Nucleus Reticularis Paragigantocellularis Research Articles

Chapter 16 Physiological functions of pontomedullary raphe and medial reticular neurons

This chapter focuses on the nociceptive modulatory role of neurons in the pontomedullary raphe magnus (RM) and the adjacent nucleus reticularis paragigantocellularis pars α (NRPGα) in the rat. This region is part of a system originally described by Oliveral and classically reported as the “endogenous analgesia system” by Fields and Basbaum. In the classic formulation, neurons in the midbrain periaqueductal gray (PAG) were thought to suppress pain transmission via a monosynaptic relay with RM neurons, including serotonergic cells, that project to the spinal dorsal horn. Since the original description of descending pain modulation, the understanding of these pathways has grown in several ways. First, it is know that the PAG-RM-dorsal horn pathway is only one of several pathways that can affect spinal and trigeminal nociceptive transmission. Other brainstem areas, including the parabrachial nuclei the lateral reticular nucleus, and the A5 and A7 catecholaminergic nuclei, as well as forebrain areas, such as the amygdala and medial preoptic nucleus are now thought to play important roles in nociceptive modulation. Second, the pharmacology of pain modulation, once thought to center on endogenous opioids, serotonin and norepinephrine, has been complicated by the discovery of a multitude of peptides and amino acid transmitters contained in both pain modulatory and pain transmission neurons.

Effects of isoflurane concentration on the activity of pontomedullary raphe and medial reticular neurons in the rat

Neurons in the pontomedullary raphe magnus (RM) and adjacent nucleus reticularis paragigantocellularis pars α (NRPGα) are thought to participate in the modulation of spinal nociceptive transmission. In order to determine whether these cells also contribute to the suppression of nocifensive reflexes produced by general anesthetics, the spontaneous activity of RM/NRPGα cells was recorded in rats anesthetized with isoflurane (IF) at several steady state concentrations, corresponding to depths which are below, equal to, or above the threshold for blocking the motor response to noxious stimuli (minimum alveolar concentration, MAC). Neurons were classified by their spontaneous activity patterns and their responses to noxious stimulation as OFF, ON, REGULAR or NEUTRAL cells. After cell classification, unit activity, arterial blood pressure, heart rate, and EEG activity were simultaneously recorded, in the absence of somatic stimulation, for 1 h at each of two or three concentrations of IF. The concentrations tested were low (1.05–1.25%), medium (1.30–1.45%) and high (1.70–1.90%). ON, OFF and some NEUTRAL cells exhibited alternating periods of inactivity and activity when recorded during periods of low and medium anesthetic concentrations. At high steady state anesthetic concentrations, the mean discharge of most OFF, ON and NEUTRAL cells decreased by greater than 25% from their mean discharge rate at the low concentration. REGULAR cells maintained a uniform firing rate at all steady state anesthetic concentrations studied. Since high concentrations of IF do not activate OFF cells, the putative inhibitory output neuron of the RM/NRPGα, it is unlikely that the activity of RM/NRPGα neurons contributes to the suppression of nocifensive movement by the general anesthetic, IF.

Efferent connections from the external cuneate nucleus to the medulla oblongata in the gerbil

The present study revealed the efferent projections from the external cuneate nucleus (ECN) to various medullary nuclei in the gerbl as demonstrated in fresh living brainstem slices by using in vitro anterogradely tracing with the dextran-tetramethyl-rhodamine-biotin. The tracer-labelled ECN axon terminals were observed (1) in most of the vital autonomic-related nuclei: the nucleus solitary tractus, nucleus ambiguus, rostroventrolateral reticular nucleus and C 2 adrenergic area, (2) in the reticular formation: the medullary, parvocellular, intermediate, gigantocellular, dorsal paragigantocellular and lateral paragigantocellular reticular nuclei and medullary linear nucleus, and (3) in sensory nuclei: the cuneate nucleus, spinal trigeminal nuclei caudalis and interpolaris, paratrigeminal nucleus, medial and spinal vestibular nuclei, inferior olive and prepositus hypoglossal nucleus. These new findings are discussed in relation to possible roles of the ECN in cardiovascular, respiratory and sensorimotor controls.

Antinociceptive mechanism of the aconitine alkaloids mesaconitine and benzoylmesaconine.

We explored the possible role of the specific regions in the brain stem on the antinociceptive actions of mesaconitine (MA) and benzoylmesaconine (BM) by the microinjection of MA and BM into nucleus reticularis paragigantocellularis (NRPG), nucleus raphe magnus (NRM), and periaqueductal gray (PAG). MA microinjected into NRPG, NRM, or PAG elicited a dose-dependent antinociceptive action, whereas BM injected into NRM or PAG elicited a dose-dependent antinociceptive action but not in NRPG. The NRM appeared to be the most sensitive region among the three tested locations.

Interacting brain stem components of opiate-activated, descending, pain-inhibitory systems

This is a review of research aimed at elucidating how various opiate analgesia substrates in rat brain stem interact with one another to bring about opiate analgesia. The three substrates studied are the midbrain periaqueductal grey (PAG), the bulbar nucleus raphe magnus (RM), and the bulbar nucleus reticularis paragigantocellularis (PGC). The methods used in the reviewed studies are unique in that behavioral and neuronal responses are assessed in consequence of nanoinjecting opiates (met-enkephalin) into subset pairs of these structures. Responses to single and conjoint injections are compared. Effects on neuronal and behavioral responses in consequence of disruption of these structures with tetracaine block are also discussed. It is seen that PGC cannot serve as an opiate analgesia substrate if the functional integrity PAG is impaired. However PAG does not depend on PGC's functional integrity.

Localization of the antinociceptive and antianalgesic effects of neurotensin within the rostral ventromedial medulla.

Triple microinjections of neurotensin (10 nmol each), which occupied a large volume of tissue within the nucleus reticularis gigantocellularis (Gi), produced an inhibition of the tail-flick reflex in awake rats. This effect was less than that previously observed by a single injection (10 nmol) into the nucleus raphe magnus (RMg) (see ref. [25]). Bilateral injections of neurotensin (10 nmol each) into the nucleus reticularis paragigantocellularis lateralis (LPGi) had no effect. The neurotensin antagonist [D-Trp11]-neurotensin (3 pmol) was previously found to enhance morphine, but not beta-endorphin antinociception from the periaqueductal gray (PAG) when injected into the RMg. A similar enhancement of morphine, but not beta-endorphin antinociception from the PAG was observed in the current study by [D-Trp11]-neurotensin injections into the bilateral LPGi, bilateral Gi, or medial Gi. These data suggest that neurotensinergic projections from the PAG function in an antianalgesic manner throughout the RVM during morphine, but not beta-endorphin antinociception. The antinociceptive effect of neurotensin, on the other hand, is more localized.

Neurocircuitry of illness-induced hyperalgesia

We have previously demonstrated that illness-inducing agents such as lithium chloride (LiCl) and the bacterial cell wall endotoxin lipopolysaccharide (LPS) produce hyperalgesia on diverse pain measures. The present series of studies attempted to identify the neurocircuitry mediating these effects. These studies have demonstrated that illness-inducing agents produce hyperalgesia by activating: (a) peripheral nerves rather than by generating a blood-borne mediator (Expt. 1); (b) vagal afferents, specifically afferents within the hepatic branch of the vagus (Expt. 2); (c) as yet unidentified brain site(s) rostral to the mid-mesencephalon (Expt. 6); (d) a centrifugal pathway that arises from the nucleus raphe magnus, and not from the adjacent nucleus reticularis paragigantocellularis pars alpha (Expts. 4 and 5); (e) a centrifugal pathway in the dorsolateral funiculus of the spinal cord (Expt. 3); and (f) the same centrifugal pathways for diverse illness inducing agents (Expts. 3, 7 and 8). These data call for the re-evaluation of a number of assumptions inherent in previous studies of hyperalgesia.

Opioid peptide gene expression in the nucleus trctus solitarius of rat brain and increases induced by unilateral cervical vagotomy: Implications for role of opioid neurons in respiratory control mechanisms

Neurons expressing messenger RNA encoding the opioid peptide precursors, preproenkephalin and preprodynorphin were localized in the medulla oblongata of the rat by in situ hybridization of specific DNA oligonucleotide probes. Neurons containing preproenkephalin messenger RNA were found throughout the medullary reticular formation in the gigantocellular and paragigantocellular reticular nuclei, the parvicellular and lateral reticular nuclei; commissural, medial and ventrolateral subnuclei in the nucleus tractus solitarius and the nucleus of the spinal trigeminal tract. Labelled cells were also concentrated in the more medial regions of the area postrema. In contrast, neurons containing preprodynorphin messenger RNA had a more restricted distribution and were detected in the commissural and ventrolateral nucleus tractus solitarius and nucleus of the spinal trigeminal tract, especially in the more dorsal regions. Expression of preproenkephalin and preprodynorphin messenger RNA was also examined in the dorsal vagal complex of rats that had undergone a unilateral nodose ganglionectomy or cervical vagotomy. Twenty-four hours after both cervical vagotomy and nodose ganglionectomy, there was a specific 1.5–2-fold elevation in preproenkephalin and preprodynorphin messenger RNA levels in the ventrolateral subnucleus of the contralateral nucleus tractus solitarius relative to levels in the ipsilateral nucleus tractus solitarius and in the nucleus tractus solitarius of sham-operated animals. Previous immunohistochemical studies demonstrating the co-localization of enkephalin and dynorphin in the ventrolateral nucleus tractus solitarius suggest that these changes occurred in the same population of neurons. In light of the suggested role of the ventrolateral nucleus tractus solitarius as a central respiratory centre and the activation of the intact pulmonary afferents that innervate this area following a unilateral vagotomy (which increases inspiration volume and expiratory time by affecting the Hering-Breuer reflex), our results suggest a specific involvement of enkephalin- and dynorphin-containing neurons in the ventrolateral nucleus tractus solitarius in central respiratory control mechanisms.

CNS cell groups projecting to pancreatic parasympathetic preganglionic neurons

The CNS cell groups that project to the pancreatic parasympathetic preganglionic neurons were identified by the viral retrograde transneuronal labeling method. Pseudorabies virus (PRV) was injected into the pancreas of C8 spinal rats and after 6 days survival, the animals were perfused and their brains processed for immunohistochemical detection of PRV. Parasympathetic preganglionic neurons of the dorsal vagal nucleus were retrogradely labeled with PRV. Several CNS cell groups consistently contained transneuronally labeled neurons. In the medulla oblongata, labeled neurons were found in the nucleus tractus solitarius, area postrema, paratrigeminal nucleus, lateral paragigantocellular reticular nucleus, raphe pallidus and obscurus nuclei, C3 region and scattered cells in the ventral medullary reticular formation. In the pons, the A5 cell group, Barrington's nucleus and the subcoeruleus region contained labeled neurons. Only an occasional labeled cell was identified in the parabrachial nucleus. In the midbrain, almost no labeling was found except for an occasional neuron in the central gray matter. In the diencephalon, labeling was found in the paraventricular hypothalamic nucleus (PVN) as well as in the lateral hypothalamic nucleus at two levels (one at the level of the PVN and the other at the level of the subthalamic nucleus). in addition, the perifornical and dorsal hypothalamic nuclei contained labeled neurons. A few cells were found in the peripheral part of the dorsomedial hypothalamic nucleus. No labeling was seen in the ventromedial hypothalamic nucleus. In the telencephalon, the central amygdaloid nucleus and the bed nucleus of the stria terminalis were labeled.

CNS innervation of airway-related parasympathetic preganglionic neurons: a transneuronal labeling study using pseudorabies virus

The CNS cell groups that innervate the tracheal parasympathetic preganglionic neurons were identified by the viral retrograde transneuronal labeling method. Pseudorabies virus (PRV) was injected into the tracheal wall of C8 spinal rats and after 4 days survival, brain tissue sections from these animals were processed for immunohistochemical detection of PRV. Retrogradely labeled parasympathetic preganglionic neurons were seen in three sites in the medulla: the compact portion of the nucleus ambiguus, the area ventral to the nucleus ambiguus, and the rostralmost portion of the medial nucleus tractus solitarius (NTS); this labeling pattern correlated well with the retrograde cell body labeling seen following cholera toxin ß-subunit injections in the tracheal wall. PRV transneuronally labeled neurons were found throughout the CNS with the most abundant labeling concentrated in the ventral medulla oblongata. Labeled neurons were identified along the ventral medullary surface, and in nearby areas including the parapyramidal, retrotrapezoid, gigantocellular and lateral paragigantocellular reticular nuclei as well as the caudal raphe nuclei (raphe pallidus, obscurus, and magnus). Serotonin (5-HT) neurons of the caudal raphe complex (B1–B3 cell groups) and ventromedial medulla were labeled as well as a few C1 adrenergic neurons. The A5 cell group was the major noradrenergic area labeled although a small number of locus coeruleus neurons were also labeled. Several NTS regions contained labeled cells including the commissural, intermediate, medial, central, ventral, and ventrolateral subnuclei. PRV infected neurons were present in the Kölliker-Fuse and Barrington's nuclei. In the rostral mesencephalon, the precommissural nucleus of the dorsal periventricular gray matter was labeled. Labeling was present in the dorsal, lateral and paraventricular hypothalamic nuclei. In summary, the airway parasympathetic preganglionic neurons are innervated predominantly by a network of lower brainstem neurons that lie in the same regions known to be involved in respiratory and cardiovascular regulation. These findings are discussed in relationship to some of the potential CNS mechanisms that may be operative in airway disorders as well as potentially involved in certain fatal respiratory conditions such as Ondine's curse and sudden infant death syndrome (SIDS).

Studies of brain structures involved in diffuse noxious inhibitory controls in the rat: the rostral ventromedial medulla.

1. Previous electrophysiological, pharmacological and anatomical evidence had suggested a possible participation of rostral ventromedial medulla (RVM) in the supraspinal part of the loop underlying diffuse noxious inhibitory controls (DNICs). In order to test this hypothesis, two experimental series were performed during which DNICs were compared in control sham-operated rats and rats with lesions of the RVM and of an adjacent candidate for such a role, the nucleus gigantocellularis reticularis (Gi). 2. In the first experimental series, lesions were induced, in anaesthetized animals, by injections of quinolinic acid (0.3-0.8 microliter of a 360 nmol/microliter solution) into the RVM or Gi. In the control animals (n = 10), the vehicle alone (artificial cerebrospinal fluid) was injected. Histological lesion reconstructions were performed after each electrophysiological experiment. Three groups of animals were considered: in the first group (n = 5), the lesion was centered on the RVM, including the two caudal thirds of nucleus raphe magnus (NRM) and adjacent reticular areas; in the second group (n = 5), the lesions extended more rostrally and involved the rostral pole of NRM; in the third group (n = 5), the lesion extended more laterally and dorsally and included nucleus reticularis gigantocellularis pars alpha (GiA), nucleus reticularis paragigantocellularis lateralis (LPGi) and the Gi. In each case, all the neuronal cell bodies within the lesioned area were destroyed. 3. In the second experimental series, electrolytic lesions of the total rostrocaudal extent of the NRM (n = 5) were induced, in anesthetized animals, by passing cathodal current (5 mA, 8 s). In the control animals (n = 5), the electrode was lowered but current was not applied. 4. One week after lesioning, the animals were anaesthetized, paralysed, artificially ventilated and recordings were made from convergent neurones in trigeminal nucleus caudalis. These neurones gave responses due to activation of A and C fibres when percutaneous electrical stimuli were applied to their receptive fields. DNICs were triggered by immersion of each paw in a 50 degrees C water-bath. Both the general properties of the convergent neurones and the inhibitions of the C fibre-evoked responses produced by these heterotopic noxious stimuli were compared in the different groups of animals. 5. The sizes of receptive field, spontaneous activities, thresholds for C fibre-evoked responses and responses to C fibre activation were not different in the control and lesioned animals. The percentage inhibitions of the C fibre-evoked responses both during and in the 44s following the conditioning periods were also very similar in the different groups of animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Histamine immunoreactive neurons in the brain stem of the rabbit

Distribution of histamine-like immunoreactive (HA-LI) neurons in the rabbit brain stem was demonstrated by histamine antiserum. A number of HA-LI cell bodies were localized in the tuberomammillary nucleus of the posterior hypothalamus. A dense to moderate amount of HA-LI fibers was found distributed in the raphe nuclei, the inferior olive, the nucleus of the solitary tract, vestibular nuclei, and the paragigantocellular reticular nucleus in the medulla oblongata, and the parabrachial nuclei, the Klliker-Fuse nucleus, the pontine nuclei, and the locus coeruleus in the pons. HA-LI axons synapsed on dendrites of neurons in the nucleus of the solitary tract. This evidence suggests that histaminergic neurons control neuronal activity through synaptic transmission in the lower brain stem.

Lesions of the nucleus paragigantocellularis: effects on mating behavior in male rats

We evaluated the effects of bilateral radio-frequency lesions of the paragigantocellular (PGi) reticular nucleus in the ventral medulla on male rat copulatory behavior. In Experiment 1, sexually naive male rats with such lesions were more likely than sham-operated controls to copulate to ejaculation during their first exposure to an estrous female. Additionally, among the rats that copulated to ejaculation, those with lesions demonstrated a reduction in mount frequency (MF), intromission frequency (IF), and ejaculation latency (EL), and an increase in copulatory efficiency (CE). In Expt. 2, sexually experienced male rats were allowed to sexual exhaustion. Males with PGi lesions showed an increased latency to sexual exhaustion and an increased number of ejaculations prior to exhaustion. Additionally, rats with PGi lesions displayed reductions in IF, EL, and post-ejaculatory interval (PEI) as they approached sexual exhaustion. Our results provide further evidence that the PGi is a supraspinal locus of descending inhibitory influence on spinal nuclei mediating ejaculatory reflexes in the male rat.

Localization of the central antinociceptive effects of diclofenac in the rat

The ethacrynic acid-induced writhing response (WR) in the rat was studied after microinjections of diclofenac 0.1 ng−1 μg/0.5 μl (0.32 pmol to 3.2 nmol) into several brain regions involved in control of nociceptive behavior. The WR was inhibited after injections into the periaqueductal grey matter (PAG), ventromedial thalamus (VM), medial preoptic area (MPA) and the nucleus raphe magnus (NRM). Morphine 50 ng/0.5 μl (0.16 nmol) was used as a positive control and vehicle injections were performed as negative reference. After diclofenac, there was a dose-dependent reduction of the WR with a threshold dose of approximately 1–10 ng in all brain areas studied except the nucleus reticularis paragigantocellularis interna (NRPGi). Naloxone 50 ng/0.5 μl (0.15 nmol) administered into the same site 30 min after diclofenac injection, antagonized the diclofenac-induced inhibition of the WR almost completely in PAG and VM. Previous results demonstrate a central, naloxone-reversible component in the analgetic action of diclofenac. A qualitatively similar, centrally induced inhibition of the WR may be elicited after injections into PAG, VM and NRM. Thus, in addition to its peripheral mechanism of action, the non-steroidal anti-inflanmatory drug, diclofenac, has a central mechanism of action directly or indirectly involves a central opioid component.

The origins of supraspinal projections to the cervical and lumbar spinal cord at different stages of development in the gray short-tailed Brazilian opossum, Monodelphis domestica

We have used the retrograde transport of Fast blue (FB) to study the origins of supraspinal projections to the lumbar and cervical spinal cord at different stages of development in the Brazilian, short-tailed opossum, Monodelphis domestica. Monodelphis was chosen for study because its young are born in a very immature state, 14–15 days after copulation, making it possible to manipulate its nervous system in an embryonic state without intra-uterine surgery. When injections of FB were made into the lumbar cord at postnatal day (PD) 1, neurons were labeled within several areas of the reticular formation (the retroambiguus nucleus, the ventral and dorsal reticular nuclei of the medulla, the gigantocellular reticular nucleus, the lateral paragigantocellular reticular nucleus, and the pontine reticular nucleus), the presumptive coeruleus complex, and the lateral vestibular nucleus. In many cases, labeled neurons were also found within the caudal raphe and the presumptive interstitial nucleus of the medial longitudinal fasciculus. The results of immunocytochemical studies provided evidence for catecholaminergic and serotoninergic neurons in the brainstem at PD1 and for axons of both phenotypes in the spinal cord. By PD3, labeled neurons were found within the ventral gigantocellular and ventral pontine nuclei of the reticular formation, the spinal trigeminal nucleus, and the presumptive paraventricular nucleus of the hypothalamus. When injections were made at PD4, neurons were also labeled within the medial and inferior vestibular nuclei, the red nucleus, the mesencephalic nucleus of the trigeminal nerve, the presumptive nucleus of Edinger-Westphal and the lateral hypothalamus. By at least PD7, the pattern of supraspinal labeling was similar to that obtained at older ages and in the adult animal. When FB was injected into the cervical cord at PD1, neurons were labeled in all of the areas labeled by lumbar injections at the same age and in larger numbers. In addition, labeled neurons were found within the ventral gigantocellular and spinal trigeminal nuclei. When cervical injections were made at PD15, labeled neurons were found within the deep cerebellar nuclei and amygdala and by PD17 they were also present within the superior colliculus and cerebral cortex. In some cases, cortical labeling was present outside the areas labeled by comparable injections in adult animals. Our results indicate that: (1) restricted areas of the brainstem innervate the spinal cord at birth in Monodelphis and some of the neurons which contribute to that innervation are monoaminergic, (2) several areas of the brain do not project to the spinal cord until well after birth and (3) the development of descending spinal pathways occurs asynchronously and according to a predictable sequence.

Behavioral and trigeminal neuronal effects of rat brainstem-nanoinjected opiates

Single injections of Met-enkephalin (ME; 27 rats) and artificial cerebrospinal fluid (ACF; 9 rats) in nucleus reticularis paragigantocellularis (PGC) and periaqueductal gray (PAG), and simultaneous conjoint PAG + PGC injections were made, and effects on facial responsiveness and caudal-trigeminal nuclear neuronal activity studied. It was found that all ME injections depressed the evoked excitatory neuronal and behavioral responses to noxious stimulation. Conjoint injections had apparently additive effects in comparison to single injection effects. Neither conjoint nor single injections had systematic effects on spontaneous neuronal activity. The ACF had no effects on any neuronal or behavioral activity.

Immunohistochemical study of the development of serotoninergic neurons in the brain of the brook trout Salvelinus fontinalis.

Serotonin is believed to play an important role in the neuronal development of various invertebrates and mammals, but only one study has yet investigated the development of serotoninergic neurons in the brain of a teleost. In the present study, we investigate the development of serotoninergic neurons in the brain of the brook trout, Salvelinus fontinalis, by immunohistochemistry, from fertilisation to the resorption of the yolk sac and in juveniles for reference. Maintaining trout embryos and larvae in 9L:15D or in complete darkness made no difference in the appearance and distribution of serotonin immunoreactive (5-HTir) neurons. On day 56, the first 5-HTir perikarya, indicative of the primordia of the nuclei raphe medialis/dorsalis, have stained in the presumptive isthmus region. At hatching time (days 95-115), all the 5-HTir nuclei reported in the juvenile are present, except for the population observed in the lobus inferior hypothalami. We observed that the nucleus recessus lateralis stained on day 58, the raphe caudal nucleus on day 60, the nuclei raphe pallidus and obscurus on day 65, the area praetectalis on day 80, and the nucleus recessus posterioris and the anterior group of the nucleus recessus lateralis on day 92. At the complete resorption of the yolk sac (days 175-190), the nucleus reticularis paragigantocellularis, the nuclei raphe pallidus and obscurus and the caudal raphe of the brainstem are very weakly immunoreactive, and in juveniles, only one caudal immunoreactive nucleus is still present. A comparison of our result with those previously reported in the three-spined stickleback, Gasterosteus aculeatus, suggest a similar distribution of 5-HTir neurons in the brain of both species but also reveal species differences in the sequence of appearance of 5HT immunoreactivity in the different neuronal populations.

Organization of the cerebellum in the pigeon (Columba livia): II. Projections of the cerebellar nuclei

The projections of the deep cerebellar nuclei in the pigeon have been delineated using autoradiographic and histochemical (WGA-HRP) tracing techniques. A medial (CbM) and lateral (CbL) cerebellar nucleus are recognized and CbM may be further partitioned into internal, intermediate, and intercalate divisions. As in mammals, most extracerebellar projections of CbM travel in the fasciculus uncinatus (FU); the rest travel with those of CbL in the brachium conjunctivum (BC). In the pigeon, both of these pathways are bilaterally but primarily contralaterally projecting systems. FU is a predominantly descending tract, with terminations within (1) the vestibular complex, (2) a column of contiguous medial reticular nuclei from pontine to caudal medullary levels; (3) the plexus of Horsley portion of the parvicellular reticular formation, continuing through the nucleus centralis medullae oblongatae, pars dorsalis, into intermediate layer VII of the cervical spinal cord, down to cervical segment 8-9; (4) the lateral reticular nucleus and the paragigantocellular reticular nucleus; (5) the dorsal lamella of the inferior olive. Rostrally FU terminals are found in the locus ceruleus and dorsal subcerulean nucleus. Minimal FU projections are also seen to the motor trigeminal nucleus and the subnucleus oralis of the descending trigeminal system. A small projection from the intercalate division of CbM travels in BC and projects upon the midbrain central grey, the intercollicular nucleus, the lateral tectal periventricular grey, the stratum cellulare externum and, sparsely, upon the dorsolateral thalamus. The bulk of BC originates from the lateral cerebellar nucleus and consists of a massive ascending and a small descending branch. The ascending system projects upon the red nucleus and the dorsally adjacent interstitial nucleus of Cajal and midbrain central grey, the prerubral fields continuing into the stratum cellulare externum, the nucleus intercalatus thalami, the ventrolateral thalamic nucleus, the medial spiriform nucleus, the nucleus principalis precommissuralis, the nucleus of the basal optic root, the nucleus geniculatus lateralis pars ventralis, the dorsolateral thalamus, including the dorsal intermediate posterior, and the dorsolateral intermediate and anterior nuclei. BC also contains axons from the infracerebellar nucleus, which projects upon the trochlear and the oculomotor nuclei. The descending branch of BC distributes to the papilioform nucleus, the medial pontine nucleus, the gigantocellular and paramedian reticular nuclei, and, minimally, the rostral portions of the medial column and ventral lamella of the inferior olive. Taken in conjunction with data on amphibia and reptiles the present findings suggest that the fundamental ground plan of vertebrate cerebellar organization involves a medial and lateral cerebellar nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of single nanoinjections of met-enkephalin in the minimally anesthetized rat brainstem on trigeminal nuclear neurons: differential effects on spontaneous versus evoked activity and noci-evoked versus innocuously-evoked responses

Two separate studies were done on two sets of rats (33 rats, 101 cells in Expt. 1; 16 rats, 25 cells in Expt. 2). In the first study trigeminal nuclear neurons were categorized by adequate stimulus and receptive field. A total of 43.6% responded to light touch and noxious (pinch and heat) stimulation; 27.7% responded only to noxious pinch and/or heat; 8.9% responded exclusively to innocuous touch, and the remainder were non-responsive. Ninety percent of the responsive cells showed increased discharge rates in response to noxious stimulation. In the second study, after characterization of response properties, single nanoinjections of Met-enkephalin (ME) were separately made into midbrain periaqueductal gray (PAG) and nucleus reticularis paragigantocellularis (PGC). The effects of ME on spontaneous (SD) and evoked (ED) discharge were assessed, and then in 8 cells, the effects were repeated and successfully challenged with naloxone. The major findings were: (1) ME applied either to PAG or PGC causes naloxone-reversible reduction of noci-evoked ED with no effect on SD; and (2) the responses of neurons to innocuous light touch were unaffected by ME.

GABAergic circuitry in the rostral ventral medulla of the rat and its relationship to descending antinociceptive controls

This study used postembedding immunocytochemistry to examine the organization of GABA-immunoreactive synapse in the rostral ventral medulla (RVM) of the rat. To determine whether the outflow neurons of the RVM are under GABAergic control, we examined the distribution of GABA-immunoreactive synapses upon bulbospinal projection neurons that were labelled by retrograde transport of wheatgerm agglutinin-HRP from the cervical spinal cord. To study the possible convergence of GABAergic and periaqueductal gray (PAG) synaptic inputs to RVM neurons, we also made lesions in the PAG and examined the relationship between degenerating PAG axons and GABA-immunoreactive terminals. Approximately 45% of all synapses in the RVM, which includes the midline nucleus raphe magnus and the nucleus reticularis paragigantocellularis lateralis, were GABA-immunoreactive. The vast majority of GABA-immunoreactive terminals contained round, clear, and pleomorphic vesicles and made symmetrical axodendritic synapses; axoaxonic synapses were not found. Almost 50% of the retrogradely labeled dendrites in the NRM were postsynaptic to GABA-immunoreactive terminals. Several examples of convergence of degenerating PAG terminals and GABAergic terminals onto the same unlabelled dendrite were also found. These data indicate that the projection neurons of the RVM are under profound GABAergic inhibitory control. The results are discussed with regard to the hypothesis that the analgesic action of narcotics and electrical stimulation of the midbrain PAG involves the regulation of tonic GABAergic inhibitory controls that are exerted upon spinally-projecting neurons of the nucleus raphe magnus.