Medullary Reticular Formation Research Articles

Defining projections from the caudal pressor area of the caudal ventrolateral medulla

We previously defined a functional area in the caudal medulla oblongata that elicits an increase in arterial pressure when stimulated (Sun and Panneton [2002] Am. J. Physiol. 283:R768-R778). In the present study, anterograde and retrograde tracing techniques were used to investigate the projections of this caudal pressor area (CPA) to the medulla and pons. Injections of biotinylated dextran amine into the CPA resulted in numerous labeled fibers with varicosities in the ipsilateral subnucleus reticularis dorsalis, commissural subnucleus of the nucleus tractus solitarii, lateral medulla, medial facial nucleus, A5 area, lateral vestibular nucleus, and internal lateral subnucleus of the parabrachial complex. Sparser projections were found ipsilaterally in the pressor and depressor areas of the medulla and the spinal trigeminal nucleus and contralaterally in the CPA. Injections of the retrograde tracer Fluoro-Gold into these areas labeled neurons in the CPA as well as the nearby medullary dorsal horn and reticular formation. However, we conclude that the CPA projects preferentially to the subnucleus reticularis dorsalis, commissural nucleus tractus solitarii, lateral medulla, A5 area, and internal lateral parabrachial nucleus. Weaker projections were seen to the CVLM and RVLM and to the contralateral CPA. The projection to the facial nucleus arises from nearby reticular neurons, whereas projections to the vestibular nucleus arise from the lateral reticular nucleus. Labeled neurons in the CPA consisted mostly of small bipolar and some triangular neurons. The projection to the CVLM, or to A5 area, may provide for the increase in arterial pressure with CPA stimulation. However, most of the projections described herein are to nuclei implicated in the processing of noxious information. This implies a unique role for the CPA in somatoautonomic regulation.

Rapidly progressive fatal respiratory failure (Ondine’s curse) in the lateral medullary syndrome

A 70-year-old man presented with unilateral lateral medullary infarction, and then died of rapidly progressive respiratory failure within a day. The clinical manifestations were hiccups, hoarseness, dysarthria, nystagmus, left central facial paralysis, paralysis of the left soft palate, dysphagia, decreased superficial sensation over the right face and upper limb, and cerebellar ataxia in the left upper and lower limbs. The arterial blood gas analysis revealed mild hypoventilation. Soon thereafter, an apneic episode occurred during a sleep and advanced to ataxic respiration, and the patient Died. Pathologically, there were fresh ischemic infarction localized to the left dorsolateral area of the upper medulla, caused by atherothrombotic occlusion of the left vertebral artery. These foci were in the areas including the medullary reticular formation, the solitary nucleus, the intramedullary fibers of the vagus nerve, and the nucleus ambiguus on the left side. We attributed the fatal acute progressive respiratory impairment in the present case to impairment of the automatic respiratory system (Ondine’s curse) rather than the voluntary respiratory system.

Granulocyte Macrophage Colony-Stimulating Factor Regulates Activity of the Nervous System

Objectives: The peripheral administration of granulocyte macrophage colony-stimulating factor (GM-CSF), widely used for the treatment of cytopenias, is often associated with neurological effects [Lieschke et al., N Engl J Med 1992;327:28–34]. This cytokine has recently been reported to affect neurotransmitter metabolism in the nervous system [Bianchi, Neuroreport 1997;8:3587–3590]. To further investigate the neuromodulatory effect of GM-CSF we studied the influence of GM-CSF on the efferent electric activity in the splenic nerve and the integral neuronal activity in medullary gigantocellular reticular formation (MGRF) in rats. Methods: Anaesthetized (sodium thiopental 70 mg/kg, i.p.) Wistar rats were injected subcutaneously with 1 µg/kg of hr GM-CSF. Efferent electric activity in the splenic nerve and integral electric activity in MGRF were analyzed. The effectiveness of the applied dose of GM-CSF was verified by determining the elevation of the white blood cell count in peripheral blood 60 min after injection. Results: We found that GM-CSF increases efferent electric activity in the splenic nerve and decreases that of MGRF as is evident by the frequency of electric discharges. The latency of both effects was 5–15 min. Conclusions: This data support the view that GM-CSF exerts a neuromodulatory effect and may provide a new link of neuroimmune communication.

Medullary reticulospinal tract mediating a generalized motor inhibition in cats: iii. functional organization of spinal interneurons in the lower lumbar segments

The previous report of intracellular recording of hindlimb motoneurons in decerebrate cats [ Neuroscience 103 (2001) 511] has suggested that the following mechanisms are involved in a generalized motor inhibition induced by stimulating the medullary reticular formation. First, the motor inhibition, which was prominent in the late latency (30–80 ms), can be ascribed to the inhibitory effects in parallel to motoneurons and to interneuronal transmission in reflex pathways. Second, both a group of interneurons receiving inhibition from flexor reflex afferents and a group of Ib interneurons mediate the late inhibitory effects upon the motoneurons. To substantiate the above mechanisms of motor inhibition we examined the medullary stimulus effects upon intracellular ( n=55) and extracellular ( n=136) activity of spinal interneurons recorded from the lower lumbar segments (L6–L7). Single pulses or stimulus trains (1–3) pulses, with a duration of 0.2 ms and intensity of 20–50 μA) applied to the medullary nucleus reticularis gigantocellularis evoked a mixture of excitatory and inhibitory effects with early (<20 ms) and late (>30 ms) latencies. The medullary stimulation excited 55 interneurons (28.8%) with a late latency. Thirty-nine of the cells, which included 10 Ib interneurons, were inhibited by volleys in flexor reflex afferents (FRAs). These cells were mainly located in lamina VII of Rexed. On the other hand, the late inhibitory effects were observed in 67 interneurons (35.1%), which included cells mediating reciprocal Ia inhibition, non-reciprocal group I (Ib) inhibition, recurrent inhibition and flexion reflexes. Intracellular recording revealed that the late inhibitory effects were due to inhibitory postsynaptic potentials with a peak latency of about 50 ms and a duration of 50–60 ms. The inhibitory effects were attenuated by volleys in FRAs. Neither excitatory nor inhibitory effects with a late latency were observed in 69 (36.1%) cells which were located in the intermediate region and dorsal horn. These results suggest the presence of a functional organization of the spinal cord with respect to the production of the generalized motor inhibition. Lamina VII interneurons that receive inhibition from volleys in FRAs possibly mediate the postsynaptic inhibition from the medullary reticular formation in parallel to motoneurons and to interneurons in reflex pathways.

Immunohistochemical study on the distribution of MnSOD in the central nervous system of the transgenic mice expressing a human Cu/Zn SOD mutation

In the present study, we used the SOD1 G93A mutant transgenic mice as an animal model of amyotrophic lateral sclerosis (ALS) and performed immunohistochemical studies to investigate the changes of MnSOD in the central nervous system of transgenic mice at the age of 8, 13, and 18 weeks. In the spinal cord of wild-type SOD1 (wtSOD1) and SOD1 G93A transgenic mice, MnSOD-immunoreactive neurons were distributed mainly in the anterior horn, although they were also observed in the posterior horn. The staining intensity of MnSOD was significantly increased in the spinal cord of SOD1 G93A transgenic mice at presymptomatic and symptomatic stage. In the brainstem of symptomatic SOD1 G93A transgenic mice, significantly increased immunoreactivity for MnSOD was observed in abducens nucleus, facial nucleus, dorsal motor nucleus of vagus, hypoglossal nucleus, medullary and pontine reticular formation, superior and inferior olivary nucleus, and cochlear nucleus. The present study provides the first evidence that MnSOD immunoreactivity was increased in the central nervous system of SOD G93A transgenic mice, suggesting that mitochondria may play an important role in the pathogenesis and progress of ALS. The mechanisms underlying the increased immunoreactivity for MnSOD, and the functional implications of these increases, require elucidation.

Brain afferents to the lateral caudal ventrolateral medulla: a retrograde and anterograde tracing study in the rat

The ventrolateral medulla (VLM) modulates autonomic functions, motor reactions and pain responses. The lateralmost part of the caudal VLM (VLMlat) was recently shown to be the VLM area responsible for pain modulation. In the present study, the brain sources of VLMlat afferent fibers were determined by tract-tracing techniques. Following injection of cholera toxin subunit B into the VLMlat, retrogradely labeled neurons in the forebrain occurred at the somatosensory, insular, motor, limbic and infralimbic cortices, and at the central amygdaloid nucleus. Retrogradely labeled neurons in diencephalic regions were observed in the lateral hypothalamus, posterior hypothalamus and paraventricular nucleus. In the brainstem, retrograde labeling occurred at the periaqueductal gray, red nucleus, parabrachial area, nucleus raphe magnus, nucleus tractus solitarii, lateral reticular nucleus and dorsal and ventral medullary reticular formation. In the cerebellum, retrogradely labeled neurons occurred at the lateral nucleus. Following injections of the anterograde tracer biotinylated dextran amine (BDA) into the lateral hypothalamus or paraventricular nucleus, anterogradely labeled fibers were mainly observed in the VLMlat. Injections of BDA into the periaqueductal gray, red nucleus or lateral nucleus of the cerebellum resulted in anterograde labeling in the VLMlat and lateral reticular nucleus. The present study gives an account of the brain regions putatively involved in triggering the modulatory actions elicited from the VLMlat. These include areas committed to somatosensory processing, autonomic control, somatic and visceral motor activity and affective reactions. The findings suggest that the VLMlat may play a major homeostatic role in the integration of nociception with other brain functions.

Transneuronal tracing of neural pathways influencing both diaphragm and genioglossal muscle activity in the ferret.

In prior experiments that employed the transneuronal transport of isogenic recombinants of pseudorabies virus (PRV), we demonstrated that neurons located ventrally in the medial medullary reticular formation (MRF) of the ferret provide collateralized projections to both diaphragm and abdominal muscle motoneurons as well as to multiple abdominal muscle motoneuron pools. The goal of the present study was to determine whether single MRF neurons also furnish inputs to diaphragm motoneurons and those innervating an airway muscle with inspiratory-related activity: the tongue protruder genioglossus. For this purpose, PRV recombinants expressing unique reporters (beta-galactosidase or enhanced green fluorescent protein) were injected into either the diaphragm or the genioglossal muscle. The virus injections produced transneuronal infection of overlapping populations of MRF neurons. A small proportion of these neurons (<15%) was infected by both PRV recombinants, which indicated that they provide collateralized inputs to genioglossal and diaphragm motoneurons. These findings show that, whereas some MRF neurons simultaneously influence the activity of upper airway and respiratory pump muscles, other cells in this brain stem region independently contribute to diaphragm and genioglossal muscle contraction regulation.

Brainstem Substrates of Sympatho-Motor Circuitry Identified Using Trans-Synaptic Tracing with Pseudorabies Virus Recombinants

Previous physiological investigations have suggested the existence of a neural circuit that coordinates activation of motor and autonomic efferents before or at the onset of exercise. Traditionally these circuits have been postulated to involve forebrain areas. However, overlapping populations of medullary reticular formation neurons that participate in motor or autonomic control have been described previously, suggesting that individual pontomedullary reticular formation neurons may coordinate both motor and autonomic responses. We tested this hypothesis by conducting transneuronal retrograde tracing of motor and sympathetic nervous system pathways in rats using recombinant strains of pseudorabies virus (PRV). A PRV strain expressing the green fluorescent protein (PRV-152) was injected into the left gastrocnemius muscle, which was surgically sympathectomized, whereas another recombinant (PRV-BaBlu) was injected into the left adrenal gland. Immunofluorescence methods using monospecific antisera and distinct fluorophores identified neurons infected with one or both of the recombinants. Brainstem neurons coinfected with both PRV recombinants, which presumably had collateralized projections to both adrenal sympathetic preganglionic neurons and gastrocnemius motoneurons, were observed in several areas of the pontomedullary reticular formation. The largest number of such neurons was located in the rostral ventromedial medulla within the ventral gigantocellular nucleus, gigantocellular nucleus pars alpha, raphe obscurus, and raphe magnus. These neurons are candidates for relaying central command signals to the spinal cord.

Cardiovascular responses to chemical stimulation of the lateral tegmental field and adjacent medullary reticular formation in the rat

Relatively few studies have been done to characterize cardiovascular responses to the chemical stimulation of sites located in the medullary lateral tegmental field (LTF) and most of them have been carried out in anesthetized animals. Our experiments were carried out in decerebrated, artificially ventilated, adult male Wistar rats. In the LTF, two types of cardiovascular responses were elicited. One type consisted of pressor responses accompanied by bradycardia. Such responses were elicited from a region 0.4 mm caudal to 0.8 mm rostral to the calamus scriptorius (CS); maximum responses were elicited from a site 0.6 mm rostral to the CS, 1.2 mm lateral to the midline and 1.2 mm deep from the dorsal medullary surface. Another type consisted of pressor responses without any change in heart rate; such responses were elicited from a region 1–1.6 mm rostral to the CS. Nucleus ambiguus (nAmb) and dorsal motor nucleus of the vagus (nDMX) and the reticular formation surrounding these areas were the main sites from which bradycardia (accompanied by either no or small changes in BP) was elicited. In the nAmb, maximum bradycardia was elicited from a site 0.6 mm rostral to the CS, 1.8 mm lateral to the midline and 2.4 mm deep from the dorsal medullary surface. In the nDMX, most prominent bradycardic responses were elicited at 0–0.6 mm rostral to the CS, and 0.6 mm lateral to the midline and 1 mm deep from the dorsal medullary surface. Cardiovascular effects elicited from sites in other well-known areas, such as the rostral ventrolateral medullary pressor area (RVLM) and caudal ventrolateral medullary depressor area (CVLM), and the nucleus tractus solitarius (nTS) were also included for comparison of different responses. These results are expected to prove useful in studies in which the microinjection technique is used to characterize cardiovascular responses.

Efferent subcortical projections of the laryngeal motorcortex in the rhesus monkey

In order to better understand the descending voluntary vocal control pathway, the efferent subcortical projections of the laryngeal motorcortex were studied in the rhesus monkey ( Macaca mulatta). For this purpose, the left motorcortex was exposed in three animals under narcosis. By electrical brain stimulation, sites were identified yielding vocal fold adduction. Effective sites were injected with the anterograde tracer biotin dextran amine. Subcortical projections could be traced within the forebrain to the putamen, caudate nucleus, claustrum, zona incerta, field H of Forel and a number of thalamic nuclei, with the heaviest projections to the nuclei ventralis lateralis, ventralis posteromedialis, including its parvocellular part, medialis dorsalis, centralis medialis, centrum medianum and reuniens. In the midbrain, labeling was found in the deep mesencephalic nucleus. In the lower brainstem, fibers terminated in the pontine and medullary reticular formation, locus coeruleus, nucleus subcoeruleus, medial parabrachial nucleus, nucleus of the spinal trigeminal tract, solitary tract nucleus and facial nucleus. No projections were found to the nucl. ambiguus. The fact that monkeys, in contrast to humans, lack a direct connection of the motorcortex with the laryngeal motoneurons suggests that this connection has evolved in the last few million years and might represent one of the factors that made speech evolution possible.

Anatomic relationships of the human nucleus of the solitary tract in the medulla oblongata: a DiI labeling study

The nucleus of the solitary tract (nTS) is a major site of brainstem control of vital functions (e.g., cardiovascular reflexes and respiration). We examined anatomic relationships of the human nucleus of the solitary tract, using a bidirectional lipophilic fluorescent tracer 1-1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) in 10 postmortem human fetal midgestational medullae oblongatae. Labeling by diffusion of DiI from the nucleus of the solitary tract included: (1) neuropil of all future subdivisions of the nucleus of the solitary tract ipsilateral to the DiI crystal; (2) stellate cells in the caudal raphe at the junction of the nucleus raphe pallidus and the arcuate nucleus at the ventral medullary surface, as well as single fibers along the caudal raphe and the arcuate nucleus; (3) cells and fibers in other medullary areas related to autonomic and respiratory control, including the dorsal motor nucleus of the vagus, nucleus ambiguus complex/ventral respiratory group, rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM), and medullary reticular formation. The pattern of connections of the nucleus of the solitary tract already established by midgestation in the human fetus is consistent with the pattern previously demonstrated in adult experimental animals. A major finding of the study is that of the stellate cells at the junction of nucleus raphe pallidus and the arcuate nucleus at the ventral medullary surface, which project to the nucleus of the solitary tract, and could be homologous to chemosensitive serotonergic neurons at the midline ventral medullary surface of experimental animals. This connection between the ventral caudal raphe and the nucleus of the solitary tract may participate in chemoreception and central regulation of cardiorespiratory reflexes during human perinatal development; it is, therefore, relevant to the study of sudden infant death syndrome (SIDS).

Locations of neurons with respiratory-related activity in the ferret brainstem

Previous transneuronal tracing studies conducted in the ferret revealed that a large population of neurons that provides inputs to diaphragm and abdominal motoneurons is located in the ventral magnocellular portion of the medial medullary reticular formation. These observations raise the possibility that the neural substrate underlying respiratory rhythmogenesis may be different in the ferret than in other species in which this circuitry has been explored. In the present study, systematic tracking was conducted through the ferret medulla to map the locations of neurons with activity related to the contractions of respiratory muscles. As in the cat, rat, and rabbit, neurons with respiratory-related discharges were distributed either lateral or ventrolateral to the solitary nucleus (dorsal respiratory group) or in the vicinity of nucleus retroambigualis, nucleus ambiguus and the retrofacial nucleus (ventral respiratory group). Although the general organization of respiratory group neurons appeared to be similar in the ferret to that in other mammals, a difference was that few expiratory neurons were located rostrally in the ventral respiratory group. These data suggest that the ventral magnocellular medullary reticular formation is not essential for respiratory rhythm generation, at least during quiet breathing, but may participate in regulating the excitability of respiratory motoneurons or in coordinating the contractions of respiratory muscles during nonrespiratory responses (e.g. coughing or emesis).

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.

Expression of neuropeptide FF, prolactin-releasing peptide, and the receptor UHR1/GPR10 genes during embryogenesis in the rat.

Recently, several RF-amide peptides have been identified in mammals. These peptides have a similar C-terminal RF-motif and share some G-protein coupled receptors. Neuropeptide FF (NPFF) and prolactin-releasing peptide (PrRP) are expressed in the same brain areas in the adult rat and act both in prolactin release and cardiovascular regulation. Here, we characterized the embryonal expression from embryonal day 14 to postnatal day 0 of both peptide mRNAs and the mRNA distribution of UHR1/GPR10-like receptor by using in situ hybridization (ISH) and quantitative reverse transcriptase-polymerase chain reaction. NPFF mRNA was found in the spinal cord, caudal solitary tract nucleus, and surprisingly, in the medullary reticular formation. The only peripheral organs displaying NPFF mRNA expression were the lungs and the spleen. PrRP gene expression was seen in the caudal solitary tract nucleus, medullary reticular formation, pontine isthmus and liver, kidney, and testis. The receptor UHR1/GPR10 gene was expressed consistently in the medullary reticular formation and the adrenal gland but also transiently in several locations. All three genes showed weak but even ISH signal in the pituitary. These findings suggest different roles for the peptides during development and indicate that UHR1/GPR10-like receptor could also bind other ligands in addition to PrRP.

Cardiac effects of hypocretin-1 in nucleus ambiguus.

Although recent studies have reported hypocretin 1 (hcrt-1)-like-immunoreactivity (ir) within the region of the nucleus ambiguus (Amb) in the caudal brain stem, the function of hcrt-1 in the Amb on cardiovascular function is not known. Three series of experiments were done in male Wistar rats to investigate the effects of microinjections of hcrt-1 into Amb on heart rate (HR), mean arterial pressure (MAP), and the arterial baroreceptor reflex. In the first series, a detailed mapping of the distribution of hcrt-1- and hcrt-1 receptor (hcrtR-1)-like-ir was obtained of the Amb region. Although hcrt-1-like- and hcrtR-1-like-ir were found throughout the rostrocaudal extent of the Amb and adjacent ventrolateral medullary reticular formation, most of the hcrtR-1-like-ir was observed in the area just ventral to the compact formation of Amb, in the region of the external formation of the nucleus (Ambe). In the second series, the Amb region that contained hcrt-1 and hcrtR-1-ir was explored for sites that elicited changes in HR and MAP in urethane and alpha-chloralose-anesthetized rats. Microinjections of hcrt-1 (0.5-2.5 pmol) into the Ambe elicited a dose-related decrease in HR, with little or no direct change in MAP. The small decreases in MAP were found to be secondary to the HR changes. The largest bradycardia responses were elicited from sites in the Ambe. Administration (iv) of the muscarinic receptor antagonist atropine methyl bromide or ipsilateral vagotomy abolished the HR response, indicating that the HR response was due to activation of vagal cardiomotor neurons. In the final series, microinjections of hcrt-1 into the Ambe significantly potentiated the reflex bradycardia elicited by activation of the baroreflex as a result of the increased MAP after the intravenous injection of phenylephrine. These data suggest that hcrt-1 in the Ambe activates neuronal systems that alter the excitability of central circuits that reflexly control the circulation through the activation of vagal preganglionic cardioinhibitory neurons.

The gigantocellular depressor area revisited.

1. In studies conducted with Dr Donald Reis we described a functionally distinct region of the rat medullary reticular formation that we called the Gigantocellular Depressor Area (GiDA). The GiDA was defined as a region from which vasodepressor and sympathoinhibitory responses were evoked by nanoinjections of glutamate. We later showed that cells in the GiDA project to autonomic nuclei in the medulla, brainstem, and spinal cord, including the intermediolateral cell column. We also showed that kainic acid lesions of the GiDA induce hypertension and block the baroreceptor reflex evoked by electrical stimulation of the aortic depressor nerve. The present studies describe the effects of muscimol nanoinjections into the GiDA. 2. Nanoinjections of muscimol were made in the GiDA of anesthetized rats and changes in arterial pressure, heart rate, and responses to aortic depressor nerve stimulation were measured. 3. Bilateral nanoinjections of muscimol into the GiDA evoke an increase in arterial pressure and lead to fulminating hypertension. Unilateral injections of muscimol into the GiDA block the baroreflex response evoked by electrical stimulation of the ipsilateral aortic depressor nerve. However, these unilateral injections of muscimol into the GiDA evoked profound falls in arterial pressure to nearly spinal levels. In spite of this fall in blood pressure, heart rate also decreased significantly and there was not a compensatory tachycardia. Both the arterial pressure and baroreceptor responses required several hours to recover following the muscimol injections. 4. Although these data are consistent with the proposal that the GiDA is critical for the baroreflex. the opposing effects on blood pressure of unilateral and bilateral injections of muscimol are difficult to reconcile with ourcurrent models of central sympathetic regulation.

&lt;b&gt;Responses of the rat medullary reticular formation neurons to electrical stimulation of the sciatic nerve and &lt;/b&gt;&lt;b&gt;mechanical nociceptive stimulation of the skin &lt;/b&gt;

&lt;b&gt;Responses of the rat medullary reticular formation neurons to electrical stimulation of the sciatic nerve and &lt;/b&gt;&lt;b&gt;mechanical nociceptive stimulation of the skin &lt;/b&gt;

Cardiovascular and respiratory consequences of bilateral involvement of the medullary intermediate reticular formation in syringobulbia.

We studied five patients with clinical and radiological evidence of syringobulbia (SB) to determine whether the distribution of lesions in relationship to the cardiorespiratory control networks in the medullary intermediate reticular zone (IRt) correlates with the presence of abnormalities in autonomic cardiovascular and respiratory control in these patients. All patients underwent high resolution MRI to characterize the size, volume and distribution of the SB lesions, cardiovascular autonomic function testing and polysomnography. One patient with bilateral IRt involvement at both the rostral and caudal medulla had orthostatic hypotension (OH), absent HR(DB), abnormal Valsalva ratio, exaggerated fall of BP during phase II and absent phase IV during VM, and a dramatic fall of BP during head up tilt; this patient also had severe obstructive sleep apnea (OSA) and exhibited BP drops during each respiratory effort. A second patient, with bilateral IRt involvement restricted to the caudal medulla, had less severe cardiovascular autonomic dysfunction but also exhibited severe OSA. The other three patients had small SB cavities sparing the IRt and had sleep apnea but no autonomic dysfunction. Autonomic dysfunction could not be related to the size of the syrinx or the degree of atrophy in the cervical spinal cord in any of the five patients. Bilateral involvement of the IRt by SB produces cardiovascular autonomic failure and sleep apnea. In patients with more restricted lesions, autonomic and respiratory dysfunction may be dissociated. Clinico-radiological correlations using high resolution MRI assessment of medullary lesions can provide insight into the central organization of cardiovascular and respiratory control in humans.

Restricted distribution of galanin receptor 3 (GalR3) mRNA in the adult rat central nervous system

Recent molecular cloning studies have established the existence of a third rat galanin receptor subtype, GalR3, however its precise distribution in the mammalian central nervous system (CNS) is not well established. In the present study, we examined the regional and cellular distribution of GalR3 mRNA in the CNS of the rat by in situ hybridization. Our findings indicate that GALR3 mRNA expression in the rat brain is discrete and highly restricted, concentrated mainly in the preoptic/hypothalamic area. Within the hypothalamus, GalR3 expression was confined to the paraventricular, ventromedial and dorsomedial hypothalamic nuclei. In addition to these hypothalamic nuclei, GalR3 mRNA-expressing cells were observed in the medial septum/diagonal band of Broca complex, the bed nucleus of the stria terminalis, the medial amygdaloid nucleus, the periaqueductal gray, the lateral parabrachial nucleus, the dorsal raphe nucleus, the locus coeruleus, the medial medullary reticular formation and in one of the circumventricular organs, the subfornical organ. In the spinal cord, a faint but specific ISH signal was observed over the laminae I–II with a few moderately labeled cells distributed in laminae V and X. The neuroanatomical distribution of GalR3 suggests it might be involved in mediating documented effects of galanin on food intake, fluid homeostasis, cardiovascular function and nociception.

CART in the dorsal vagal complex: sources of immunoreactivity and effects on Fos expression and food intake

CART-peptide (CARTp) has been shown to suppress food intake, particularly when injected into the 4th ventricle of rats, and the presence of CART in nodose ganglia suggested a role in satiation. Based on retrograde tracing from the DVC combined with CART immunohistochemistry and supranodose vagotomy, we found that CART immunoreactivity in varicose fibers of the dorsal vagal complex originates from vagal afferents, sparse projections from the medullary reticular formation and the arcuate/retrochiasmatic nucleus of the hypothalamus, and most likely also from local CART neurons in the area postrema and NTS. In the nodose ganglia, 17% of neurons with projections to the stomach and 41% to the duodenum express CART-IR. CART-IR vagal afferents significantly contribute to the rich fiber plexus in mainly the commissural NTS and the adjacent area postrema. Injections of CARTp into the 4th ventricle strongly suppressed sucrose drinking and stimulated expression of c-Fos in the NTS. Injections of CARTp directly into various subnuclei of the NTS were less effective in suppressing food intake. The findings suggest that the critical site for CART’s suppression of food intake is not in the termination zone of CART-containing vagal afferents in the commissural NTS, and that CART release from vagal afferent terminals plays a minor role in satiation. The functional role of CART in vagal afferents and the site of food intake suppression by 4th ventricular CARTp remain to be determined.