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Human reticular formation: cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei and some cytochemical comparisons to forebrain cholinergic neurons.

Choline acetyltransferase immunohistochemistry showed that the human rostral brainstem contained cholinergic neurons in the oculomotor, trochlear, and parabigeminal nuclei as well as within the reticular formation. The cholinergic neurons of the reticular formation were the most numerous and formed two intersecting constellations. One of these, designated Ch5, reached its peak density within the compact pedunculopontine nucleus but also extended into the regions through which the superior cerebellar peduncle and central tegmental tract course. The second constellation, designated Ch6, was centered around the laterodorsal tegmental nucleus and spread into the central gray and medial longitudinal fasciculus. There was considerable transmitter-related heterogeneity within the regions containing Ch5 and Ch6. In particular, Ch6 neurons were intermingled with catecholaminergic neurons belonging to the locus coeruleus complex. The lack of confinement within specifiable cytoarchitectonic boundaries and the transmitter heterogeneity justified the transmitter-specific Ch5 and Ch6 nomenclature for these two groups of cholinergic neurons. The cholinergic neurons in the nucleus basalis (Ch4) and those of the Ch5-Ch6 complex were both characterized by perikaryal heteromorphism and isodendritic arborizations. In addition to choline acetyltransferase, the cell bodies in both complexes also had high levels of acetylcholinesterase activity and nonphosphorylated neurofilament protein. However, there were also marked differences in cytochemical signature. For example, the Ch5-Ch6 neurons had high levels of NADPHd activity, whereas Ch4 neurons did not. On the other hand, the Ch4 neurons had high levels of NGF receptor protein, whereas those of Ch5-Ch6 did not. On the basis of animal experiments, it can be assumed that the Ch5 and Ch6 neurons provide the major cholinergic innervation of the human thalamus and that they participate in the neural circuitry of the reticular activating, limbic, and perhaps also extrapyramidal systems.

Adult↗

Glycine-immunoreactive neurones in the cat brain stem reticular formation.

Using a specific glycine antiserum, we determined the localization of glycinergic neurones and fibres in the cat brain stem reticular formation. We visualized a large number of glycine-immunoreactive cell bodies and fibres in the medullary reticularis gigantocellularis, magnocellularis, paragigantocellularis lateralis and parvocellularis nuclei. The pontis oralis and caudalis and the raphe magnus nuclei also contained a large number of glycine-immunoreactive fibres but fewer neurones. Using a double staining method, we further observed glycine-immunoreactive boutons over (1) noradrenergic neurones in the locus coeruleus complex and the ventrolateral and dorsomedial medulla, (2) serotoninergic neurones in and outside the raphe nuclei and (3) cholinergic neurones in the pedunculopontine and laterodorsal tegmental nuclei. These results suggest that glycinergic neurones in the reticular formation may be involved in aspects of paradoxical sleep, including the general muscle atonia seen during this sleep state.

Animals↗

The effects of nanoliter ejections of lidocaine into the pontomedullary reticular formation on cortically induced rhythmical jaw movements in the guinea pig.

In the ketamine/urethane anesthetized guinea pig, electromyographic (EMG) responses of the anterior digastric muscle were studied when loci within the lower brainstem were microejected with lidocaine (2%) during rhythmical jaw movements (RJMs) evoked by repetitive electrical stimulation of the masticatory area of the cortex. The area investigated was between the trigeminal motor nucleus (Mot V) and the rostral pole of the inferior olive. Microejections of lidocaine, contralateral to the cortical stimulus site, into the ventral-medial portion of Mot V where digastric motoneurons are known to be located, resulted in reduction or complete abolishment of the digastric EMG activity ipsilateral to the ejection with no effective change in mean cycle duration (CD) or mean percent normalized integrated amplitude of the contralateral digastric EMG. Microejections of lidocaine, contralateral to the cortical stimulus site, into the ponto-medullary reticular formation in areas that included portions of the caudal nucleus pontis caudalis (PnC), nucleus gigantocellularis (GC), medial nucleus parvocellularis (PCRt), and dorsal paragigantocellularis (dPGC), in most cases produced a bilateral reduction in the mean normalized integrated amplitude and a bilateral increase in the mean cycle duration. In these sites, the bilateral increase in mean cycle duration of digastric EMG bursts was also associated with a significant increase of coefficient of variation in CD. In many cases, microejection of lidocaine completely abolished rhythmical digastric activity, bilaterally. HRP injections into Mot V were performed to determine the locations of trigeminal premotoneurons and their relationship to effective lidocaine sites for rhythmical jaw movement suppression. Retrogradely labeled cells were found mainly in the mesencephalic nucleus of V; trigeminal principal and spinal V sensory nuclei, bilaterally; and within the intermediate and lateral regions of reticular formation, bilaterally. No labeling was found in the medial reticular formation, including the nucleus gigantocellularis and dorsal paragigantocellularis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Effect of opioid peptides, morphine and electroacupuncture on the neuronal activity of the sensorimotor cortex and brain stem reticular formation].

Experiments were made on unanesthetized rabbits and cats to examine the neuronal response (the sensomotor cortex, mesencephalic reticular formation, giant cell reticular nucleus of the medulla oblongata) to microapplications of enkephalins, endorphins, morphine, and electroacupuncture. Opiate peptides, morphine, and electroacupuncture produced similar, unidirectional changes in both spontaneous and nociceptive-stimulated neuronal activity. Naloxone removed these reactions. It is assumed that in the brain structures under study, the electroacupuncture effects are mediated by opiate receptors and are linked with enkephalin and endorphin release.

Acupuncture Therapy↗

Trigeminal premotor neurons in the bulbar parvocellular reticular formation participating in induction of rhythmical activity of trigeminal motoneurons by repetitive stimulation of the cerebral cortex in the guinea pig.

1. Single-unit activity was recorded from neurons in the bulbar parvocellular reticular formation (PCRF) dorsal and dorsolateral to the gigantocellular reticular nucleus near its caudal boundary, and the roles of these reticular neurons in induction of rhythmical activity of trigeminal motoneurons by repetitive stimulation of the cerebral cortex (the cortical masticatory area, CMA) were studied in the paralyzed guinea pig anesthetized with urethan or with ketamine and chlorpromazine. 2. One hundred nine PCRF neurons were activated antidromically by microstimulation in either the masseter (MA) or anterior digastric (AD) motoneuron pool in the ipsilateral trigeminal motor nucleus, and orthodromically by stimulation in the contralateral CMA. Repetitive CMA stimulation induced rhythmical burst activity in these PCRF neurons in association with the rhythmical field potential in the contralateral AD motoneuron pool induced by the same CMA stimulation. The burst was synchronous with the rhythmical AD field potential in 81 neurons, 44 and 37 of which responded antidromically to stimulation in the MA and AD motoneuron pools, respectively. The remaining 28 neurons antidromically responded to stimulation in the MA motoneuron pool, and their burst corresponded in time with the period between successive AD field potentials. 3. Spike-triggered averaging of the intracellular potentials of MA and AD motoneurons (MNs) by simultaneously recorded spontaneous spikes of the PCRF neurons, which showed rhythmical burst responses during the jaw-opening phase to repetitive CMA stimulation, revealed a monosynaptic inhibitory postsynaptic potential in MA.MNs in 12 of 34 tested pairs and a monosynaptic excitatory postsynaptic potential (EPSP) in AD.MNs in 14 of 26 tested pairs. An EPSP was also found in MA.MNs after a monosynaptic latency from triggering spikes in 11 of 37 tested PCRF neurons that showed burst activity during the jaw-closing phase. 4. We conclude that both excitatory and inhibitory premotor neurons projecting to MA.MNs as well as excitatory premotor neurons projecting to AD.MNs are located in the PCRF, and that these premotor neurons relay the output of the central rhythm generator for rhythmical jaw movements in the medial bulbar reticular formation to trigeminal motoneurons, and thus participate in induction of rhythmical activities of trigeminal motoneurons by repetitive CMA stimulation.

Animals↗

Bilateral sensory neglect following midsagittal reticular formation lesions in cats.

We have observed that midsagittal reticular formation lesions in cats produce bilateral deficits in attention to and localization of various sensory modalities. To correlate these changes with previously reported changes following lesions in other areas of the brain, we propose the existence of two interdependent inhibitory pathways which originate in the frontal lobes.

Animals↗

[Differentiation of efferent projections of the medial (cuneiform nucleus) and lateral areas of the reticular formation of the midbrain in the cat].

Efferent connections of medial (nucleus cuneiformis) and lateral regions of the caudal part of the midbrain reticular formation (mRF) were investigated by anterograde autoradiographic method in cat. Projections from the mRF ascend to the globus pallidus, substantia innominata, hypothalamus, subthalamus and nonspecific, associative and relay nuclei of the thalamus. Descending pathways terminate in the reticular formation of the brain stem. The conclusion is made that the cuneiform nucleus is rather a nonspecific than auditory centre. The lateral reticular region has strong projections to the lateral geniculate body and together with the parabigeminal nucleus forms the midbrain visual complex.

Animals↗

Short-term memory: the role of the midbrain reticular formation.

Low-intensity electrical stimulation of the midbrain reticular formation (MRF) in rats disrupted retention in a discrete-trail delayed alternation task independent of temporal locus of application of the stimulation. The stimulation did not appear to disrupt a motor set, have rewarding or aversive consequences, alter arousal level significantly, or affect encoding or retrieval processes. It is suggested that MRF stimulation might alter delayed alternation performance via neural and behavioral mechanisms associated with the maintenance of activated memory traces over short periods of time.

Animals↗

Cardiac input to medullary reticular formation: neuronal responses to CAO.

Responses of 46 medullary reticular neurons to coronary arterial occlusions (CAO) of the left anterior descending (LAD) and left circumflex (CX) coronary arteries were determined in chloralose-anesthetized cats paralyzed with pancuronium. Extracellular potentials were recorded from individual neurons, in the medial reticular formation, responsive to electrical stimulation of cardiopulmonary sympathetic afferents. CAO responses were characterized by one of three patterns. Cell activity changed during myocardial ischemia (IS response). Fifteen neurons were excited during ischemia (9 +/- 2.8 to 15 +/- 3.2 spikes/s for CX occlusion and 10 +/- 3.0 to 17 +/- 4.7 spikes/s for LAD occlusion), and two were inhibited (8 +/- 3.0 to 4 +/- 3.0 spikes/s). Cell activity changed at the onset or release of occlusion and rapidly adapted (ON response). Four cells were excited at the onset of LAD occlusion (2 +/- 1.4 to 10 +/- 6.0 spikes/s), 9 cells were excited at onset of CX occlusion (5 +/- 2.5 to 16 +/- 5.6 spikes/s), and 1 cell decreased its rate at onset of CX occlusion. A combination of ON and IS responses occurred in five cells (ON-IS response). Overall, 24 neurons exhibited at least one of these responses, and 22 cells were unaffected by CAO. Thirty neurons were tested for responses to CAO of CX and LAD; neurons most often exhibited different patterns of responses to CAO of each artery. Thirty-one of 34 cells tested exhibited qualitatively, but often not quantitatively, similar responses to cardiac ischemia and to application of bradykinin to epicardium of free wall of left ventricle. Results indicate that medullary neurons often respond differentially to occlusion of different coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Glycine-mediated inhibitory postsynaptic potentials in the medial pontine reticular formation of the rat in vitro.

Glycinergic neurotransmission was examined in rat medial pontine reticular formation neurons in vitro. Intracellular recordings using glass microelectrodes were made in acutely prepared brainstem slices 400 microns thick. Spontaneous and electrically evoked synaptic activity was blocked by the glycine antagonist strychnine (1-5 microM) but not by the GABA antagonists bicuculline methiodide (40 microM) or picrotoxin (40 microM). Strychnine-sensitive spontaneous and evoked postsynaptic potentials persisted in the presence of the glutamate antagonist (kynurenate, 1 mM). Whole-cell voltage-clamp recordings were carried out in organotypic cultures of rat brainstem. The reversal potential of synaptic currents and responses to exogenously applied glycine were similar and were sensitive to manipulations of the chloride equilibrium potential. Synaptic activity but not responses to exogenous glycine were blocked by tetrodotoxin (0.3 microM). These results indicate the presence of robust, chloride ion-mediated glycinergic inhibition of medial pontine reticular formation neurons, and suggest that glycinergic neurons play an important role in controlling pontine premotor circuitry.

Animals↗

The involvement of medullary reticular formation in the hypotensive effect of extracts from seeds of Cassia tora.

In pentobarbital anesthetized rats, the medial portion of the medullary reticular formation has been identified to be directly involved in the hypotensive effect of extracts from the seeds of Cassia tora. This conclusion was drawn from the observed decrease in arterial blood pressure following local injection of extracts of this herb into this reticular site and from its inability to promote hypotension when the same reticular site has been electrolytically lesioned. The role of the medullary reticular formation in the Cassia tora-induced hypotension was suggested to be one which modulates the basic cardiovascular reflexes, favoring a decrease in vasomotor tone.

Animals↗

[The role of stimulation of the medullary reticular formation on intracranial pressure in cold injured brain].

This study was carried out to study the effect of stimulation of the reticular formation of the medulla oblongata on intracranial pressure (ICP) and cerebral blood volume (CBV) in injured brain with increased ICP. CBV was measured by the photoelectric method from the parietal lobe. Seventeen hours prior to the experiments, cold induced edema was produced to increase basal ICP. In 15 cats, electric stimulation produced temporary increases in BP, ICP and CBV and progressive intracranial hypertension was never observed (Group A). In 9 animals, progressive increases in CBV and ICP up to 50 to 100 mmHg were evoked after cessation of stimulation (Group B). Prestimulation ICP in Group B was significantly higher than that of Group A. Rapid and simultaneous increases in ICP and CBV following stimulation strongly suggested that global increments of CBV secondary to loss of cerebral vasomotor tonus were responsible for producing progressive intracranial hypertension. In Group B, the stimulation electrodes were invariably located at the area of the nucleus reticularis parvocellularis and gigantocellularis. Our experimental results show that in increased ICP a stimulated or irritable condition of the medullary reticular formation will cause acute progressive intracranial hypertension.

Animals↗

Substantia nigra projection to medullary reticular formation: relevance to oculomotor and related motor functions in the cat.

Wheat germ lectin-horseradish peroxidase was injected into the medial medullary reticular formation in 4 cats. Retrogradely labeled cell bodies were observed in the ipsilateral substantia nigra pars reticulata and bilaterally in the superior colliculus, oculomotor nucleus and fastigial nucleus of the cerebellum. The nigral projection to this reticular formation area, which receives diffuse afferents from cortex, cerebellum, oculomotor system and vestibular nucleus and projects to spinal cord, may be of some relevance in understanding the nigral role in postural, head- and eye-movement control.

Animals↗

Golgi-like immunoperoxidase staining of dopamine neurons in the reticular formation of the rat brainstem using antibody to tyrosine-hydroxylase.

The distribution and morphology of presumed dopaminergic neurons within the reticular formation (RF) and the ventrolateral tegmental area (VLT) were studied by using a specific antibody to the enzyme that converts tyrosine to dihydroxyphenylalanine, tyrosine-hydroxylase (TH), in combination with a sensitive immunoperoxidase method (Hsu et al., '81). Incubation of thick (70-120 micron) sections for 3-5 days in high dilutions of antibody resulted in staining of TH-immunoreactive neurons in a Golgi-like fashion. Analysis of serial sections cut in the coronal, horizontal, and parasagittal planes revealed an extensive system of TH-positive neurons in the RF and VLT extending from the Edinger-Westphal nucleus caudally to the level of the decussations of the superior cerebellar peduncle. Within this region, the TH-positive cells belong to two subgroups: (1) a relatively well-defined population of cells aggregated in the reticular formation (corresponding to cell group A8 of Dahlström and Fuxe, '64), and (2) a more loosely defined group of cells that appears to be continuous with the cells of the nucleus raphe linearis. This latter cell group extends laterally from the midline to the nucleus parapeduncularis. An analysis of the individual TH-immunoreactive cells revealed large differences in their morphology. Thus, the somata of TH-positive cells in the RF and the VLT are fusiform, ovoid, or triangular. A majority of the TH neurons are of medium (long axis: 15-35 micron) to large (long axis: 35-40 micron size. While the cells in the A8 area appeared relatively homogeneous, the TH-positive cells of the VLT showed great variations in dendritic branching pattern and orientation. Taken together, the present study has shown that within the RF and the VLT, the TH-immunoreactive neurons are more numerous than hitherto recognized, and that this cell group consists of a morphologically heterogeneous population of dopamine-synthesizing neurons.

Animals↗

Locomotion produced in mesencephalic cats by injections of putative transmitter substances and antagonists into the medial reticular formation and the pontomedullary locomotor strip.

The purpose of this study was to determine the distribution of cells in the medial reticular formation (MRF) and the pontomedullary locomotor strip (PLS), which can induce locomotion when activated. Controlled microinjections of neuroactive substances (Goodchild et al., 1982) into the MRF or PLS were made in order to activate cell bodies in those areas. The ability of trigeminal receptive field stimulation to induce locomotion before and after drug infusion into the PLS was also assessed since the PLS and the spinal nucleus of the trigeminal nerve are similar in their anatomical distribution. Experiments were performed on precollicular-postmamillary decerebrate cats walking on a treadmill. Injections of glutamic acid (GA; 500 nmol) into the MRF produced locomotion that was antagonized by infusion of glutamic acid diethyl ester into the same spot. Decreases in the current threshold for locomotion produced by electrical stimulation of the MRF were observed when the MRF was infused with either GA (40-80 nmol), DL-homocysteic acid (DL-HCA; 200 nmol), or picrotoxin (PIC; 15 nmol). Injections of GA (100 nmol), DL-HCA (700 nmol), PIC (10-50 nmol), and substance P (2 nmol) into the PLS also produced locomotion. Locomotion produced by injections of PIC into the PLS was blocked by infusion of equal amounts of muscimol or GABA. Effective PLS injection sites were all confined to the trigeminal spinal nucleus or immediately ventral and medial to this in the adjacent lateral reticular formation. Trigeminal nerve peripheral field stimulation evoked locomotion after microinjection of PIC into the PLS, although this same facial stimulus was not effective prior to drug injection. We conclude that the MRF and PLS regions of the cat brain stem contain cells that produce locomotion when chemically stimulated, and we suggest that the PLS is closely related to or synonymous with the spinal nucleus of the trigeminal nerve. Furthermore, we suggest that stimulation of trigeminal afferents is analogous to stimulation of segmental afferent pathways in the production of locomotion (Sherrington, 1910; Jankowska et al., 1967; Afelt, 1970; Budakova, 1972; Grillner and Zangger, 1979).

Animals↗

Catalepsy induced by carbachol microinjected into the pontine reticular formation of rats.

Rats were implanted stereotaxically with permanent guide tubes aimed at the pontine reticular formation. Carbachol was microinjected in the awake, freely moving rats. Catalepsy was evaluated with the horizontal bar test. Intense and long-lasting, dose-dependent catalepsy was observed following microinjections of 2-8 micrograms of carbachol. Pretreatment with intraperitoneally administered scopolamine significantly reduced the cataleptogenic effect of carbachol. These results show that the pontine reticular formation is part of the neuroanatomical substrate of catalepsy induced by cholinergic drugs.

Animals↗

Projections from the red nucleus to the parvicellular reticular formation and the cervical spinal cord in the rat, with special reference to innervation by branching axons.

After biotinylated dextranamine injection into the dorsal part of the red nucleus (RN) in the rat, labeled axons were distributed contralaterally in the lateral tegmental field including the parvicellular reticular formation (RFp), and ipsilaterally in the medial reticular formation. In the cervical spinal cord, labeled axons were present bilaterally with a contralateral dominance mainly in laminae V-VI and the dorsal part of laminae VII. After ipsilateral injections of rhodamine dextranamine, Fluoro-ruby (FR) into the RFp and Fluoro-gold (FG) into the upper cervical spinal cord, a population of FR-labeled neurons was found in the dorsal part of the contralateral RN, whereas the majority of FG-labeled neurons were located more ventrally. However, some of them were intermingled with FR-labeled neurons, and as many as one-third of FR-labeled neurons were labeled with FG. After combined injections of FR into the RFp and FG into the lower cervical spinal cord, RN neurons labeled with FG existed more ventrally than those retrogradely labeled from the upper cervical spinal cord, and less than 10% of FR-labeled neurons were labeled with FG. The present data suggest that axon collateral innervation of the RFp and the upper cervical spinal cord by single RN neurons may be responsible for coordinating head and orofacial movements.

Animals↗

Effects of stimulating in raphe nuclei and in reticular formation on response of spinothalamic neurons to mechanical stimuli.

1. The purpose of these experiments was to compare effects of electrical stimuli applied in two regions of the brain stem that are the sites of origin of descending bulbospinal systems; namely, the nucleus gigantocellularis of Brodal (7) and the nucleus raphe magnus, on the responses of lumbosacral spinothalamic neurons to mechanical stimuli. 2. In cats anesthetized with alpha-chloralose, stimulating in either of these structures with single pulses of current while the spinothalamic neuron was tonically activated by a sustained mechanical pressure resulted in an increase in the excitability of the cell followed by a prolonged suppression of its impulse activity. 3. For different neurons, the latency of the excitation ranged from 4 to 18 ms following the brain stem stimulus, while the latency of the suppression ranged from 16 to 34 ms. 4. In general, the effects of stimulating in the reticular formation and in the raphe nuclei were similar. although quantitative differences were found in the effects of each on different spinothalamic neurons. On the basis of these two studies, it is argued that the reticulospinal and raphe-spinal systems exert qualitatively similar effects on the responses of spinothalamic neurons evaluated in this experiment. 5. A comparison of the magnitudes of the suppression phase evoked from several different sites in the ipsilateral reticular formation and nucleus raphe magnus suggests that the descending systems arising from both these structures may be quite heterogeneous. 6. Stimulation of both regions of the brain stem produced a much greater suppression of the response of the spinothalamic neurons to slowly changing or sustained mechanical stimuli than to transient stimuli. It is suggested that the effects of descending systems arising both in the raphe nuclei and in the reticular formation on the responses of spinothalamic neurons to a mechanical stimulus are at least as dependent on the time course of the mechanical stimulus as they are on its intensity.

Animals↗