, was examined in the rat brain by the indirect immunofluorescent method. Neuromedin U-like immunoreactive structures were found to be unevenly distributed in the neuronal system. Neuromedin U-like immunoreactive neurons were present in the cranial motor nuclei, reticular nuclei, nucleus vestibularis lateralis, trigeminal sensory nuclei, colliculus superior and inferior, lemniscus lateralis, nucleus pontis, nucleus ruber, zona incerta, substantia innominata, horizontal limb of the diagonal band and cerebral cortex. The immunoreactive fibres were found in the above areas, particularly near the labelled cells, forming a fibre plexus with various intensities of immunoreactivity. In addition, dense plexuses were also seen in the nucleus reticularis thalami, nucleus ventralis posteromedialis, nucleus ventralis posterolateralis, nucleus tegmentalis dorsalis and ventralis, vertical limb of the diagonal band, nucleus olivaris superior, and nucleus pontis. In the first six structures, no labelled neurons were present and in the remaining structures, a few scattered neurons were noted. This indicates that these fibres are probably of extrinsic origin.

Neuronal activity in nuclei pontis and reticularis tegmenti pontis related to forelimb movements of the monkey

The activity of the pontine nucleus (PN) neuron was recorded in 3 monkeys moving a handle alternately from start to target zones in a simple extension-flexion movement at the wrist. Of 73 PN neurons related to the task, 44 were related to movement, 19 to handle holding and 5 to both movement and holding of the handle. Of the 44 movement-related neurons, 16 were related to flexion, 22 to extension, and 6 to both. In 37 of 54 analyzed movements of the PN neurons which were related to movements, or to both movements and handle holding, the change of the activity occurred before the movement. However, in most of these cases ( 24 37 ), discharge occurred less than 100 ms earlier than the start of the movement. In the remaining one-third of movements ( 17 54 ), neurons discharged after the onset of the movement. Locations of the 73 neurons were histologically verified in the pontine nucleus. Somewhat similar observations were made of 14 cells located in the nucleus reticularis tegmenti pontis (NRTP). Considering that the majority of movement-related PN and NRTP neurons discharged immediately before or even after the onset of movement, these neurons may play a role in the execution of movement, at least of a simple movement, rather than in the initiation or planning of movement.

The nuclei of origin of brainstem enkephalin and cholecystokinin projections to the spinal trigeminal nucleus of the rat

The sites of origin of brain stem enkephalin and cholecystokinin projections to the rodent spinal trigeminal nucleus were studied utilizing the combined retrograde transport-peroxidase antiperoxidase immunohistochemical technique. Several brain stem areas were found to contain enkephalin- like immunoreactive double-labeled neurons following injection of wheat germ agglutinin-horseradish peroxidase or horseradish peroxidase into the spinal trigeminal nucleus. The largest numbers of enkephalin doubled-labeled neurons were identified in the nucleus pontis oralis, nucleus raphe obscurus, nucleus raphe medianis, medial vestibular nucleus and the midbrain periaqueductal gray. Enkephalin projections to the spinal trigeminal nucleus were also found to originate from the nucleus solitarius, nucleus raphe pallidus, nucleus raphe magnus, nucleus raphe dorsalis, nucleus reticularis paragigantocellularis, nucleus reticularis gigantocellularis pars alpha and the deep mesencephalic nucleus. In contrast to the numerous sources of enkephalin input to the spinal trigeminal nucleus, cholecystokinin projections to this region were limited to four brain stem nuclei. These included the nucleus solitarius, raphe obscurus, nucleus paragigantocellularis and the ventral reticular nucleus of the medulla. The finding that only a small number of brain stem cholecystokinin-like immunoreactive neurons project to the spinal trigeminal nucleus supports the hypothesis that most of the cholecystokinin input to the spinal trigeminal nucleus arises from primary afferent trigeminal fibers. The spinal trigeminal nucleus is known to play a role in processing sensory information and in the transmission of orofacial nociception. The present study identifies several brain stem sites which provide enkephalin and/or cholecystokinin input to the spinal trigeminal nucleus. Several of these nuclei have been implicated as components of the endogenous pain control system and the present results raise the possibility that they may modulate incoming orofacial nociception by releasing the endogenous opioid, enkephalin. Cholecystokinin, on the other hand, has been demonstrated in other studies to attenuate the action of opiates and thus may play an opposing role in the spinal trigeminal nucleus.

Subcortical Afferents to the Nucleus Reticularis Tegmenti Pontis in the Rabbit: A Retrograde Horseradish Peroxidase Study

Summary: The subcortical afferent projections to the nucleus reticularis tegmenti pontis (RT)were identified from the retrograde transport of horseradish peroxidase (HRP). HRP was injected into the medial and lateral parts of the RT, respectively. The major afferent inputs to the RT were found to arise ipsilaterally from the nucleus of the fields of Forel, the medial division of the medial mammillary nucleus, the region lateral to the red nucleus, and the posterior commissural nucleus; contralaterally from the anterior pretectal nucleus, the deep layer of the superior colliculus, and the supragenual nucleus; and bilaterally from the lateral habenular nucleus, the retrorubral nucleus, the central and posterior nuclei of the interpeduncular complex, the gray matter along the floor of the fourth ventricle, and the prepositus hypoglossi nucleus. Regions containing fewer labeled cells included the premammillary nucleus, the zona incerta, the nucleus pontis centralis oralis and the medial vestibular nucleus. In addition, the medial division of the medial mammillary nucleus, the lateral habenular nucleus, the central and posterior nuclei of the interpeduncular complex, and the supragenual nucleus were found to project mainly to the medial part of the RT. The superior colliculus, the retrorubral nucleus and the gray matter along the floor of the fourth ventricle projected mainly to the lateral part of the RT.These results indicate that the medial part of the RT receives fibers mainly from the diencephalic limbic areas, whereas the lateral part of the RT receives fibers mainly from nonlimbic (somatomotor, visuomotor and vestibular) areas.

Sleep in the cat: raphe dorsalis and vasotocin.

To determine the relationship between the raphe nuclei and the sleep-inducing pineal peptide arginine vasotocin (AVT), we investigated the hypnogenic effects of intraventricularly administered AVT in adult cats with electrolytic lesions performed either in the raphe dorsalis nucleus (RDN) or the raphe pontis nucleus (RPN). The following results were observed: (a) RDN lesions produced a quantitative decrease in NREM sleep and a transitory increase in REM sleep and narcoleptic-like alterations of REM sleep in the first 2-5 postoperative days. On the eighth postoperative day, normal (prelesion) sleep parameters were restored. (b) RDN lesions prevented AVT from inducing its hypnogenic effects during the first 5 postoperative days, but the AVT hypnogenic effects reappeared when sleep parameters reached prelesion levels. (c) Although the RPN lesions produced a slight but statistically significant REM sleep decrease, this did not prevent AVT from inducing its hypnogenic effects. We conclude that (a) the anatomic site of AVT action within the brain may be related to RDN; (b) at least some of the sleep disturbances observed after RDN lesions (narcolepsy) may be due to damage of the AVT site of action or to modifications of AVT synthesis or release; (c) RDN belongs to a large neural circuit that includes the pineal gland and habenula, a circuit that may play an important role in the sleep-wake cycle by "fine-tuning" sleep mechanisms. We hypothesize that AVT could be the specific inhibitory neuromodulator of this neural circuit.

Fastigial nucleus projections to the brain stem in beagles: Pathways for autonomic regulation

Efferent connections from a portion of the cerebellar fastigial nucleus were investigated using autoradiography. Bipolar stimulating electrodes were placed in the fastigial nucleus of anesthetized beagles and the area that produced increases in blood pressure and heart rate was localized. A mixture of [ 3H]leucine and [ 3H]proline (4:1) was injected into the area and autoradiograms of transported material were prepared. Injections filled the rostral and various parts of the caudal fastigial nucleus. Labeled axons reached the brain stem via two routes, the ipsilateral juxtarestiform body and the contralateral uncinate fasciculus. Ventral portions of the lateral vestibular nucleus were labeled bilaterally, projections to the inferior vestibular and medial vestibular nuclei are contralateral. Nucleus tractus solitarius was heavily labeled on the side opposite the injection. The contralateral medial reticular formation contained many labeled terminals and axons. Label was found in the nucleus reticularis ventralis, lateral reticular nucleus, nucleus gigantocellularis, nucleus pontis caudalis and the paramedian reticular nucleus. No terminal labeling was found in nucleus parvocellularis or nucleus ambiguus. Stimulation of the rostral fastigial nucleus produces increases in blood pressure and heart rate by generalized sympathoexcitation. Many cell groups which facilitate the activity of preganglionic sympathetic neurons do not receive direct fastigial input. It is suggested that sympathoexcitation resulting from stimulation of the fastigial nucleus occurs through multisynaptic connections in the brain stem.

The afferent and efferent connections of the feline nucleus tegmenti pedunculopontinus, pars compacta.

AbstractThe fiber connections of the nucleus tegmenti pedunculopontinus, pars compacta (TPc) were studied by means of the anterograde autoradiographic and retrograde horseradish peroxidase tracer methods. The limits of TPc, which is not a cytoarchitecturally distinct cell group in the cat, were estimated on the basis of autoradiographic experiments in which we plotted the distribution of afferent connections from the entopeduncular nucleus, motor cortex, substantia nigra, and subthalamic nucleus. We concluded that in the cat, TPc can most readily be identified by the terminal distribution of fibers originating in the substantia nigra. Deposits of radiolabel in the motor‐pre‐motor cortex, the entopeduncular nucleus, and subthalamic nucleus weakly labeled the same tegmental region. Parallel horseradish peroxidase experiments suggested that neurons near the entopeduncular nucleus, especially in the lateral hypothalamus and subthalamus, contribute to the pallido‐TPc pathway; that entopeduncular neurons projecting to TPc are most numerous in the ventral part of the nucleus; and that of the neocortical motor fields, both areas 4 and 6 project to TPc.An autoradiographic study of the efferent connections of TPc showed that the major connections were directed toward more rostral structures. Small deposits of labeled amino acids centered in TPc invariably elicited bilateral labeling of the pars compacta of the substantia nigra and the subthalamic nucleus, the densest label being on the ipsilateral side. Other structures variably or more sparsely labeled were: the posterior and lateral hypothalamus; centre median complex; an intermediate part of the lateral thalamic nucleus; central gray substance; nucleus parabrachialis pigmentosus (retro‐rubral nucleus); the raphe nuclei linearis intermedius, dorsalis, and magnus; nucleus reticularis tegmenti pontis; the pontine and medullary reticular for‐mation including the nuclei pontis oralis and caudalis; and the nucleus reticularis gigantocellularis, especially its ventral supraolivary part. These observations demonstrate that TPc shares some connections with a wider tegmental region, but that, in addition, TPc is characterized by a set of afferent and efferent connections that differentiate it from the surrounding teg‐mentum and affiliate it with the basal ganglia. By comparison with findings in the monkey and rat, these experiments further suggest that the connections of TPc may vary across mammalian species. The location and fiber connections of TPc indicate that it is probably distinct from the physiologically defined mesencephalic locomotor region, but suggest the hypothesis that TPc, as a part of an extrapyramidal tegmental loop‐circuit, may be involved in the production of simple resting tremors.

Retrograde HRP identification of neurons in the rhombencephalon and spinal cord of the rat that project to the dorsal mesencephalon.

Neurons in the rhombencephalon and spinal cord of the rat that project to the dorsal midbrain were identified using the HRP retrograde neuroanatomical tracing method. Retrogradely labeled neurons were most numerous in the reticular formation, specifically in nucleus pontis oralis, caudalis, and gigantocellularis and in the sensory trigeminal complex. Neurons that project were also found in certain raphe nuclei, the parabrachial nuclei, the deep cerebellar nuclei, the vestibular cochlear complex, and the spinal cord. The diverse distribution of neurons that project to the midbrain is understandable in the context of the known diverse functions of the region, which include a role in sexual and other behaviors, nociception, and various autonomic functions.

Brainstem projections to the normal and noradrenergically hyperinnervated trigeminal motor nucleus.

The noradrenergic innervation of the trigeminal motor nucleus of the rat can be increased severalfold by neonatal treatment with the neurotoxin, 6-hydroxydopamine. The brainstem projections to the nucleus were studied by injecting HRP into the nucleus of normal and noradrenergically hyperinnervated rats. In order to identify the source of the noradrenergic innervation, the fluorescent dye, True Blue, was used as a retrograde tracer in combination with the glyoxylic acid histofluorescence method for catecholamines. In both control and neonatally treated rats, the noradrenergic innervation of the motor nucleus was shown to arise from an ipsilateral group of cells located among the fibers of the lateral lemniscus just rostral to the motor nucleus. Our results confirmed the high degree of specificity of noradrenergic innervation, which arises exclusively from this lateral tegmental noradrenergic cell group. During the process of sprouting, this specificity is maintained since only those noradrenergic cells normally innervating the nucleus were retrogradely labeled in neonatally treated animals. Other noradrenergic projections which are also increased in these animals, such as the nearby locus ceruleus innervation of the main sensory trigeminal nucleus, do not spread to the motor trigeminal nucleus. HRP-labeled nonadrenergic cells were concentrated dorsally, with scattered cells surrounding the nucleus. A similar distribution was observed contralateral to the injection site. The mesencephalic trigeminal nucleus was labeled only ipsilateral to the injection. The motor nucleus also receives an extensive bilateral input from the pontine and medullary reticular formation. The medial reticular formation nuclei, including nucleus pontis caudalis, nucleus gigantocellularis, and nucleus reticularis ventralis contained large labeled cells, which were especially numerous in the retrotrigeminal area. Smaller, lateral reticular formation neurons were concentrated rostrally and ipsilaterally in the nucleus pontis lateralis. HRP retrograde labeling revealed no obvious change in the overall pattern of cells innervating the trigeminal motor nucleus following noradrenergic hyperinnervation.

Synaptic Mechanisms and Circuitry Involved in Motoneuron Control During Sleep

Spontaneous amplitude fluctuations of the brainstem monosynaptic trigeminal jaw-closing reflex were examined in the freely moving chronic cat during wakefulness, quiet sleep, and active sleep. The largest amplitude responses occurred during active wakefulness; they decreased in size during quiet sleep. The lowest amplitude responses occurred during active sleep. A chronic cat preparation was developed in order to record intracellularly from identified trigeminal motoneurons for prolonged period of time throughout the states of sleep and wakefulness. The membrane potential of trigeminal motoneurons exhibited fluctuations that were correlated with changes in the animal's behavioral state. The fundamental pattern consisted of (a) slight hyperpolarization during quiet sleep, compared to arousal or alert wakefulness, (b) little if any hyperpolarization during quiet sleep compared to quiet wakefulness, and (c) dramatic hyperpolarization when active sleep was compared to quiet sleep. Sustained spike activity of trigeminal motoneurons, when present during wakefulness, decreased in frequency or tended to occur in bursts when the animal was in quiet sleep. During active sleep, activity ceased except for a few isolated spikes or short-duration bursts of action potentials. Based on an analysis of antidromically induced spike potentials and monosynaptically induced postsynaptic potentials, it was concluded that postsynaptic inhibition of trigeminal motoneurons during active sleep acts to suppress somatic reflex activity and produce muscular atonia. A companion study of the membrane potential of lumbar motoneurons in the chronic, unanesthetized, undrugged, normally respiring cat was performed during sleep and wakefulness. The antidromic field potential, antidromic and orthodromic spike, EPSP, membrane input resistance, and rheobasic current of lumbar motoneurons were studied during sleep and wakefulness. No change in motoneuron excitability occurred when quiet wakefulness was compared to quiet sleep. Postsynaptic inhibition resulted in decrease in excitability during active sleep. Further phasic decreases in excitability, also due to postsynaptic inhibition, occurred during active sleep in conjunction with clusters of rapid eye movements. The mesencephalon, pons, and medulla were explored in a conditioning-test paradigm in an attempt to find a site where electrical stimulation induced a pattern of somatomotor reflex and motoneuron membrane potential modulation comparable to that which occurs spontaneously during sleep and wakefulness. In unanesthetized, freely moving cats during wakefulness and quiet sleep, electrical stimulation within and in the vicinity of the nucleus pontis oralis produced facilitation of the masseteric reflex, whereas during active sleep the identical stimulus resulted in potent suppression of the reflex.(ABSTRACT TRUNCATED AT 400 WORDS)

The nuclei of origin of brain stem enkephalin and substance P projections to the rodent nucleus raphe magnus

The sites of origin of brain stem enkephalin and substance P projections to the rodent nucleus raphe magnus were studied utilizing the combined horseradish peroxidase retrograde transport-peroxidase-antiperoxidase immunohistochemical technique. Several brain stem areas were found to contain both enkephalin- and substance P-like immunoreactive double labeled neurons following injection of horseradish peroxidase into the raphe magnus. Nuclei providing both enkephalin and substance P inputs to the raphe magnus include the nucleus reticularis paragigantocellularis, the nucleus cuneiformis, the nucleus solitarius and the trigeminal subdivision of the lateral reticular nucleus. Enkephalin projections to the raphe magnus were also found to originate from the dorsal parabrachial nucleus, the nucleus reticularis gigantocellularis pars α and from an area which corresponds to the A5 group of Dahlström & Fuxe. Additional neurons containing substance P-like immunoreactivity and horseradish peroxidase reaction product were identified in the superior central raphe nucleus and the nucleus pontis oralis. The midbrain periaqueductal gray contributes very few enkephalin and substance P fibers to the raphe magnus. The nucleus raphe magnus is a key structure in the intrinsic analgesia system and it has also been implicated in other diverse and non-nonciceptive functions. The present study identifies several brain stem sites which provide enkephalin and substance P input to this raphe nucleus. Several of these nuclei have been implicated in central analgesic mechanisms or in non-nociceptive autonomic functions. The present investigation raises the possibility that these brain stem regions may modulate neuronal activity in the raphe magnus via enkephalin or substance P projections and thus influence the involvement of the raphe magnus in both opiate related mechanisms of pain control and non-nociceptive functions.

Corticofugal influences on pontine unit activity

Unit responses of the nuclei pontis (NP) and reticular pontine nuclei (RPN) to stimulation of the frontobasal cortex (proreal, orbital, and basal temporal regions) and of the dorsal hippocampus were studied in cats. Stimulation of the various cortical structures was found to induce phasic and (less frequently) tonic responses in neurons of NP and RPN. The main type of unit response in RPN was primary excitation, whereas in NP it was primary inhibition. The largest number of responding neurons in the pontine nuclei was observed to stimulation of the proreal gyrus. In the cerebro-cerebellar relay system neurons of the reticular tegmental nucleus and ventromedial portion of NP showed the highest ability to respond. In the oral and caudal reticular pontine nuclei the regions of predominant influence of cortical structures were located in zones of these nuclei where neurons with rostral and (to a lesser degree) caudal projections were situated.

Intracellular potential of medullary reticular neurons during sleep and wakefulness

Intracellular records were obtained in the chronic cat from neurons of the nucleus reticularis gigantocellularis (NGC) during naturally occurring sleep and wakefulness. When wakefulness and quiet sleep was compared with active sleep, the membrane potential level of NGC neurons gradually decreased; a depolarized membrane potential was maintained tonically and selectively throughout active sleep. These data support the concept that NGC neurons assist in the generation of somatic atonia during active sleep and suggest that this state-dependent inhibitory function may be controlled by the nucleus pontis oralis as part of the general phenomenon of reticular response reversal.