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Spatial interactions and stimulus-response relations of unit responses evoked by somato-sensory stimuli in the feline caudal medullary reticular formation.

Responses of neurons in the bulbar reticular area to separate and simultaneous stimulation of the forelimbs were recorded extracellularly in chloralose-anaesthetized cats. On increasing the stimulus intensity the number of spikes per response increased while the initial latency and interspike intervals decreased in accordance with the functional property of the neuron. Responses evoked by simultaneous stimulation displayed more spikes and a shorter latency than those evoked by separate stimuli of corresponding intensities. The differences in the responses evoked simultaneously and the sums of responses evoked separately showed characteristic distributions as a function of the latter. Three types of distribution were distinguished. The results indicate that stimulus-response relations play a determining role in the mechanism of spatial integration.

Action Potentials↗

Correlation of prostaglandin release from the cerebral cortex of cats with the electrocorticogram, following stimulation of the reticular formation.

1. Prostaglandin-like material has been found in superfusates of cerebral cortex in unanaesthetized encéphale isolé cat preparations.2. The material was assayed on the isolated rat uterus and identified by thin-layer chromatography.3. The level of spontaneous release of prostaglandin-like material was greater than that which had been found in anaesthetized preparations and it increased further with electrical stimulation of the reticular formation which induced electrocortical arousal.4. Chlorpromazine (1.0-8.0 mg/kg) not only depressed the spontaneous release but blocked the increase evoked by stimulation concomitantly with blocking electrocortical arousal. Increasing the stimulating voltage to restore the arousal response also restored the evoked release of prostaglandins.5. Most of the prostaglandin-like material released spontaneously was represented by E type compounds, but the increase with stimulation was mainly of F compounds.

Animals↗

Effect of lithium on circadian activity of AChE (EC 3.1.1.7) in the reticular formation of mouse brain stem under LD 12:12.

The investigation was carried out on male mice 6-8 weeks old. Control animals were fed standard chow without lithium, while the experimental ones received on additional 10 mmol LiCl/kg of chow. After 30 days feeding, 7 mice at a time were killed every 4h. The activity of free AChE was assessed in the brain stem reticular formation according to the method of Ellman. The results were statistically analyzed using Student's t-test and Fisher test. Parameters of periodic function were then applied to the means obtained by the method of least-squares. In both the control and experimental groups diel changes in the AChE activity were observed. Acrophase activity occurred in the control group at 1956. In the experimental group lithium caused a shift in acrophase to 0551. It may therefore be supposed that lithium not only affects the duration of the rhythm period but also shifts its phase by 1800. This could be relevant to the therapeutic use of lithium in manic-depressive patients who may present advancing phase of circadian rhythms.

Acetylcholinesterase↗

Abnormal cortical unit activity of the reticular formation.

Many neurological disorders are accompanied by abnormal nerve activity. However, the exact causes of this abnormal nervous activity has never been determined. Based upon my research, I propose a theory that the underlying cause of many types of neurological disorders such as minor epilepsy and narcolepsy is an abnormally functioning Na+/K+ ATPase pump at the molecular framework of the brain, notably the brainstem reticular formation (locus coerulus) and cerebellum in this particular case. The excessive and repetitive nerve activity within localized areas of the brain caused by abnormally functioning molecular Na+/K+ ATPase ion pumps may be the primary and true causes of many different types of neurological disorders since constant depolarizations of the cell membrane causes abnormally excessive amounts of certain neurotransmitters to be released. The type of neurological disorder may be a function of the abnormally occurring Na+/K+ ATPase molecular ion pump's localization within the neurological framework of the brain. To focus on my theory of repetitive nervous activity from abnormal inhibitive or defective Na+/K+ ATPase pumps, I have chosen to analyze minor epilepsy and narcolepsy intentionally. What is found is that the abnormal release of neurotransmitters during epileptic seizures or narcoleptic sleep episodes is secondary to the abnormal neuronal systematic framework underlying Na+/K+ membrane potentials since an abnormally inhibited or defective Na+/K+ ATPase pump has a direct electrogenic effect on the membrane potential.

Cerebellum↗

Neurons of the superior olivary complex do not excite startle-mediating neurons in the caudal pontine reticular formation.

The acoustic startle response is an important mammalian model for studying the cellular mechanisms of emotions and learning. Lesions in the superior olivary complex have been shown to attenuate the amplitude of the acoustic startle response, thus a substantial contribution of these neurons to the startle response was proposed. We here explored the putative connection of olivary neurons to the startle-mediating giant neurons in the reticular formation in rat brain slices in vitro. Tracing studies and electrical stimulation in the superior olivary complex revealed a strong connection; however it was not possible to distinguish between olivary neurons and traversing auditory fibres. Glutamate uncaging in the olivary complex excited a subpopulation of olivary neurons but never PnC giant neurons, as shown by patch-clamp recordings. This clearly contradicts an excitatory connection from olivary neurons to PnC giant neurons and thus an involvement of the superior olivary complex in eliciting a startle response.

Animals↗

Inhibition of the responses of neurons in the rat spinal cord to noxious skin heating by stimulation in midbrain periaqueductal gray or lateral reticular formation.

Single units responsive to noxious heating of glabrous hindfoot skin were recorded in the lumbar spinal cord of rats anesthetized with sodium pentobarbital. Unit responses to heat stimuli (e.g. 50 degrees C, 10 s) delivered at 2-min intervals were stable and were markedly suppressed during stimulation (100-ms pulse trains at 100 Hz, 3/s, 25-400 microA) in the midbrain periaqueductal gray (PAG) or lateral reticular formation (LRF). Inhibition did not appear to outlast the midbrain stimulation period. By systematically varying the position of an array of 3 or 5 stimulating electrodes, we observed that stimulation in PAG and subjacent tegmental areas, as well as in widespread regions of the LRF bilaterally, suppressed unit responses to noxious skin heating. The degree of suppression of unit responses increased with graded increases in PAG or LRF stimulation intensity. LRF appeared to be more efficacious than PAG stimulation, based on lower currents at threshold, as well as on significantly greater slopes in current-inhibition plots for LRF compared to PAG stimulation. Unit responses increased linearly with graded increases in stimulus temperature from 42 to 54 degrees C. Slopes of temperature-response lines were reduced during PAG stimulation with no change in response threshold, while temperature-response lines were shifted in a parallel manner toward higher temperatures during LRF stimulation with an increase in response threshold. The results suggest that differential inhibitory systems are activated by PAG or LRF stimulation and are discussed in relation to previous findings in the cat and as a possible mechanism of stimulation-produced analgesia.

Animals↗

Influence of rubrospinal tract and the adjacent mesencephalic reticular formation on the activity of medullary respiratory neurons and the phrenic nerve discharge in the rabbit.

Suprapontine brain sites acting on the central respiratory system have been demonstrated to give rise to inspiratory as well as expiratory facilitatory effects. In the present study the inspiratory inhibitory effect which has been reported in the cat to be elicited consistently by electrical stimulation of the rubrospinal tract and the adjacent mesencephalic reticular formation was examined in the urethane-anaesthetized rabbit. Stimulation of these sites with single electrical shocks of moderate intensity induced a short latency (onset after 3.0 ms) transient (duration: 29 ms) inhibition of the phrenic nerve activity (PHR). Short volleys of stimuli applied in mid- to late-inspiration led to a premature off-switch of inspiration. The extracellularly recorded discharge activity of the different types of medullary respiration-related units (RRU) reflected these alterations, accordingly. Axonal connections of RRU with mesencephalic structures were evaluated. Examination of orthodromic responses of medullary RRU to stimulation of this pathway revealed that most bulbospinal inspiratory neurons (10 out of 13) were paucisynaptically inhibited after short latency (at least 1.2 ms). The conduction time from bulbospinal inspiratory neurons to the recording site of PHR was 1.6 ms. Thus, a disynaptic pathway--including bulbospinal inspiratory neurons--is suggested inducing inspiratory inhibition 3.0 ms after single shock midbrain stimulation. This inhibition results in disfacilitation of phrenic motoneurons. The fact that extensive electrolytic lesions of the pneumotaxic center in rostral pons did not abolish the observed inspiratory inhibitions excludes these structures from being involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhibition of the responses of cat dorsal horn neurons to noxious skin heating by stimulation in medial or lateral medullary reticular formation.

Responses of single lumbar dorsal horn units to noxious radiant heating (50 degrees C, 10 s) of glabrous footpad skin were recorded in cats anesthetized with sodium pentobarbital and 70% nitrous oxide. The heat-evoked responses of 37/40 units were reduced during electrical stimulation (100 ms trains, 100 Hz, 3/s, 25-600 microA) in the medullary nucleus raphe magnus (NRM) and/or in laterally adjacent regions of the medullary reticular formation (MRF). Inhibition was elicited by stimulation in widespread areas of the medulla, but with greatest efficacy at ventrolateral sites. The magnitude of inhibition increased with graded increases in medullary stimulation intensity. Mean current intensities at threshold for inhibition or to produce 50% inhibition were higher for NRM than for MRF sites. Units' responses to graded noxious heat stimuli increased linearly from threshold (42-43 degrees C) to 52 degrees C. During NRM (5 units) or ipsilateral MRF stimulation (7 units), responses were inhibited such that the mean temperature-response functions were shifted toward higher temperatures with increased thresholds (1.5 degrees and 1 degree C, respectively) and reduced slopes (to 60% of control). Contralateral MRF stimulation had a similar effect in 4 units. Inhibitory effects of NRM and MRF stimulation were reduced (by greater than 25%) or abolished in 4/6 and 5/12 units, respectively, following systemic administration of the serotonin antagonist methysergide. Inhibitory effects from NRM, ipsi- and contralateral MRF were reduced or abolished in 2/9, 4/8 and 6/9 cases, respectively, following systemic administration of the noradrenergic antagonist phentolamine. These results confirm and extend previous studies of medullospinal inhibition and the role of monoamines, and are discussed in terms of analgesic mechanisms.

Action Potentials↗

Giant neurons in the rat reticular formation: a sensorimotor interface in the elementary acoustic startle circuit?

The mammalian acoustic startle response (ASR) is a relatively simple motor response that can be elicited by sudden and loud acoustic stimuli. The ASR shows several forms of plasticity, such as habituation, sensitization, and prepulse inhibition, thereby making it an interesting model for studying the underlying neuronal mechanisms. Among the neurons that compose the elementary startle circuit are giant neurons in the caudal pontine reticular nucleus (PnC), which may be good candidates for analyzing the neuronal basis of mammalian behavior. In a first step of this study, we employed retrograde and anterograde tracing techniques to identify the possible sources of input and the efferent targets of these neurons. In a second step, we performed intracellular recordings in vivo, followed by subsequent injections of HRP for morphological identification, thereby investigating whether characteristic features of the ASR are reflected by physiological properties of giant PnC neurons. Our observations demonstrate convergent, bilateral input from several auditory brainstem nuclei to the PnC, predominantly originating from neurons in the cochlear nuclear complex and the superior olivary complex. Almost no input neurons were found in the nuclei of the lateral lemniscus. As the relatively long neuronal response latencies in several of these auditory nuclei appear to be incompatible with the primary ASR, we conclude that neurons in the cochlear root nuclei most likely provide the auditory input to PnC neurons that is required to elicit the ASR. The giant PnC neurons have a remarkable number of physiological features supporting the hypothesis that they may be a neural correlate of the ASR: (1) they receive short-latency auditory input, (2) they have high firing thresholds and broad frequency tuning, (3) they are sensitive to changes in stimulus rise time and to paired-pulse stimulation, (4) repetitive acoustic stimulation results in habituation of their response, and (5) amygdaloid activity enhances their response to acoustic stimuli. Anterograde tracing showed that most giant PnC neurons are reticulospinal cells. Axon collaterals and terminal arbors were found in the reticular formation as well as in cranial and spinal motoneuron pools. The results of this study indicate that giant PnC neurons form a sensorimotor interface between the cochlear nuclear complex and cranial and spinal motoneurons. This neuronal pathway implies that the elementary acoustic startle circuit is composed of only three central relay stations and thus appears to be organized more simply than assumed in the past.

Acoustic Stimulation↗

Ketamine and MK-801 decrease acetylcholine release in the pontine reticular formation, slow breathing, and disrupt sleep.

STUDY OBJECTIVES: Ketamine induces a dissociated state of consciousness by binding to the phencyclidine binding site within the ion channel gated by the N-methyl-D-aspartate (NMDA) receptor. The brain regions and neurotransmitter systems mediating ketamine-induced alterations in arousal remain incompletely understood. This study used in vivo microdialysis to test the hypothesis that ketamine alters acetylcholine (ACh) release in the medial pontine reticular formation (mPRF). DESIGN: Acetylcholine (ACh) release, sleep, and breathing were quantified following systemic ketamine administration. Microdialysis was used to deliver the NMDA-channel blocker dizocilpine maleate (MK-801) and the R(-)-isomer of ketamine into the mPRF while measuring ACh release. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Systemically administered ketamine disrupted normal sleep-cycle organization, reduced mPRF ACh release, and significantly slowed rate of breathing. Dialysis delivery of MK-801 to the mPRF significantly decreased respiratory rate and mPRF ACh release. Dialysis delivery to the mPRF of the R(-)-ketamine isomer significantly decreased mPRF ACh release. CONCLUSIONS: Decreased mPRF ACh release caused by systemically administered ketamine was mimicked by mPRF dialysis delivery of MK-801 and the R(-)-ketamine isomer. These data are consistent with the conclusion that systemically administered ketamine may alter arousal and breathing, in part, by altering cholinergic neurotransmission in the mPRF.

Acetylcholine↗

The brainstem reticular formation is a small-world, not scale-free, network.

Recently, it has been demonstrated that several complex systems may have simple graph-theoretic characterizations as so-called 'small-world' and 'scale-free' networks. These networks have also been applied to the gross neural connectivity between primate cortical areas and the nervous system of Caenorhabditis elegans. Here, we extend this work to a specific neural circuit of the vertebrate brain--the medial reticular formation (RF) of the brainstem--and, in doing so, we have made three key contributions. First, this work constitutes the first model (and quantitative review) of this important brain structure for over three decades. Second, we have developed the first graph-theoretic analysis of vertebrate brain connectivity at the neural network level. Third, we propose simple metrics to quantitatively assess the extent to which the networks studied are small-world or scale-free. We conclude that the medial RF is configured to create small-world (implying coherent rapid-processing capabilities), but not scale-free, type networks under assumptions which are amenable to quantitative measurement.

Animals↗

Electrophysiological studies of two types of thalamo-cortical neurones and their responses to stimulation of mesencephalic reticular formation.

1. Thalamo-cortical (T-C) neurones projecting their axons to the motor cortex were recorded intra- or extra-cellularly in the anterior ventral and lateral ventral nuclear complex of the thalamus in lightly nembutalized cats. The T-C neurones were identified as responding antidromically to stimulation of the motor cortex, and were examined in connection with effects of stimulation of the centrum medianumparafascicular complex (CM), pallidum (Pal), cerebellar nuclei (CN) and mesencephalic reticular formation (RF). 2. The T-C neurones were classified into two groups, A and B. The A-group neurones responded neither to stimulation of CM nor to that of Pal. By contrast, the B-group neurones were activated from either CM, Pal or both. The effect of RF stimulation was facilitatory in many of the A-group neurones whereas it was mostly inhibitory in the B-group neurones. CN stimulation activated most of the T-C neurones in both A and B groups. 3. The A-group neurones were categorized as the deep T-C neurones mediating the deep T-C response of the cortex (the early surface-positive-deep-negative component of the augmenting response) and the B-group neurones as the superficial T-C neurones mediating the superficial T-C response of the cortex (the recruiting response and the late surface-negative-deep-positive component of the augmenting response). Desynchronization of electrocorticograms in response to RF stimulation was suggested to result from inhibition of the superficial T-C neurones and facilitation of the deep T-C neurones.

Action Potentials↗

[An increase in the excitability of nonspecific cortical formations during a decrease in the level of influences from the brain stem reticular formation].

In chronic experiments on alert unrestrained cats with cortical implanted electrodes, the thresholds of EEG activation to electrical stimulation were investigated in normal cats and in animals with diminished influences from the mesencephalic RF. Comparative analysis of the thresholds revealed an increase of the cortical unspecific excitability in diminished reticular influences. The relation of this increase to the neurophysiological mechanisms of neurotic pathology is discussed.

Animals↗

Antinociception following microinjection of dibutyryl cyclic nucleotides into the caudal reticular formation and periaqueductal gray of the rat brain.

The tail flick, paw pinch, and hot plate tests were used to assess changes in nociceptive threshold following microinjection of dibutyryl derivatives of cyclic nucleotides into areas of the central nervous system previously shown to be involved in modulation of nociceptive threshold and mediation of morphine analgesia. An elevation in the nociceptive threshold was observed on all three tests following administration of 10 micrograms dibutyryl cyclic 3':5' adenosine monophosphate (db cAMP) into the caudal brainstem reticular formation (CRF) and periaqueductal gray (PAG). Two micrograms db cAMP produced the same magnitude of analgesia but had a shorter duration of action. Twenty micrograms dibutyryl cyclic 3':5' guanosine monophosphate (db cGMP) produced analgesia on all three tests following microinjection at CRF sites but not at PAG sites. These data indicate that morphine analgesia and the antinociception produced by cyclic nucleotides may involve, at least in part, common neuronal substrates. However, the observed capacity of db cAMP to elevate nociceptive threshold does not support the hypothesis that the mechanism of morphine's analgesic action involves inhibition of adenylate cyclase.

Analgesia↗

The effect of intracerebroventricular administration of substance P fragment and met-enkephalin on the transmission of nervous impulses between the midbrain reticular formation and two generators of the hippocampal theta rhythm in rabbits.

The effect of intracerebroventricular administration of Substance P fragment and met-enkephalin on the excitability of two generators of hippocampal theta rhythm was investigated in the experiments performed on chronic rabbits. Substance P had a strong facilitatory effect on the threshold of the generator of the hippocampal theta rhythm of the frequency 4-7 c/s and an inhibitory effect on the threshold of the generator of the 7-12 c/s frequency evoked by stimulation of the midbrain reticular formation. These effects were dose dependent. The effects of met-enkephalin were opposite. They increased the threshold of the 4-7 c/s hippocampal generator and decreased the threshold of the other generator. The effect of these two compounds was evaluated according to the energy of electrical trains of pulses maintaining the continuous arousal pattern in the hippocampus.

Analgesics↗

Distribution of reticulocerebellar neurons in chicken reticular formation.

The distribution of reticulocerebellar (RC) neurons was examined by the retrograde transport of horseradish peroxidase (HRP) or wheat germ agglutinin bound to HRP (WGA-HRP) in 7 White Leghorn chickens. A large number of labeled cells were found in the nucleus reticularis pontis caudalis (RP) of the pontomedullary junction and in the nucleus reticularis gigantocellularis (Rgc), parvocellularis (Rpc), subtrigiminalis (Rst), paragigantocellularis (Rpg) and paramedianus (RpaM) in the medulla. Slightly ventral to the vestibulocochlear nerve were many large RC neurons arranged in a longitudinal manner along the lateral edge of the brainstem reticular formation (the Dorsolateral edge cells, DLe cells). RC neurons were most numerous in the Rgc and accounted for 31.9% of the total number of labeled cells, followed by RP (24.2%), Rpc (12.7%), Rpg (10.8%), RpaM (6.7%), DLe cells (6.3%) and Rst (4.9%). The great number of RC neurons was found around the levels of the vestibulocochlear nerve.

Animals↗

[Respiratory neurons in medullary reticular formation which directly project to hypoglossal motoneurons in cats].

The present study was carried out to determine the location of the excitatory premotor neurons projecting to the hypoglossal motoneurons (XII MNs) that show respiratory activities in pentobarbital-anesthetized cats. Projections from these hypoglossal premotor neurons to the phrenic motoneurons were also investigated. The following results were obtained. (1) Injection of a fluorescent dye (Fast Blue, FB) into the hypoglossal nucleus and another fluorescent dye (Nuclear Yellow, NY) into the phrenic nucleus the cells in the medullary reticular formation labelled retrogradely with FB and/or NY mainly in the region ventrolateral to the nucleus of the tractus soritarius (vl-NTS) and dorsomedial to the nucleus ambiguus (dm-AMB). (2) There were respiratory neurons in the region vl-NTS and dm-AMB which antidromically responded to the stimulation of the hypoglossal nucleus. Some of them antidromically responded also to the stimulation of the phrenic nucleus. (3) Averaging of the hypoglossal and phrenic nerve discharges by spontaneous spikes of single respiratory neurons in the region vl-NTS and dm-AMB revealed a facilitation in the hypoglossal nerve discharge. In some of these excitatory hypoglossal premotor neurons, a facilitation was also revealed in the phrenic nerve discharge. It was concluded that there were respiratory neurons in the region vl-NTS and dm-AMB which were excitatory premotor neurons projecting to the XII MNs showing respiratory activities. Some of them had excitatory projections to both the hypoglossal and phrenic motoneurons via the bifurcating axons.

Action Potentials↗