Lateral Reticular Formation Research Articles

Modulation of the swallowing reflex by stimulation of the gigantocellular reticular nucleus in the rat

ObjectivesThe gigantocellular reticular nucleus (Gi) projects to the nuclues of the solitary tract nucleus (NTS) and the lateral reticular formation (LRF) above the nucleus ambiguus. The swallowing central pattern generator comprises the NTS and the LRF. The present study examined whether stimulation of the Gi affects the swallowing reflex. MethodsExperiments were performed on urethane-anesthetized rats. The swallowing reflex was evoked by repetitive electrical stimulation of the superior laryngeal nerve and responses were recorded from the mylohyoid muscle on an electromyogram. The Gi was stimulated electrically. In addition, glutamate was injected into the Gi. The Friedman's test, followed by the Wilcoxon signed-rank test with Bonferroni correction, were used to assess the effects of electrical stimulation of the Gi. The Wilcoxon signed-rank test was used to assess the effects of glutamate injection into the Gi. Differences were considered significant at the P < 0.05 level. ResultsThe number of swallows was significantly increased or decreased by electrical stimulation of the Gi or after injection of glutamate into the Gi. In both electrical stimulation of the Gi and injection of glutamate into the Gi, the onset latency of the first swallow was prolonged when the number of swallows was decreased but showed no change when the number of swallows was increased. ConclusionsThe present results suggest that the Gi is involved in the control of swallowing.

Suppression of the Swallowing Reflex during Rhythmic Jaw Movements Induced by Repetitive Electrical Stimulation of the Dorsomedial Part of the Central Amygdaloid Nucleus in Rats.

A previous study indicated that the swallowing reflex is inhibited during rhythmic jaw movements induced by electrical stimulation of the anterior cortical masticatory area. Rhythmic jaw movements were induced by electrical stimulation of the central amygdaloid nucleus (CeA). The swallowing central pattern generator is the nucleus of the solitary tract (NTS) and the lateral reticular formation in the medulla. Morphological studies have reported that the CeA projects to the NTS and the lateral reticular formation. It is therefore likely that the CeA is related to the control of the swallowing reflex. The purpose of this study was to determine if rhythmic jaw movements driven by CeA had inhibitory roles in the swallowing reflex induced by electrical stimulation of the superior laryngeal nerve (SLN). Rats were anesthetised with urethane. The SLN was solely stimulated for 10 s, and the swallowing reflex was recorded (SLN stimulation before SLN + CeA stimulation). Next, the SLN and the CeA were electrically stimulated at the same time for 10 s, and the swallowing reflex was recorded during rhythmic jaw movements (SLN + CeA stimulation). Finally, the SLN was solely stimulated (SLN stimulation following SLN + CeA stimulation). The number of swallows was reduced during rhythmic jaw movements. The onset latency of the first swallow was significantly longer in the SLN + CeA stimulation than in the SLN stimulation before SLN + CeA stimulation and SLN stimulation following SLN + CeA stimulation. These results support the idea that the coordination of swallowing reflex with rhythmic jaw movements could be regulated by the CeA.

RELATIONSHIP between prandial drinking behavior and supersensitivity of salivary glands after superior salivatory nucleus lesions in RATS

Prandial drinking, an increase in the number of drinking responses and secondary or non-homeostatic polydipsia in the presence of dry food, is typically associated with a deficit in salivary secretion. This study investigates the degree of salivary gland supersensitivity to pilocarpine administration after lesions to the superior salivatory nucleus (SSN), the site of origin of the parasympathetic preganglionic neurons that innervate the submandibular-sublingual (S-S) salivary glands. The main aim was to determine if there is a relationship between the degree of glandular supersensitivity, as an index of secretory deficit, and the development of prandial drinking in lesioned rats. Results showed that following SSN lesions two subgroups of rats were obtained. One subgroup exhibited prandial drinking but the other was similar to the control group. The SSN-lesioned prandial drinking subgroup presented significantly greater supersensitivity than the SSN-lesioned non-prandial drinking rats; the non-prandial drinking subgroup, in turn, presented significantly more supersensitivity than controls. Additionally, S-S supersensitivity observed in rats that exhibited prandial drinking due to the sectioning of chorda tympani efferent axons was compared to that observed in rats exhibiting prandial drinking due to SSN lesions. It was found that both groups presented the same S-S supersensitivity curve. These results indicate that SSN lesions produce a gradation of S-S supersensitivity values that appear to run parallel to the degree of glandular secretory deficit caused by the lesions. Thus, only the rats with greater secretory deficit (greater supersensitivity) develop prandial drinking. These data support the idea that there is in fact a functional link between the lateral reticular formation of the brainstem (the region associated with the SSN) and S-S salivary glands.

Injections of Algesic Solutions into Muscle Activate the Lateral Reticular Formation: A Nociceptive Relay of the Spinoreticulothalamic Tract.

Although musculoskeletal pain disorders are common clinically, the central processing of muscle pain is little understood. The present study reports on central neurons activated by injections of algesic solutions into the gastrocnemius muscle of the rat, and their subsequent localization by c-Fos immunohistochemistry in the spinal cord and brainstem. An injection (300μl) of an algesic solution (6% hypertonic saline, pH 4.0 acetate buffer, or 0.05% capsaicin) was made into the gastrocnemius muscle and the distribution of immunolabeled neurons compared to that obtained after control injections of phosphate buffered saline [pH 7.0]. Most labeled neurons in the spinal cord were found in laminae IV-V, VI, VII and X, comparing favorably with other studies, with fewer labeled neurons in laminae I and II. This finding is consistent with the diffuse pain perception due to noxious stimuli to muscles mediated by sensory fibers to deep spinal neurons as compared to more restricted pain localization during noxious stimuli to skin mediated by sensory fibers to superficial laminae. Numerous neurons were immunolabeled in the brainstem, predominantly in the lateral reticular formation (LRF). Labeled neurons were found bilaterally in the caudalmost ventrolateral medulla, where neurons responsive to noxious stimulation of cutaneous and visceral structures lie. Immunolabeled neurons in the LRF continued rostrally and dorsally along the intermediate reticular nucleus in the medulla, including the subnucleus reticularis dorsalis caudally and the parvicellular reticular nucleus more rostrally, and through the pons medial and lateral to the motor trigeminal nucleus, including the subcoerulear network. Immunolabeled neurons, many of them catecholaminergic, were found bilaterally in the nucleus tractus solitarii, the gracile nucleus, the A1 area, the CVLM and RVLM, the superior salivatory nucleus, the nucleus locus coeruleus, the A5 area, and the nucleus raphe magnus in the pons. The external lateral and superior lateral subnuclei of the parabrachial nuclear complex were consistently labeled in experimental data, but they also were labeled in many control cases. The internal lateral subnucleus of the parabrachial complex was labeled moderately. Few immunolabeled neurons were found in the medial reticular formation, however, but the rostroventromedial medulla was labeled consistently. These data are discussed in terms of an interoceptive, multisynaptic spinoreticulothalamic path, with its large receptive fields and role in the motivational-affective components of pain perceptions.

Anatomical organization of descending cortical projections orchestrating the patterns of cortically induced rhythmical jaw muscle activity in guinea pigs

Repetitive electrical microstimulation to the cortical masticatory area (CMA) evokes distinct patterns of rhythmical jaw muscle activities (RJMAs) in animals. This study aimed to investigate the characteristics of the descending projections from the CMA, associated with distinct patterns of RJMAs, to the thalamus, midbrain, pons and medulla in guinea pigs. RJMAs with continuous masseter and digastric bursts (CB-RJMAs) and stimulus-locked digastric sub-bursts (SLB-RJMAs) were induced from the anterior and posterior areas of the rostral region of the lateral agranular cortex, and chewing-like RJMAs from the rostral region of the granular cortex. Anterograde tracer, biotinylated dextran amine, was injected into the three cortical areas. The cortical area inducing CB-RJMAs had strong ipsilateral projections to the motor thalamus, red nucleus, midbrain reticular formation, superior colliculus, parabrachial nucleus, and supratrigeminal region, and contralateral projections mainly to the lateral reticular formation around the trigeminal motor nucleus (Vmo). The cortical area inducing SLB-RJMAs had moderate projections to the motor thalamus and lateral reticular formation around the Vmo, but few projections to the midbrain nuclei. The cortical area inducing chewing-like RJMAs had strong projections to the ipsilateral sensory thalamus and contralateral trigeminal sensory nuclei, and moderate projections to the lateral reticular formation. The three cortical areas consistently had few projections to the ventromedial reticular formation. The present study demonstrates that multiple direct and indirect descending projections from the CMA onto the premotor systems connecting the trigeminal motoneurons represent the neuroanatomical repertoires for generating RJMAs during the distinct phases of natural ingestive behavior.

Direct reticular projections of trigeminal sensory fibers immunoreactive to CGRP: potential monosynaptic somatoautonomic projections.

Few trigeminal sensory fibers project centrally beyond the trigeminal sensory complex, with only projections of fibers carried in its sensory anterior ethmoidal (AEN) and intraoral nerves described. Fibers of the AEN project into the brainstem reticular formation where immunoreactivity against substance P and CGRP are found. We investigated whether the source of these peptides could be from trigeminal ganglion neurons by performing unilateral rhizotomies of the trigeminal root and looking for absence of label. After an 8–14 days survival, substance P immunoreactivity in the trigeminal sensory complex was diminished, but we could not conclude that the sole source of this peptide in the lateral parabrachial area and lateral reticular formation arises from primary afferent fibers. Immunoreactivity to CGRP after rhizotomy however was greatly diminished in the trigeminal sensory complex, confirming the observations of others. Moreover, CGRP immunoreactivity was nearly eliminated in fibers in the lateral parabrachial area, the caudal ventrolateral medulla, both the peri-ambiguus and ventral parts of the rostral ventrolateral medulla, in the external formation of the nucleus ambiguus, and diminished in the caudal pressor area. The nearly complete elimination of CGRP in the lateral reticular formation after rhizotomy suggests this peptide is carried in primary afferent fibers. Moreover, the arborization of CGRP immunoreactive fibers in these areas mimics that of direct projections from the AEN. Since electrical stimulation of the AEN induces cardiorespiratory adjustments including an apnea, peripheral vasoconstriction, and bradycardia similar to those seen in the mammalian diving response, we suggest these perturbations of autonomic behavior are enhanced by direct somatic primary afferent projections to these reticular neurons. We believe this to be first description of potential direct somatoautonomic projections to brainstem neurons regulating autonomic activity.

High resolution MRI anatomy of the cat brain at 3Tesla

Feline models of neurologic diseases, such as lysosomal storage diseases, leukodystrophies, Parkinson's disease, stroke and NeuroAIDS, accurately recreate many aspects of human disease allowing for comparative study of neuropathology and the testing of novel therapeutics. Here we describe in vivo visualization of fine structures within the feline brain that were previously only visible post mortem. 3Tesla MR images were acquired using T1-weighted (T1w) 3D magnetization-prepared rapid gradient echo (MPRAGE) sequence (0.4mm isotropic resolution) and T2-weighted (T2w) turbo spin echo (TSE) images (0.3mm×0.3mm×1mm resolution). Anatomic structures were identified based on feline and canine histology. T2w high resolution MR images with detailed structural identification are provided in transverse, sagittal and dorsal planes. T1w MR images are provided electronically in three dimensions for unrestricted spatial evaluation. Many areas of the feline brain previously unresolvable on MRI are clearly visible in three orientations, including the dentate, interpositus and fastigial cerebellar nuclei, cranial nerves, lateral geniculate nucleus, optic radiation, cochlea, caudal colliculus, temporal lobe, precuneus, spinocerebellar tract, vestibular nuclei, reticular formation, pyramids and rostral and middle cerebral arteries. Additionally, the feline brain is represented in three dimensions for the first time. These data establish normal appearance of detailed anatomical structures of the feline brain, which provide reference when evaluating neurologic disease or testing efficacy of novel therapeutics in animal models.

Peripheral administration of tau aggregates triggers intracerebral tauopathy in transgenic mice

Peripheral administration of tau aggregates triggers intracerebral tauopathy in transgenic mice

Basic techniques for long distance axon tracing in the spinal cord

The regeneration of axons after a spinal cord injury or disease is attracting a significant amount of interest among researchers. Being able to assess these axons in terms of morphology, length and origin is essential to our understanding of the regeneration process. Recently, two specific axon tracers have gained much recognition; biotinylated dextran amine (BDA) 10 kDa as an anterograde tracer and cholera toxin-B as a retrograde tracer. However, there are still several complexities when using these tracers, including the volume that should be administered and the best administration site so that a significant amount of axons are labeled in the area of interest. In this article, we describe some simple procedures for injecting the tracers and detecting them. We also quantified the number of axons at different locations of the spinal cord. Our results show axons labeled from motor cortex injections traveled down to the lumbosacral spinal cord in 2 weeks, while BDA injections into the lateral vestibular nucleus and reticular formation took 3 weeks to label axons in the lumbosacral spinal cord. Moreover, this protocol outlines some basic procedures that could be used in any laboratory and gives insight into the number of axons labeled and how procedures could be tailored to meet specific researcher's needs.

State-dependent and reflex drives to the upper airway: basic physiology with clinical implications

The root cause of the most common and serious of the sleep disorders is impairment of breathing, and a number of factors predispose a particular individual to hypoventilation during sleep. In turn, obstructive hypopneas and apneas are the most common of the sleep-related respiratory problems and are caused by dysfunction of the upper airway as a conduit for airflow. The overarching principle that underpins the full spectrum of clinical sleep-related breathing disorders is that the sleeping brain modifies respiratory muscle activity and control mechanisms and diminishes the ability to respond to respiratory distress. Depression of upper airway muscle activity and reflex responses, and suppression of arousal (i.e., "waking-up") responses to respiratory disturbance, can also occur with commonly used sedating agents (e.g., hypnotics and anesthetics). Growing evidence indicates that the sometimes critical problems of sleep and sedation-induced depression of breathing and arousal responses may be working through common brain pathways acting on common cellular mechanisms. To identify these state-dependent pathways and reflex mechanisms, as they affect the upper airway, is the focus of this paper. Major emphasis is on the synthesis of established and recent findings. In particular, we specifically focus on 1) the recently defined mechanism of genioglossus muscle inhibition in rapid-eye-movement sleep; 2) convergence of diverse neurotransmitters and signaling pathways onto one root mechanism that may explain pharyngeal motor suppression in sleep and drug-induced brain sedation; 3) the lateral reticular formation as a key hub of respiratory and reflex drives to the upper airway.

Brain-derived neurotrophic factor (BDNF) and polysialylated-neural cell adhesion molecule (PSA-NCAM): codistribution in the human brainstem precerebellar nuclei from prenatal to adult age

Occurrence and distribution of the neurotrophin brain-derived neurotrophic factor (BDNF) and polysialylated-neural cell adhesion molecule (PSA-NCAM), a neuroplasticity marker known to modulate BDNF signalling, were examined by immunohistochemistry in the human brainstem precerebellar nuclei at prenatal, perinatal and adult age. Western blot analysis performed in human brainstem showed for both molecules a single protein band compatible with the molecular weight of the dimeric form of mature BDNF and with that of PSA-NCAM. Detectability of both molecules up to 72 h post-mortem was also assessed in rat brain. In neuronal perikarya, BDNF-like immunoreactivity (LI) appeared as intracytoplasmic granules, whereas PSA-NCAM-LI appeared mostly as peripheral staining, indicative of membrane labelling; immunoreactivity to both substances also labelled nerve fibres and terminals. BDNF- and PSA-NCAM-LI occurred in the external cuneate nucleus, perihypoglossal nuclei, inferior olive complex, arcuate nucleus, lateral reticular formation, vestibular nuclei, pontine reticulotegmental and paramedian reticular nuclei, and pontine basilar nuclei. With few exceptions, for both substances the distribution pattern detected at prenatal age persisted later on, though the immunoreactivity appeared often higher in pre- and full-term newborns than in adult specimens. The results obtained suggest that BDNF operates in the development, maturation, maintenance and plasticity of human brainstem precerebellar neuronal systems. They also imply a multiple origin for the BDNF-LI of the human cerebellum. The codistribution of BDNF- and PSA-NCAM-LI in analyzed regions suggests that PSA-NCAM may modulate the functional interaction between BDNF and its high and low affinity receptors, an issue worth further analysis, particularly in view of the possible clinical significance of neuronal trophism in cerebellar neurodegenerative disorders.

Modulation of exteroceptive suppression periods in human jaw‐closing muscles by subanaesthetic dose of propofol

Exteroceptive suppression (ES) periods in human jaw-closing muscles can be conditioned by a wide range of somatosensory stimuli and cognitive states. The aim of this study was to examine the effects of subanaesthetic doses of midazolam, ketamine and propofol on the short latency (ES1) and long latency (ES2) reflex in the jaw-closing muscles. First, we tried to evaluate the various methodological criteria for ES recording. We then examined the effect of subanaesthetic doses of midazolam (0·035 mg kg(-1)), ketamine (0·30 mg kg(-1)) and propofol (0·35 mg kg(-1)) on these reflexes of recording left masseter and temporalis muscle. ES duration did not differ greatly in the present study, recorded with the correct adjustment of stimulating and recording conditions. None of the subanaesthetic doses of the agents influenced ES1, and no significant effects on ES2 were observed with midazolam and ketamine. However, significant inhibitory change was observed in ES2 with propofol. ES2 is thought to be mediated by afferents, which descend in the spinal trigeminal tract and connect with a polysynaptic chain of excitatory interneurones located in the lateral reticular formation. Our observations indicate that propofol is uniquely effective not only through involvement of the gamma-aminobutyric acid type A receptor, but also through a range of other effects.

Nonphosphorylated neurofilament protein is expressed by scattered neurons in the vestibular and precerebellar brainstem

Vestibular information is essential for the control of posture, balance, and eye movements. The vestibular nerve projects to the four nuclei of the vestibular nuclear complex (VNC), as well as to several additional brainstem nuclei and the cerebellum. We have found that expression of the calcium-binding proteins calretinin (CR) and calbindin (CB), and the synthetic enzyme for nitric oxide synthase (nNOS) define subdivisions of the medial vestibular nucleus (MVe) and the nucleus prepositus (PrH), in cat, monkey, and human. We have asked if the pattern of expression of nonphosphorylated neurofilament protein (NPNFP) might define additional subdivisions of these or other nuclei that participate in vestibular function. We studied the distribution of cells immunoreactive to NPNFP in the brainstems of 5 cats and one squirrel monkey. Labeled cells were scattered throughout the four nuclei of the VNC, as well as in PrH, the reticular formation (RF) and the external cuneate nucleus. We used double-label immunofluorescence to visualize the distribution of these cells relative to other neurochemically defined subdivisions. NPNFP cells were excluded from the CR and CB regions of the MVe. In PrH, NPNFP and nNOS were not colocalized. Cells in the lateral vestibular nucleus and RF colocalized NPNFP and a marker for glutamatergic neurons. We also found that the cholinergic cells and axons of cranial nerve nuclei 3, 4, 6, 7,10 and 12 colocalize NPNFP. The data suggest that NPNFP is expressed by a subset of glutamatergic projection neurons of the vestibular brainstem. NPNFP may be a marker for those cells that are especially vulnerable to the effects of normal aging, neurological disease or disruption of sensory input.

Distribution of premotoneurons for jaw-closing and jaw-opening motor nucleus receiving contacts from axon terminals of primary somatosensory cortical neurons in rats

To clarify features of direct projections from the primary somatosensory cortex (S1) to premotoneurons for the jaw-closing (JC) and jaw-opening (JO) components of the trigeminal motor nucleus, biotinylated dextranamine (BDA) and Fluorogold (FG) were used as the anterograde and retrograde tracers. The BDA and FG injections were made in the S1 and the JC or JO component, respectively, in rats. The distribution of FG-labeled JC and JO premotoneurons receiving contact(s) from BDA-labeled axon terminals of S1 neurons was quantitatively examined; the contacts were identified microscopically by using a X100 oil immersion objective. The largest and second largest numbers of JC and JO premotoneurons with contact(s) were found in the lateral reticular formation at the levels of the caudal pons and the medulla oblongata (cpmLRt) and trigeminal oral nucleus (Vo) bilaterally, and they comprised about 80% of the total premotoneurons with contact(s). The percentage of premotoneurons with contact(s) was higher in the Vo than in the cpmLRt for both JC and JO premotoneurons. Most of the JC or JO premotoneurons found in the nucleus of the solitary tract, inter- and supratrigeminal regions, mesencephalic trigeminal nucleus, parabrachial nucleus and reticular formation medial to the JO component of the trigeminal motor nucleus hardly received contact(s) from S1 neurons. This suggests that the contribution of S1 to the control of jaw movements is mediated via JC and JO premotoneurons located primarily in the cpmLRt and Vo areas of the brainstem.

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.

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.

Some aspects of the organization of the output of the motor cortex.

The precentral motor cortex in the macaque is defined here as that portion of the precentral motor-sensory areas which projects to the intermediate zone and motor neuronal cell groups in the spinal cord and their bulbar counterparts, i.e. the lateral reticular formation and motor nuclei of the lower brainstem. In this respect the precentral motor cortical areas differ from postcentral areas such that the descending projections from the latter are focused on the spinal dorsal horn and the spinal V complex. Differences in the distribution of the corticospinal fibres in different species are mentioned and differences in findings obtained by means of different tracing techniques are discussed. The projections from the precentral motor cortex to various brain-stem cell groups are also discussed and the areas of origin of these projections are delineated. The presence of branching neurons distributing collaterals to several of these areas is considered.

From neuroanatomy to gene therapy: searching for new ways to manipulate the supraspinal endogenous pain modulatory system.

The endogenous pain modulatory system is a complex network of brain areas that control nociceptive transmission at the spinal cord by inhibitory and facilitatory actions. The balance between these actions ensures effective modulation of acute pain, while during chronic pain the pronociceptive effects appear to prevail. The mechanisms underlying this imbalance were studied as to the role of two medullary components of the pain modulatory system: the dorsal reticular nucleus and the caudal ventrolateral medulla, which function primarily as pronociceptive and antinociceptive centres, respectively. Both areas are connected with the spinal dorsal horn by closed reciprocal loops. In the spino-dorsal reticular nucleus loop, the ascending branch is strongly inhibited by spinal GABAergic neurons, which may act as a buffering system of the dorsal reticular nucleus-centred amplifying effect. In the spino-caudal ventrolateral medulla loop, the ascending branch is under potent excitation of substance P (SP) released from primary afferents, which is likely to trigger the intense descending inhibition detected in acute pain. During chronic pain, the activity in the lateral reticular formation of the caudal ventrolateral medulla changes, so that the action of the caudal ventrolateral medulla upon SP-responsive spinal neurons shifts from inhibitory to excitatory. The mechanisms of this modulatory shift are unknown but probably relate to the decreased expression of micro-opioid, delta-opioid and GABAB receptors. Normalizing receptor expression in the caudal ventrolateral medulla or controlling noci-evoked activity at the dorsal reticular nucleus or caudal ventrolateral medulla by interfering with neurotransmitter release is now possible by the use of gene therapy, an approach that stands out as a unique tool to manipulate the supraspinal endogenous pain control system.

The somatotopic organization of trigeminal premotoneurons in the cat brainstem

This study was performed to complement the results of prior intracellular recording and labeling studies by investigating the general distribution pattern of trigeminal premotoneurons in the cat brainstem using the retrograde tracing methods. The results of the present study reconfirmed the presence of premotoneurons in the trigeminal principal and oral nuclei following horseradish peroxidase injections into the jaw-opening (JO) or jaw-closing (JC) nucleus. Furthermore, we found that labeled cells from the JO nucleus and JC nucleus located in the reticular regions surrounding the trigeminal motor nucleus (Vmo; Vmo shell region) were arranged in a topographic fashion, while those in the parabrachial nucleus, supratrigeminal nucleus, lateral reticular formation caudal to the shell region and raphe nuclei were intermingled with each other. The labeling in the individual nuclei was bilateral with an ipsilateral predominance to each injection site, with the exception of the mesencephalic trigeminal nucleus, where the labeling was ipsilateral to the injection site in the JC nucleus. These results, combined with the data of the previous intracellular tracing studies, indicate that based on the presence of somatotopic organization, premotoneurons can be largely divided into two groups; those projecting to either the JO or the JC nucleus and those projecting to the two nuclei, and we offer the suggestion that roles of premotoneurons for jaw movements differ among the individual nuclei.

Taste‐evoked Fos expression in nitrergic neurons in the nucleus of the solitary tract and reticular formation of the rat

The current investigation used double labeling for NADPHd and Fos-like immunoreactivity to define the relationship between nitric oxide synthase-containing neural elements and taste-activated neurons in the nucleus of the solitary tract (NST) and subjacent reticular formation (RF). Stimulation of awake rats with citric acid and quinine resulted in significant increases in the numbers of double-labeled neurons in both the NST and RF, suggesting that some medullary gustatory neurons utilize nitric oxide (NO) as a transmitter. Overall, double-labeled neurons were most numerous in the caudal reaches of the gustatory zone of the NST, where taste neurons receive inputs from the IXth nerve, suggesting a preferential role for NO neurons in processing gustatory inputs from the posterior oral cavity. However, double-labeled neurons also exhibited a preferential distribution depending on the gustatory stimulus. In the NST, double-labeled neurons were most numerous in the rostral central subnucleus after either stimulus but had a medial bias after quinine stimulation. In the RF, after citric acid stimulation, there was a cluster of double-labeled neurons with distinctive large soma in the parvicellular division of the lateral RF, subjacent to the rostral tip of NST. In contrast, in response to quinine, there was a cluster of double-labeled neurons with much smaller soma in the intermediate zone of the medial RF, a few hundred micrometers caudal to the citric acid cluster. These differential distributions of double-labeled neurons in the NST and RF suggest a role for NO in stimulus-specific gustatory autonomic and oromotor reflex circuits.