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Arrangement of neurons in the medullary reticular formation and raphe nuclei projecting to thoracic, lumbar and sacral segments of the spinal cord in the cat.

The distribution of neurons in the medullary reticular formation and raphe nuclei projecting to thoracic, lumbar and sacral spinal segments was studied, using the technique of retrograde transport of horseradish peroxidase (HRP), alone or in combination with nuclear yellow (NY). Retrogradely labeled cells were observed in the lateral tegmental field (FTL), paramedian reticular nucleus, magnocellular reticular nucleus (Mc), in the gigantocellular nucleus (Gc), lateral reticular nucleus (LR), lateral paragigantocellular nucleus (PGL), rostral ventrolateral medullary reticular formation (RVR), as well as in the medullary raphe nuclei following the injection of the tracer substance(s) into various levels of the spinal cord. The FTL, the ventral portion of the paramedian reticular nucleus (PRv), Mc, LR, PGL and the raphe nuclei were found to project to thoracic, lumbar and sacral spinal segments. This projection was bilateral; the contralaterally projecting fibers crossed the midline at or near their termination site. The dorsal portion of the paramedian reticular nucleus (PRd), Gc and the RVR projected mainly to thoracic segments. This projection was unilateral. Experiments in which the HRP-injection was combined with lesion of the spinal cord showed that some descending raphe-spinal axons coursed presumably alongside the central canal. Experiments with two tracer substances suggested that some reticulo- and raphe-spinal neurons had axon collaterals terminating both in thoracic and sacral spinal segments.

Animals↗

Response properties and functional organization of neurons in midline region of medullary reticular formation of cats.

Extracellular single-unit recordings were made in the anesthetized cat from neurons within the medullary raphe nuclei and nearby reticular formation. The descending axons from some of these neurons were characterized in terms of length, conduction velocity, and location within the white matter of the spinal cord. The sensory properties were characterized following somatic, baroreceptor, visual, and auditory stimuli. The mean conduction velocities of the descending axons from neurons in the medullary raphe nuclei and in the magnocellular tegmental field (26 m/s) were significantly slower than the mean conduction velocities of units in the regions immediately dorsal to them (50 m/s). Action potentials in neurons in the medullary raphe nuclei and in the magnocellular tegmental field were evoked by anti-dromic stimulation from the dorsolateral portion of the spinal cord (30 of 43, 70%), whereas neurons located in more dorsal regions along the midline and in the reticular formation projected into the ventral columns (18 of 25, 72%). Neurons were most easily activated by a tap stimulus to the body surface. This stimulus activated 84% of the neurons tested. The receptive fields were large, often including the four limbs, back, and head. Tap-sensitive neurons were found throughout the regions investigated. Stimulation of hair receptors activated 37% of neurons tested, whereas 19% responded to a high-intensity cutaneous stimulus (pinch), 35% responded to baroreceptor stimuli, 32% responded to visual stimuli, and 33% responded to auditory stimuli. Neurons responsive to pinch were likely to respond to baroreceptor stimuli and unlikely to respond to visual stimuli. Neurons responsive to visual stimuli were likely to respond to auditory stimuli.

Afferent Pathways↗

Importance of cholinergic, GABAergic, serotonergic and other neurons in the medial medullary reticular formation for sleep-wake states studied by cytotoxic lesions in the cat.

Previous evidence has suggested that neurons in the medial medullary reticular formation play a critical role in the modulation of forebrain and spinal cord activity that occurs during the sleep-waking cycle and particularly in association with the state of paradoxical sleep. The importance of these neurons, including cholinergic, serotonergic and GABAergic cells [Holmes C. J. et al. (1994) Neuroscience 62, 1155-1178] for sleep-wake states was investigated after their destruction with the neurotoxin quisqualic acid injected into the medullary gigantocellular and magnocellular tegmental fields in cats. To assess the effects of the neuronal loss, polygraphic recording and behavioural observations were performed in baseline and for three weeks after the lesion, and the changes in these measures were correlated with the volume of destruction of medullary regions and the numbers of chemically identified cells within those regions. Following the cytotoxic lesions, which affected approximately 60% of the medullary gigantocellular and magnocellular tegmental fields, there was a significant reduction in the amount of paradoxical sleep (to a mean of 64% of baseline) during the first postlesion week, that recovered variably across cats in the second and third weeks. There was little to no change in the amount or organization of waking and slow wave sleep. The individually variable amounts of postlesion paradoxical sleep were correlated positively with the number of surviving cholinergic cells, negatively with the number of surviving serotonergic cells and positively with the ratio of surviving cholinergic or GABAergic cells to serotonergic cells. The most marked effect of the lesion was a substantial increase in the amplitude of the nuchal electromyogram during slow wave sleep (to 198%) and paradoxical sleep (to 378% of baseline in the first postlesion week). The increase in muscle tone was associated with movements of the head, neck or limbs during paradoxical sleep. Although, in some cats, the abnormal neck muscle tone decreased with time, limb movements continued to occur during paradoxical sleep for the duration of the experiment. The ratio of the total number of remaining cholinergic or GABAergic cells to serotonergic cells correlated negatively with the increased muscle tone and/or movements. It was concluded that the neurons of the medial medullary reticular formation contribute to, but are not necessary for, the generation of paradoxical sleep, and have particular importance for the regulation of muscle tone and inhibition of movement during this state.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Collateralization of cerebellar efferent projections to the paraoculomotor region, superior colliculus, and medial pontine reticular formation in the rat: a fluorescent double-labeling study.

Collateralization of cerebellar efferent projections to the oculomotor region, superior colliculus (SC), and medial pontine reticular formation (mPRF) was studied in rats using fluorescent tracer substances. In one group, True Blue (TB) was injected into the oculomotor complex (OMC), including certain paraoculomotor nuclei and supraoculomotor ventral periaqueductal gray (PAG), and Diamidino Yellow (DY) was injected into the medial pontine reticular formation (mPRF) or pontine raphe. The largest number of single-TB-labeled (paraoculomotor-projecting) cells was observed in the medial cerebellar nucleus (MCN) and posterior interposed nucleus (PIN), whereas the largest number of single-DY-labeled (mPRF-projecting) cells was in the MCN. Double-TB/DY-labeled cells were present in the caudal two-thirds of the MCN, suggesting that some MCN neurons send divergent axon collaterals to the paraoculomotor region and mPRF. In another group, TB was injected into the SC and DY into the mPRF. The largest number of single-TB-labeled (SC-projecting) cells was in the PIN, although a considerable number of cells was observed in the caudal MCN, and ventral lateral cerebellar nucleus (LCN). Single-DY-labeled (mPRF-projecting) neurons were primarily located in the central and ventral MCN, but were also present in the lateral anterior interposed (AIN) and in the LCN. Double-TB/DY-labeled neurons were observed in the caudal two-thirds of the MCN and in the central portion of the LCN. The most significant new findings of the study concerned the MCN, which not only contained neurons that projected independently to the paraoculomotor region, SC, and mPRF, but also contained a considerable number of cells which collateralized to project to more than one of these nuclei. The possibility that the MCN projects to the supraoculomotor ventral PAG (containing an oculomotor interneuron system) and to the mPRF, which in the cat and monkey contain neural elements essential to the production of saccadic eye movements, is discussed. The anatomical findings suggest that the MCN in the rat plays an important role in eye movement.

Animals↗

The behaviour of acetylcholinesterase activity in neurons of the bulbous part of the reticular formation in albino rats after bilateral vagotomy.

The influence of a bilateral vagotomy on the acetylcholinesterase activity (AChE) in the neurons of the bulbous part of the reticular formation of albino rats was investigated. An increase in the reaction to acetylcholinesterase (AChE) was ascertained in the large as well as the small neurons 8 h after the transection of the vagus nerves, which indicates their decreased activity. It may be assumed that a bilateral vagotomy causes a decrease in the activity of cholinergic mechanisms within the periphery of the reticular formation neurons.

Acetylcholinesterase↗

Ipsiversive turning behaviour after discrete unilateral lesions of the dorsal mesencephalic reticular formation by kainic acid.

Discrete axon-sparing lesions were placed unilaterally in the mesencephalon by the local injection of kainic acid. Unilateral lesions of the dorsal reticular formation just beneath the superior colliculus and lateral to the periacqueductal grey resulted in consistent ipsiversive apomorphine-induced circling. Only weak motor asymmetries were observed after unilateral lesions restricted to the superior colliculus or to the periacqueductal grey. The results indicate that the dorsal mesencephalic reticular formation plays an essential role as an output station for striatal postural functions.

Animals↗

The brain stem reticular formation in schizophrenia.

Post-mortem brain tissue was obtained from four patients with schizophrenia and five controls to study cell groups in the brain stem reticular formation. Cholinergic neurons in the pedunculopontine nucleus (PPN) and lateral dorsal tegmental nucleus (LDT) were labeled using nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase histochemistry, while catecholaminergic neurons of the locus ceruleus (LC) were labeled immunocytochemically using an antibody to tyrosine hydroxylase. In schizophrenic patients, there were increased numbers of neurons in the PPN labeled by NADPH-diaphorase and reduced cell size in the LC. These results implicate the reticular formation as a possible pathophysiological site for at least some patients with schizophrenia. This also suggests that some of the deficits observed may be based on faulty neurodevelopment.

Aged↗

The opiate antagonist naloxone does not consistently block inhibition of spinal nociceptive transmission produced by stimulation in lateral midbrain reticular formation of the cat.

Electrical stimulation in the lateral midbrain reticular formation (LRF) inhibited the responses of spinal dorsal horn neurons to noxious (50 degrees C) skin heating. Systemic administration of naloxone (0.1-2 mg/kg) had no effect on inhibition produced by LRF stimulation in 10 units, while this inhibition was partially blocked in 3 units. The results indicate that endogenous opiates are not primarily involved in mediating descending inhibition from LRF stimulation.

Afferent Pathways↗

Reticular formation neurons related to tongue movement in the behaving cat.

We have found a number of cells related to tongue movement in the medial brain stem reticular formation of the unanesthetized cat. These cells constituted less than 2% of the cells tested in this region and were distributed throughout several nuclei in the medulla and pons including nucleus reticularis pontis caudalis, nucleus reticularis gigantocellularis, and the border between nucleus reticularis paramedianus and nucleus interfascicularis hypoglossi. All observed tongue movement cells (N = 6) fired maximally during protrusive tongue movements. One medullary cell discharged primarily during the protrusive tongue movement to the ipsilateral side, whereas no lateral preference was detected in the other cells. Gustatory and mechanosensory stimulation of the tongue was unnecessary for inducing discharge in these cells. Tongue movement-related cells shared several characteristics that differentiated them from adjacent reticular formation cells, including absence of response to startle-inducing auditory stimuli and low levels of spontaneous waking and sleep activity. In two pontine cells located near the trigeminal motor nucleus, spike-triggered averages of tongue EMG revealed a short-latency (5 ms) inhibitory effect on the ipsilateral genioglossus muscle by the units' discharge. We suggest that neurons of this type might be involved in tongue-jaw coordination during mastication, licking, and grooming.

Action Potentials↗

Cardiac input to medullary reticular formation: neuronal responses to mechanical stimuli.

Neurons in the medullary reticular formation were tested for responses to mechanical stimuli applied to the heart in cats anesthetized with chloralose and paralyzed with pancuronium. In most experiments baroreceptors were denervated. Aortic occlusion excited 15 neurons (19%) and decreased the mean discharge rates of five neurons (6%). Discrete probing of the heart elicited one to three spikes from 18 of 27 neurons tested. Thirteen of these cells had defined cardiac receptive fields; fields were large, often encompassing most of the left ventricle. Of 12 neurons tested for responses during fibrillation, 8 were excited, 2 were inhibited, and 2 were unaffected. Neurons often exhibited different sensitivities to these mechanical stimuli, as well as to ischemia produced during coronary arterial occlusion. Neurons were more likely to respond to stimuli that affected a large mass of myocardium. In addition to cardiac input, 98% of neurons in this study also received input from at least one additional sensory modality, and 39 cells were excited by somatic, auditory, and visual stimuli. Results indicate that medullary reticular neurons are responsive to mechanical events in the heart as well as to myocardial ischemia and respond to other sensory modalities.

Afferent Pathways↗

Facilitation of generalization performances in spatial learning problems by posttrial stimulation of the mesencephalic reticular formation.

The effects of low posttrial stimulation of the mesenphalic reticular formation (MRF) on spatial learning problems were studied in two consecutive stages. First, the performances of stimulated (S) and no-stimulated (NS) subjects were assessed in a reconvergent three-arm maze. Secondly, the same animals were tested in a generalization paradigm, since they had to solve a similar task in a radial four-arm maze, each group being divided into newly stimulated (S-S, NS-S) or no-stimulated (S-NS, NS-NS) subjects. In the first experiment, no differences were found between the acquisition processes of groups S and NS. Conversely, in the second experiment, previously stimulated animals (S-S and S-NS) showed better generalization of the experimental rule. The results are discussed in terms of preservation of the neural activity after the early MRF stimulation. From a functional point of view, our data indicate that an enhancement of the neural activity during acquisition facilitates not only a high accessibility of memories concerning the experimental rule in a subsequent similar situation but also the capability to apply a previously elaborated response system in a more complex situation.

Animals↗

Crossed forelimb extension produced in thalamic cats by injection of putative transmitter substances into the paralemniscal pontine reticular formation.

To analyze the descending pathways of the paralemniscal pontine reticular formation (PLRF), a technique was used for the selective activation of cell bodies by localized injection of putative neurotransmitters in the PLRF. When a small amount (less than 0.1 microliter) of 0.1 M glutamate was injected into the PLRF unilaterally in thalamic cats, the forelimb contralateral (c-forelimb) to the injection was extended, and occasionally the ipsilateral forelimb was flexed. These responses were similar to those obtained by electrical stimulation of the PLRF, but were relatively weaker. Unit spikes of PLRF neurons were increased in frequency following administration of glutamate. The latent periods and durations of increases in spike frequency varied depending on the concentration and quantity of the glutamate solution, and were roughly similar to those of the extensor EMG in the c-forelimb. Since the firing of PLRF neurons preceded the EMG with 11 ms latency, the unit spike of PLRF neurons could be used as a triggering signal to observe a spike triggered averaged EMG response in the extensor muscle of the c-forelimb. Results similar to those with glutamate were observed upon administration of quisqualate, kainate and aspartate. The most effective compound was quisqualate. Application to the PLRF of 1-naphthylacetyl spermine (1-NA-Spm), an analogue of the natural spider toxin JSTX-3 and an antagonist of glutamate, suppressed both the PLRF neuron activity and the extensor EMG of the c-forelimb. These observations suggest that extensor muscles of the forelimb are excited by the contralateral PLRF, perhaps via the crossed reticulospinal tract from the PLRF. PLRF neurons may be activated by glutamate (quisqualate) receptors.

Animals↗

The interstitial nucleus of Cajal in the midbrain reticular formation and vertical eye movement.

Bilateral lesions of the midbrain reticular formation within, and in the close vicinity of, the interstitial nucleus of Cajal (INC) result in the severe impairment of the ability to hold eccentric vertical eye position after saccades, phase advance and decreased gain of the vestibulo-ocular reflex (VOR) induced by sinusoidal vertical rotation. In addition, the INC region of alert animals contains many burst-tonic and tonic neurons whose activity is closely correlated with vertical eye movement, not only during spontaneous saccades, but also during the VOR, smooth pursuit and optokinetic eye movements. Although their activity is closely related to these conjugate vertical eye movements, it is different from the oculomotor motor neuron activity. These results indicate that the INC region is involved in, and indispensable for, some aspects of eye position generation during vertical eye movement. Further comparison of INC neuron discharge with eye movements during two special conditions indicates that the INC region alone cannot produce eye position signals. First INC neuron discharge shows no response or an 80 degrees phase advance (close to the expected value if there is no integration) in the dark compared to the light during sinusoidal vertical linear acceleration in alert cats. Second, during rapid-eye-movement (REM) sleep, the discharge of INC neurons is no longer correlated with eye position. These results imply that the INC is not the entire velocity-to-position integrator, but that it has to work with other region(s) to perform the integration. A close functional linkage has been described between vertical-eye-movement-related neurons in the INC region and vestibulo-ocular relay neurons related to the vertical semicircular canals in the vestibular nuclei. It has been suggested that both are the major constituents of the common neural integrator circuits for vertical eye movements.

Animals↗

[Characteristics of the effects of the midbrain reticular formation on the heart and respiration in exposure to centripetal accelerations].

Experiments were carried out on white rats and rabbits exposed to transverse accelerations of 6--10 g for 5 min. Before, during and after centrifugation the reticular formation of the midbrain underwent high-frequency electric stimulation. During centrifugation the inhibitory effects of the reticular formation on the cardiorespiratory rhythm decreased, whereas stimulatory effects either remained unchanged or increased.

Acceleration↗

Electrophysiology of the dorsolateral mesopontine reticular formation during Pavlovian conditioning in the rabbit.

Extracellular single-unit recording methods were used to study the activity of neurons within a restricted portion of the dorsolateral mesopontine reticular formation, an area which includes the parabrachial, pedunculopontine tegmental and cuneiform nuclei. Recordings were obtained during presentations of unfamiliar and familiar sensory stimuli, during Pavlovian differential conditioning procedures that elicited conditioned bradycardia, and while stimulating the amygdaloid central nucleus to identify neurons that projected to, or received projections from, the amygdaloid central nucleus. Activity in most dorsolateral mesopontine reticular neurons was altered during sensory stimulation, and the convergence of auditory and somatic inputs onto single neurons was common. Moreover, neural responses were often of a different magnitude and/or direction to auditory stimuli that were unfamiliar vs familiar vs reinforced (paired with pinna stimulation), and many of these differentially responsive neurons were activated orthodromically by stimulation of the amygdaloid central nucleus. In contrast, neurons activated antidromically by stimulation of the amygdaloid central nucleus were relatively quiescent during all phases of the experiment. Results are discussed in relation to current hypotheses concerning the functional significance of various neuronal subpopulations within the dorsolateral mesopontine reticular formation during Pavlovian conditioning.

Amygdala↗

Amygdaloid pathway to the trigeminal motor nucleus via the pontine reticular formation in the rat.

The connections of the amygdala with the trigeminal motor nucleus were studied by light and electron microscopy. Horseradish peroxidase (HRP) experiments showed that the pontine reticular formation, ventromedial to the spinal trigeminal nucleus at the level rostral to the genu of the facial nerve, receives fibers from the central nucleus of the amygdala ipsilaterally and sends fibers to the trigeminal motor nucleus contralaterally. Electron microscopic observations were carried out on the pontine reticular formation after electrolytic lesions in the central nucleus of the amygdala and HRP injections into the contralateral trigeminal motor nucleus were made on the same animal. These experiments using the combined degeneration and HRP technique clearly demonstrated that degenerating amygdaloid fibers made synaptic contacts with retrogradely labeled neurons.

Amygdala↗

Frontal eye field projection to the paramedian pontine reticular formation traced with wheat germ agglutinin in the monkey.

Injections of the retrograde tracer [125I]wheat germ agglutinin have been placed in different areas of the paramedian pontine reticular formation (PPRF), a well known premotor center for gaze control. Experiments in 5 monkeys revealed 3 major sources of input: (1) bilateral projections from the so-called frontal eye field (FEF), which is situated in the frontal cortex around the arcuate sulcus; (2) the intermediate and deep layers of mainly the contralateral superior colliculus; and (3) ipsilateral projections from brainstem structures such as the accessory oculomotor nuclei (nucleus interstitialis of Cajal, nucleus of Darkschewitsch, and nucleus of the posterior commissure), the mesencephalic reticular formation, the vestibular nuclei, the nucleus prepositus hypoglossi, and the cerebellar fastigial nucleus. The results are compared with previous anatomical investigations and confirm the electrophysiologically demonstrated FEF-PPRF-abducens disynaptic pathway.

Animals↗

Effects of bemegride on the sensory responses of neurons in the hippocampus and brain stem reticular formation.

Administration of subconvulsant doses of bemegride results in extensive enhancement of sensory responsiveness to auditory, visual, somatosensory and vibrissa stimulation of neurons in the medullary and mesencephalic reticular formation (RF). This effect is not altered by cord transection. Most neurons in the dorsal hippocampus do not show enhanced sensory responsiveness. In the minority of hippocampal neurons which do show enhancement the effect is much less extensive than that seen in the RF despite larger doses of bemegride. The enhancement of RF neuronal response may involve the reversal of repetition induced response attenuation ('habituation') and reductions in response threshold. During EEG seizures the firing of neurons in RF and hippocampus are temporally correlated with the spikes in the cortical EEG. The effects of bemegride on RF neurons are similar to those previously reported for strychnine and pentylenetetrazol and preliminary studies with physostigmine and bicuculline. These findings further extend the concept that a relatively selective enhancement of the sensory responses of brain stem reticular formation neurons may be indicative of a general neuronal effect of convulsants which may play an important role in the initiation of sensory-induced seizures.

Animals↗