Lateral Medullary Reticular Formation Research Articles

Organization of Functional Synaptic Connections between Medullary Reticulospinal Neurons and Lumbar Descending Commissural Interneurons in the Neonatal Mouse

The medullary reticular formation (MRF) of the neonatal mouse is organized so that the medial and lateral MRF activate hindlimb and trunk motoneurons (MNs) with differential predominance. The goal of the present study was to investigate whether this activation is polysynaptic and mediated by commissural interneurons with descending axons (dCINs) in the lumbar spinal cord. To this end, we tested the polysynapticity of inputs from the MRF to MNs and tested for the presence of selective inputs from medial and lateral MRF to 574 individual dCINs in the L2 segment of the neonatal mouse. Reticulospinal-mediated postsynaptic Ca(2+) responses in MNs were reduced in the presence of mephenesin and after a midline lesion, suggesting the involvement of dCINs in mediating the responses. Consistent with this, stimulation of reticulospinal neurons in the medial or lateral MRF activated 51% and 57% of ipsilateral dCINs examined (255 and 352 dCINs, respectively) and 52% and 46% of contralateral dCINs examined (166 and 133 dCINs, respectively). The proportion of dCINs that responded specifically to stimulation of medial or lateral MRF was similar to the proportions of dCINs that responded to both MRF regions or to neither. The three responsive dCIN populations had largely overlapping spatial distributions. We demonstrate the existence of dCIN subpopulations sufficient to mediate responses in lumbar motoneurons from reticulospinal pathways originating from the medial and lateral MRF. Differential control of trunk and hindlimb muscles by the medullary reticulospinal system may therefore be mediated in part by identifiable dCIN populations.

Neural circuits controlling diaphragm function in the cat revealed by transneuronal tracing

Although a number of studies have considered the neural circuitry that regulates diaphragm activity, these pathways have not been adequately discerned, particularly in animals such as cats that utilize the respiratory muscles during a variety of different behaviors and movements. The present study employed the retrograde transneuronal transport of rabies virus to identify the extended neural pathways that control diaphragm function in felines. In all animals deemed to have successful rabies virus injections into the diaphragm, large, presumed motoneurons were infected in the C(4)-C(6) spinal segments. In addition, smaller presumed interneurons were labeled bilaterally throughout the cervical and upper thoracic spinal cord. While in short and intermediate survival cases, infected interneurons were concentrated in the vicinity of phrenic motoneurons, in late survival cases, the distribution of labeling was more expansive. Within the brain stem, the earliest infected neurons included those located in the classically defined pontine and medullary respiratory groups, the medial and lateral medullary reticular formation, the region immediately ventral to the spinal trigeminal nucleus, raphe pallidus and obscurus, and the vestibular nuclei. At longer survival times, infection appeared in the midbrain, which was concentrated in the lateral portion of the periaqueductal gray, the region of the tegmentum that contains the locomotion center, and the red nucleus. Considerable labeling was also present in the fastigial nucleus of the cerebellum, portions of the posterior and lateral hypothalamus and the adjacent fields of Forel known to contain hypocretin-containing neurons and the precruciate gyrus of cerebral cortex. These data raise the possibility that several parallel pathways participate in regulating the activity of the feline diaphragm, which underscores the multifunctional nature of the respiratory muscles in this species.

Differential origin of reticulospinal drive to motoneurons innervating trunk and hindlimb muscles in the mouse revealed by optical recording

To better understand how the brainstem reticular formation controls and coordinates trunk and hindlimb muscle activity, we used optical recording to characterize the functional connections between medullary reticulospinal neurons and lumbar motoneurons of the L2 segment in the neonatal mouse. In an isolated brainstem-spinal cord preparation, synaptically induced calcium transients were visualized in individual MNs of the ipsilateral and contralateral medial and lateral motor columns (MMC, LMC) following focal electrical stimulation of the medullary reticular formation (MRF). Stimulation of the MRF elicited differential responses in MMC and LMC, according to a specific spatial organization. Stimulation of the medial MRF elicited responses predominantly in the LMC whereas stimulation of the lateral MRF elicited responses predominantly in the MMC. This reciprocal response pattern was observed on both the ipsilateral and contralateral sides of the spinal cord. To ascertain whether the regions stimulated contained reticulospinal neurons, we retrogradely labelled MRF neurons with axons coursing in different spinal funiculi, and compared the distributions of the labelled neurons to the stimulation sites. We found a large number of retrogradely labelled neurons within regions of the gigantocellularis reticular nucleus (including its pars ventralis and alpha) where most stimulation sites were located. The existence of a mediolateral organization within the MRF, whereby distinct populations of reticulospinal neurons predominantly influence medial or lateral motoneurons, provides an anatomical substrate for the differential control of trunk and hindlimb muscles. Such an organization introduces flexibility in the initiation and coordination of activity in the two sets of muscles that would satisfy many of the functional requirements that arise during postural and non-postural motor control in mammals.

Intraventricular Enzyme Replacement Improves Disease Phenotypes in a Mouse Model of Late Infantile Neuronal Ceroid Lipofuscinosis

Late infantile neuronal ceroid lipofuscinosis (LINCL) is an autosomal recessive neurodegenerative disease caused by mutations in CLN2, which encodes the lysosomal protease tripeptidyl peptidase 1 (TPP1). LINCL is characterized clinically by progressive motor and cognitive decline, and premature death. Enzyme-replacement therapy (ERT) is currently available for lysosomal storage diseases affecting peripheral tissues, but has not been used in patients with central nervous system (CNS) involvement. Enzyme delivery through the cerebrospinal fluid is a potential alternative route to the CNS, but has not been studied for LINCL. In this study, we identified relevant neuropathological and behavioral hallmarks of disease in a mouse model of LINCL and correlated those findings with tissues from LINCL patients. Subsequently, we tested if intraventricular delivery of TPP1 to the LINCL mouse was efficacious. We found that infusion of recombinant human TPP1 through an intraventricular cannula led to enzyme distribution in several regions of the brain of treated mice. In vitro activity assays confirm increased TPP1 activity throughout the rostral-caudal extent of the brain. Importantly, treated mice showed attenuated neuropathology, and decreased resting tremor relative to vehicle-treated mice. This data demonstrates that intraventricular enzyme delivery to the CNS is feasible and may be of therapeutic value.

Inactivation of amino acid receptors in medullary reticular formation modulates and suppresses ingestion and rejection responses in the awake rat.

The lateral medullary reticular formation (RF) is the source of many preoromotor neurons and is essential for generation of ingestive consummatory responses. Although the neurochemistry mediating these responses is poorly understood, studies of fictive mastication suggest that both excitatory and inhibitory amino acid receptors play important roles in the generation of these ororhythmic behaviors. We tested the hypothesis that amino acid receptors modulate the expression of ingestion and rejection responses elicited by natural stimuli in awake rats. Licking responses were elicited by either intraoral (IO) gustatory stimuli or sucrose presented in a bottle. Oral rejection responses (gaping) were elicited by IO delivery of quinine hydrochloride. Bilateral microinjection of the N-methyl-D-aspartate (NMDA) receptor antagonist d-[(3)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (D-CPP) suppressed licking and gape responses recorded electromyographically from a subset of orolingual muscles. Likewise, infusion of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) significantly reduced licking and gape responses but was accompanied by spontaneous gasping responses. Rats still actively probed the bottle, indicating an intact appetitive response. Neither D-CPP nor CNQX differentially affected ingestion or rejection, suggesting that the switch from one behavior to the other does not simply rely on one glutamate receptor subtype. Nevertheless, a glutamate receptor-mediated switch from consummatory behavior to gasps after CNQX infusions suggests a multifunctional substrate for coordinating the jaw and tongue in different behaviors. Bilateral infusions of the GABA(A) receptor antagonist bicuculline or the glycine receptor antagonist strychnine enhanced the amplitude of IO stimulation-induced oral responses. These data suggest that the neural substrate underlying ingestive consummatory responses is under tonic inhibition. Release of this inhibition may be one mechanism by which aversive oral stimuli produce large-amplitude mouth openings associated with the rejection response.

Transneuronal tracing of neural pathways controlling activity of diaphragm motoneurons in the ferret

Previous studies have shown that neurons in addition to those in the medullary respiratory groups are involved in activating phrenic motoneurons during a number of behaviors, including vomiting and reaction to vestibular stimulation. However, the location of premotor inspiratory neurons outside of the main medullary respiratory groups is largely unknown, particularly in emetic species. In the present study, the transneuronal tracer pseudorabies virus was injected into the diaphragm of the ferret, and the locations of retrogradely-labeled motoneurons and transneuronally-labeled pre-motoneurons in the brainstem and cervical and thoracic spinal cord were mapped. Injections of a monosynaptic tracer, cholera toxin, were also made in order to verify the location of motoneurons innervating the diaphragm. Phrenic motoneurons identified with pseudorabies virus and cholera toxin were confined largely to the C 5–C 7 levels of spinal cord, and often gave rise to prominent polarized dendritic arbors that extended across the midline. At post-inoculation survival times ≥three days, transneuronally-labeled interneurons were located in the cervical and thoracic spinal cord and portions of the brainstem, including the midline pontomedullary reticular formation and the lateral medullary reticular formation. Double-labeling studies revealed that although the infected midline neurons were located in the proximity of serotonergic neurons, only a small number of the virus-containing cells were positive for serotonin. These findings suggest that neurons in the midline of the medulla and pons influence the activity of phrenic motoneurons, perhaps during inspiratory behaviors unique to emetic animals (such as vomiting).

Physiological basis and pharmacology of motion sickness: an update

Motion sickness can occur when sensory inputs regarding body position in space are contradictory or are different from those predicted from experience. Signals from the vestibular system are essential for triggering motion sickness. The evolutionary significance of this malady is unclear, although it may simply represent the aberrant activation of vestibuloautonomic pathways that typically subserve homeostasis. The neural pathways that produce nausea and vomiting during motion sickness are presumed to be similar to those that generate illness after ingestion of toxins. The neural substrate of nausea is unknown but may include neurons in the hypothalamus and inferior frontal gyrus of the cerebral cortex. The principal motor act of vomiting is accomplished through the simultaneous contractions of inspiratory and expiratory respiratory muscles and is mediated by neurons in the lateral medullary reticular formation and perhaps by cells near the medullary midline. Cocontraction of the diaphragm and abdominal muscles increases pressure on the stomach, which causes gastric contents to be ejected through the mouth. Effective drugs for combating motion sickness include antihistamines, antimuscarinics, 5-HT 1A (serotonergic) receptor agonists and neurokinin type 1 receptor antagonists. However, considerable information concerning the physiological basis and pharmacology of motion sickness is unknown; future research using animal models will be required to understand this condition.

Integration of somatic and visceral inputs by the brainstem: functional considerations.

Studies of the brainstem have traditionally either focused on mechanisms for the control of limb or axial muscles or for the maintenance of homeostasis (e.g., the circuitry for the regulation of respiration or blood pressure). However, recent studies have demonstrated that movement and changes in cardiorespiratory activity often are coordinated, indicating a linkage between the pathways that control somatic motor activity and those that regulate respiration or circulation. Neurons in regions such as nucleus tractus solitarius and the lateral medullary reticular formation that regulate circulation and respiration have been shown to receive somatic sensory signals (including those from the vestibular system) indicating body position in space. In addition, somatic motor control may be influenced by signals from visceral receptors that provide cues regarding body position in space. Some areas of the brainstem may also participate directly in both motor control and regulation of blood pressure and respiration. Thus, a simple division of the brainstem into "somatic" and "autonomic" regions is no longer possible.

Connections of the caudal ventrolateral medullary reticular formation in the cat brainstem.

A region of the caudal ventrolateral medullary reticular formation (CVLM) participates in baroreceptor, vestibulosympathetic, and somatosympathetic reflexes; the adjacent retroambigual area is involved in generating respiratory-related activity and is essential for control of the upper airway during vocalization. However, little is known about the connections of the CVLM in the cat. In order to determine the locations of terminations of CVLM neurons, the anterograde tracers Phaseolus vulgaris leucoagglutinin and tetramethylrhodamine dextran amine were injected into this region. These injections produced a dense concentration of labeled axons throughout the lateral medullary reticular formation (lateral tegmental field), including the retrofacial nucleus and nucleus ambiguus, regions of the rostral ventrolateral medulla, the lateral and ventrolateral aspects of the hypoglossal nucleus, nucleus intercalatus, and the facial nucleus. A smaller number of labeled axons were located in the medial, lateral, and commissural subnuclei of nucleus tractus solitarius, the A5 region of the pontine reticular formation, the ventral and medial portions of the spinal and motor trigeminal nuclei, locus coeruleus, and the parabrachial nucleus. We confirmed the projection from the CVLM to both the rostral ventrolateral medulla and lateral tegmental field using retrograde tracing. Injections of biotinylated dextran amine or Fluorogold into these regions resulted in retrogradely labeled cell bodies in the CVLM. However, the neurons projecting to the lateral tegmental field were located mainly dorsal to those projecting to the rostral ventrolateral medulla, suggesting that these neurons form two groups, possibly with different inputs. Injections of retrograde tracers into the lateral tegmental field and rostral ventrolateral medulla also produced labeled cell bodies in other regions, including the medial and inferior vestibular nuclei and nucleus solitarius. These data are consistent with the view that the CVLM of the cat is a multifunctional area that regulates blood pressure, produces vocalization, affects the shape of the oral cavity, and elicits contraction of particular facial muscles.

Processing of vestibular and other inputs by the caudal ventrolateral medullary reticular formation.

Lesions of the lateral medullary reticular formation caudal to the obex abolish vestibulosympathetic and somatosympathetic responses; this area also contains neurons that mediate baroreceptor reflexes. Recordings were made from neurons in the caudal medullary reticular formation of cats that were decerebrate or anesthetized using alpha-chloralose-urethan to determine whether common neurons responded to electrical stimulation of vestibular and hindlimb afferents and had cardiac-related (i.e., baroreceptor) inputs. Many neurons in the ventrolateral portion of the caudal reticular formation received labyrinthine inputs, and they were interspersed with neurons that received baroreceptor signals. However, virtually none of the units received convergent baroreceptor and vestibular inputs, suggesting that separate pathways from the caudal ventrolateral medulla mediate baroreceptor and vestibulosympathetic reflexes. Furthermore, the neurons that received labyrinthine signals could not be antidromically activated from electrodes inserted into the rostral ventrolateral medulla, which is known to mediate vestibulosympathetic responses; thus an indirect pathway must convey vestibular inputs from the caudal to rostral medullary reticular formation. Over 75% of both neurons with baroreceptor inputs and cells with vestibular signals responded to sciatic nerve stimulation, suggesting that more than one pathway from the caudal medulla may mediate somatosympathetic responses.

Study on Vomiting Related to the Vestibulo-Autonomic Reflex

The purpose of this study was to investigate the neural pathway from the vestibular labyrinth to the medullary vomiting center in the cat, using electrophysiological techniques. During electrical stimulation of the canal nerve, we found conflicting results: the pressure in the stomach sometimes increased, and sometimes decreased. There might be several neural structures between the semicircular canal nerve and the vomiting center in the dorsolateral portion of the reticular formation of medulla oblongata. Retching or vomiting-like behavior during both respiration and movement of the stomach was recorded during stimulation at several sites in the lateral medullary reticular formation. However, the evoked unit activities were not always induced by stimulation of the canal nerve.

Distribution of alpha 1 adrenoceptors in rat brain revealed by in situ hybridization experiments utilizing subtype-specific probes

The distribution of neurons in the rat CNS that synthesize mRNA for the alpha 1A/D and alpha 1B adrenoceptors was revealed by the in situ hybridization method. Forty-eight-mer DNA probes were synthesized to two different and unique regions of both the alpha 1A/D and alpha 1B mRNAs. Tissue sections from all levels of the CNS and some peripheral ganglia were incubated in a hybridization cocktail containing one of these four probes. The two mRNAs were expressed in a discrete and often complementary manner to each other, and identical hybridization patterns were seen for the probes directed against the same mRNA. The alpha 1A/D probes hybridized heavily with neurons in the internal granular and internal plexiform layers of the olfactory bulb, in layers II-V of most areas of the cerebral cortex, and in the lateral aspect of the lateral amygdaloid nucleus, with pyramidal neurons of CA1-CA4 regions, hilar and granular neurons of the dentate gyrus, and neurons in the reticular thalamic nucleus, cranial and spinal motor nuclei, and the inferior olivary nucleus. Light labeling was seen in a variety of other regions in the brain and spinal cord. The alpha 1B probes hybridized heavily with neurons in the mid layers of cerebral cortex and with virtually all neurons in the thalamus, except the reticular and habenular nuclei. In addition, labeling was seen in the lateral and central amygdaloid nuclei, in brainstem and spinal motor nuclei, over most neurons of the dorsal and medullary raphe nuclei and neurons of the intermediolateral cell column in the spinal cord. Light labeling was seen in the septal nucleus, the horizontal limb of the diagonal band, the paraventricular and lateral hypothalamic nuclei, the pontine and medullary reticular formation, and in most laminae in the spinal cord. The patterns of labeling obtained with the alpha 1B probes resemble the labeling seen in previous autoradiographic ligand binding studies utilizing "general" alpha 1 ligands, while the labeling patterns seen with the alpha 1A/D probes do not correspond to any published alpha 1 receptor distribution pattern, indicating that this mRNA likely encodes for a novel adrenoceptor. The present findings further expand the heterogeneity of adrenoceptor mRNAs presented in two accompanying studies (Nicholas et al., 1993a,b). This differential distribution of adrenoceptors subtypes provides a framework for the functional diversity to the apparently widespread, diffuse, and rather homogeneous noradrenergic innervation of the CNS.

Afferents to the nucleus reticularis parvicellularis of the cat medulla oblongata: a tract-tracing study with cholera toxin B subunit.

The aim of this study was to examine anatomical evidence in cats of whether the nucleus reticularis parvicellularis (Pc) is part of the circuit responsible for the inhibition of brainstem motoneurons during paradoxical sleep. For this purpose, we made iontophoretic injections of the retrograde and anterograde tracer cholera toxin B subunit (CTb) in the Pc. After CTb injections in the Pc, a large number of retrogradely labeled neurons were seen in the central nucleus of the amygdala, the lateral part of the bed nucleus of the stria terminalis, the posterior hypothalamic areas, the mesencephalic reticular formation, the nucleus locus subcoeruleus, the nucleus pontis caudalis, other portions of the Pc, the nucleus reticularis dorsalis, the trigeminal sensory complex, and the nucleus of the solitary tract. We further found that the Pc receives 1) serotoninergic afferents from the raphe dorsalis, magnus, and obscurus nuclei; 2) noradrenergic inputs from the dorsolateral pontine tegmentum; 3) cholinergic afferents from the lateral medullary reticular formation; 4) substance P-like afferents from the central nucleus of the amygdala, bed nucleus of the stria terminalis, periaqueductal gray, and nucleus of the solitary tract; and 5) methionine-enkephalin-like projections from the periaqueductal gray, the nucleus of the solitary tract, the lateral pontine and medullary reticular formation, and the spinal trigeminal nucleus. We further found that the Pc do not receive afferents from brainstem structures responsible for muscle atonia, such as the ventromedial medulla and the dorsomedial pontine tegmentum, and therefore may not be part of the circuit inhibiting the brainstem motoneurons during paradoxical sleep.

Connections between hypothalamus and medullary reticular formation mediate coronary vasoconstriction

We have recently identified discrete sites within the lateral hypothalamus and medullary reticular formation that, when stimulated electrically, produce neurally mediated coronary vasoconstriction. This study examined whether these sites are part of the same coronary vasomotor pathway. The neuronal tracing dye fast blue was injected in cats into the coronary vasoconstrictor site within medullary reticular formation. Fluorescence microscopy revealed major afferent projections originating from within the same region of midbrain ventrolateral periaqueductal gray that receives projections from lateral hypothalamus. To determine the functional importance of the proposed connections between the hypothalamic and medullary sites, anesthetized cats were prepared for continuous hemodynamic measurements. Constant current electrical stimulation within lateral hypothalamus produced significant increases in heart rate (21 +/- 6%), arterial pressure (11 +/- 3%), and femoral (36 +/- 18%) and coronary resistances (14 +/- 9%) with no change in coronary flow velocity (-1.1 +/- 2.5%). After beta-adrenoreceptor blockade, significantly greater increases in arterial pressure (35 +/- 8%) and coronary resistance (39 +/- 5%) with transient decreases in coronary flow velocity (21 +/- 6%) were seen. Microinjections of lidocaine into the medullary site blocked coronary constriction produced by lateral hypothalamic stimulation (39 +/- 5% increase in coronary resistance to electrical stimulation before and 2.4 +/- 2% increase after lidocaine in medullary reticular formation). These data provide evidence that specific regions of lateral hypothalamus and medullary reticular formation are part of a common central vasomotor projection that mediates coronary vasoconstriction in addition to other hemodynamic effects.

Immunohistochemical study of choline acetyltransferase‐immunoreactive processes and cells innervating the pontomedullary reticular formation in the rat

The present study was undertaken to examine the cholinergic innervation of the brainstem reticular formation in an effort to understand the potential role of cholinergic neurons in processes of sensory-motor modulation and state control. The cholinergic cells and processes within the pontomedullary reticular formation were studied in the rat by application of peroxidase-antiperoxidase immunohistochemistry with silver intensification for choline-acetyltransferase (ChAT). ChAT-immunoreactive cells were located in the pontomesencephalic tegmentum within the laterodorsal and pedunculopontine tegmental (LDT and PPT) nuclei, where they numbered approximately 3,000 on each side and were scattered in the midline, medial, and lateral medullary reticular formation, where they numbered approximately 10,000 in total on each side. The cholinergic neurons within the reticular formation were commonly medium in size and gave rise to multiple dendrites that extended for considerable distances within the periventricular gray or the reticular formation, as is typical of other isodendritic reticular neurons. A prominent innervation of the entire pontomedullary reticular formation was evident by varicose ChAT-immunoreactive fibers that often surrounded large noncholinergic reticular neurons in a typical perisomatic pattern of termination, suggesting a potent influence of the cholinergic innervation on pontomedullary reticular neurons. The contribution of the pontomesencephalic cholinergic neurons to the innervation of the medial medullary and lateral pontine reticular formation was studied by retrograde transport of horseradish peroxidase conjugated wheat germ agglutinin (WGA-HRP) in combination with ChAT immunohistochemistry. A proportion of the cholinergic neurons within the laterodorsal tegmental nucleus (pars alpha) and the pedunculopontine tegmental nucleus were retrogradely labelled on the ipsilateral (10-15%) and contralateral (5-10%) sides from the medial medullary reticular formation, indicating a significant contribution to the cholinergic innervation of this region, which, however, also appeared to derive in part from intrinsic medullary cholinergic neurons. The major fiber system by which the medial medullary reticular formation was reached by the pontomesencephalic cholinergic neurons appeared to correspond to the lateral tegmentoreticular tract. Fibers passed from these cholinergic cells ventrally through the lateral pontine tegmentum, in the region of the subcoeruleus, where they also appeared to innervate by fibres en passage the noncholinergic neurons of the region. A significant proportion of the pontomesencephalic cholinergic neurons were retrogradely labelled from the lateral pontine tegmentum.(ABSTRACT TRUNCATED AT 400 WORDS)

Cordotomy from the view points of retrogradely labelled cells

After injecting horseradish peroxidase into the facial nucleus regions containing orbicularis oculi motoneurons, labeled neuronal cell bodies were found in the lateral medullary reticular formation, pretectal olivary nucleus, sensory trigeminal nuclei, lateral and medial parabrachial nuclei, ventromedial reticular formation medial to the facial nucleus, red nucleus and its surroundings, anterior horn of the upper cervical cord, medullary raphe nuclei, oculomotor nucleus and its surroundings, nuclei of Darkschewitsch, Cajal and Edinger-Westphal, ventral part of the midbrain central gray, pontine tegmentum, lateral vestibular nucleus and deep layers of the superior colliculus.

Cerebellar connections of the trigeminal system in the pigeon ( Columbia livia)

Wheat germ-agglutinin conjugated horseradish peroxidase (WGA-HRP) was used to delineate trigeminocerebellar connections in the pigeon. Subnucleus oralis of the nucleus of the descending trigeminal tract (nTTD) is the exclusive origin of trigeminal mossy fibers, which terminate in lobules VIII and IXa. The trigemino-olivary projection originates from subnucleus interpolaris of nTTD, but the existence of an additional pathway relaying in the adjacent lateral reticular formation (i.e. the plexus of Horsley) cannot be excluded. Structures linking the trigeminal cerebellar projections to jaw motoneurons were identified within the cerebellar cortex, the deep cerebellar nuclei and the lateral medullary reticular formation, completing a trigeminocerebellar sensorimotor circuit for the jaw.

Inhibition of the responses of cat dorsal horn neurons to noxious skin heating by stimulation in medial or lateral medullary reticular formation.

Responses of single lumbar dorsal horn units to noxious radiant heating (50 degrees C, 10 s) of glabrous footpad skin were recorded in cats anesthetized with sodium pentobarbital and 70% nitrous oxide. The heat-evoked responses of 37/40 units were reduced during electrical stimulation (100 ms trains, 100 Hz, 3/s, 25-600 microA) in the medullary nucleus raphe magnus (NRM) and/or in laterally adjacent regions of the medullary reticular formation (MRF). Inhibition was elicited by stimulation in widespread areas of the medulla, but with greatest efficacy at ventrolateral sites. The magnitude of inhibition increased with graded increases in medullary stimulation intensity. Mean current intensities at threshold for inhibition or to produce 50% inhibition were higher for NRM than for MRF sites. Units' responses to graded noxious heat stimuli increased linearly from threshold (42-43 degrees C) to 52 degrees C. During NRM (5 units) or ipsilateral MRF stimulation (7 units), responses were inhibited such that the mean temperature-response functions were shifted toward higher temperatures with increased thresholds (1.5 degrees and 1 degree C, respectively) and reduced slopes (to 60% of control). Contralateral MRF stimulation had a similar effect in 4 units. Inhibitory effects of NRM and MRF stimulation were reduced (by greater than 25%) or abolished in 4/6 and 5/12 units, respectively, following systemic administration of the serotonin antagonist methysergide. Inhibitory effects from NRM, ipsi- and contralateral MRF were reduced or abolished in 2/9, 4/8 and 6/9 cases, respectively, following systemic administration of the noradrenergic antagonist phentolamine. These results confirm and extend previous studies of medullospinal inhibition and the role of monoamines, and are discussed in terms of analgesic mechanisms.

Vestibulospinal and reticulospinal interactions in the activation of back muscle EMG in the rat.

The effects of electrical stimulation of the lateral vestibular nucleus (LVN) and medullary reticular formation (RF) on electromyographic activity in axial muscles medial longissimus (ML) and lateral longissimus (LL) in the rat were studied. Long trains (150-500 ms) at 200-330 Hz and 20-100 microA were sufficient to activate ML and LL at latencies of 20-100 ms from the beginning of the train. Results of stimulation at 200-330 Hz to RF or LVN showed that muscle units were activated at a fixed latency from any effective pulse in the stimulus train. Using high frequency (1 kHz) trains of 3-6 pulses to LVN, EMG activity was detected at minimum latencies of 3.5-6 ms. When conduction times from the medulla to the spinal cord, and the spinal cord to the muscle are subtracted, this latency range is consistent with monosynaptic activation. In many cases, muscle units were recruited in order of size, with both RF and LVN stimulation. Combined stimulation of LVN and RF sites in n. gigantocellularis led to EMG activity in ML and LL at currents which were insufficient to evoke activity when presented singly. When stimulation of one site (300-400 ms train) was just sufficient to evoke a response, a shorter, overlapping train (100-150 ms) to the other site led to a higher rate of muscle activity that continued through the end of the long train, even after the short train had ended. In all cases, the effect of RF facilitating LVN was similar to the effect of LVN facilitating RF. The evidence for convergence between these two systems in the medulla and the spinal cord is discussed.

Autoradiographic study of descending pathways from the pontine reticular formation and the mesencephalic trigeminal nucleus in the rat.

Descending projections were studied in autoradiographically prepared material after injections of tritiated leucine in the pontine tegmentum of rats. Injections involving the medial pontine reticular formation resulted not only in labeling commissural fibers, the medial reticulospinal tract, and the dorsal cap of the inferior olive, but also, in two cases, in labeling a cerebellar projection that originated from a region near the midline and clearly dorsal to the nucleus reticularis tegmenti pontis. The labeled fibers passed ventral in the midline to the pontine gray, then laterally through the gray and into the middle cerebellar peduncle to terminate as mossy fibers primarily in the flocculus, lobulus simplex, and Crus I of the ansiform lobule. Injections involving the mesencephalic nucleus of the trigeminal nerve (Vmes), resulted in labeling of Probst's tract, which descends in the dorsolateral reticular formation. Probst's tract gave off extensive terminal branches to the lateral medullary reticular formation and weaker projections to restricted portions of the descending trigeminal nucleus, the solitary nucleus, and the hypoglossal nucleus. In one case, fibers could be traced into the dorsal horn of the upper cervical cord.