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PubMed2004

GABAA receptors inhibit acetylcholine release in cat pontine reticular formation: implications for REM sleep regulation.

This study used in vivo microdialysis in cat (n=12) to test the hypothesis that gamma aminobutyric acid A (GABAA) receptors in the pontine reticular formation (PRF) inhibit acetylcholine (ACh) release. Animals were anesthetized with halothane to hold arousal state constant. Six concentrations of the GABAA receptor antagonist bicuculline (0.03, 0.1, 0.3, 1, 3, and 10 mM) were delivered to a dialysis probe in the PRF, and endogenously released ACh was collected simultaneously. Bicuculline caused a concentration dependent increase in ACh release (maximal increase=345%; EC50=1.3 mM; r2=0.997). Co-administration of the GABAA receptor agonist muscimol prevented the bicuculline-induced increase in ACh release. In a second series of experiments, the effects of bicuculline (0.1, 0.3, 1, and 3 mM) on ACh release were examined without the use of general anesthesia. States of wakefulness, rapid-eye-movement (REM) sleep, and non-REM sleep were identified polygraphically before and during dialysis delivery of bicuculline. Higher concentrations of bicuculline (1 and 3 mM) significantly increased ACh release during wakefulness (36%), completely suppressed non-REM sleep, and increased ACh release during REM sleep (143%). The finding that ACh release in the PRF is modulated by GABAA receptors is consistent with the interpretation that inhibition of GABAergic transmission in the PRF contributes to the generation of REM sleep, in part, by increasing pontine ACh release.

Acetylcholine↗

PubMed2005

Effects of injecting GABAergic agents into the medullary reticular formation upon swallowing induced by the superior laryngeal nerve stimulation in decerebrate cats.

The purpose of this study was to elucidate the role of the GABAergic system in the medullary reticular formation (MRF) in the control of swallowing. In acutely decerebrated cats (n = 12), swallowing was induced by electrical stimulation (0.3-6 V at 10-20 Hz for 10-20 s every minute) applied to the superior laryngeal nerve (SLN). The stimulus intensity was adjusted so that swallowing was induced two or four times during the period of the stimulation. Bicuculline, a GABA(A) receptor antagonist, was then injected (0.10-0.15 microl, 5 mM) into the MRF through a stereotaxically placed glass micropipette. In a total of 62 injections, 19 injections (30.6%) increased the frequency of SLN-induced swallowing when it was injected into the lateral part of the MRF corresponding to the nucleus reticularis parvocellularis (NRPv). In eight of the effective injections (42.1%) which increased the frequency of SLN-induced swallowing, SLN stimulation also induced coughing. With two injections, stimulation of the SLN-induced coughing but not facilitation of swallowing. On the other hand, an injection of 0.10-0.15 microl of 5 mM muscimol, a GABA(A) receptor agonist, into the NRPv decreased the frequency of SLN-induced swallowing. These results suggest that the NRPv neurons which are responsible for evoking swallowing are under the tonic inhibitory control of the GABAergic system.

Animals↗

PubMed2004

Convulsive seizures induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid microinjection into the mesencephalic reticular formation in rats.

Effects of microinjections of a single 2 or 10 nmol dose of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) into the unilateral mesencephalic reticular formation (MRF) on behavior and on the electroencephalogram were examined in rats (n=30) over a 15-min period (Exp. 1); subsequent effects of sound stimulation with key jingling applied at 15, 30, and 45 min after the injection were observed (Exp. 2). The microinjections of a 2 nmol dose of AMPA (n=15) induced hyperactivity (15 of 15 rats) and running/circling (10 of 15 rats) in Exp. 1, and hyperactivity (5 of 15 rats) in Exp. 2. Moreover, the microinjections of a 10 nmol dose of AMPA (n=15) induced hyperactivity (15 of 15 rats), running/circling (13 of 15 rats), generalized tonic-clonic seizures (GTCS) (4 of 15 rats), and amygdala kindling-like seizures (AMKS) (8 of 15 rats) in Exp. 1; electroencephalographic seizure discharges were predominantly observed in the MRF during hyperactivity, running/circling and GTCS, while those predominantly observed in the amygdala were during AMKS. In Exp. 2, hyperactivity (15 of 15 rats), running/circling (14 of 15 rats) and GTCS (6 of 15 rats) were elicited by sound stimulation, although AMKS were not. The control group of rats (n=15) which received a single dose of saline microinjection into the unilateral MRF showed no behavioral or electroencephalographic changes in both Exp. 1 and 2. These findings suggest that potentiation of excitatory amino acid neurotransmission induced by AMPA injection into the MRF plays an important role not only in the development of hyperactivity, running/circling, GTCS and AMKS, but also in the development of audiogenic seizures.

Acoustic Stimulation↗

PubMed1991

Serotoninergic and enkephalinergic cell groups in the reticular formation of the bat ray and two skates.

The distribution of cells which were immunohistochemically positive for leu-enkephalin (LENK+) or serotonin (5-HT+), two substances widely distributed in the reticular formation, was determined in two species of skates (Raja binoculata and Raja rhina) and a bat ray (Myliobatis californica). The Rajoids are closely related to the Rhinobatoids which contains Platyrhinoidis, an elasmobranch that does not have a nucleus raphe dorsalis. Myliobatis was chosen for an outgroup comparison. Most of the nuclei that were 5-HT+ were also LENK+. The greatest number of labeled cells was in the hypothalamus bordering the third ventricle and in the neurointermediate lobe of the pituitary. The mesencephalon was rich in cells in the ventral tegmental area bordering the red nucleus. In both genera, there were numerous 5-HT+ and LENK+ fusiform cells paralleling the ventral surface of the metencephalon and myelencephalon. These cells were located in several reticular nuclei but were especially prominent in nucleus reticularis (n.r.) pontis oralis, n.r. magnocellularis, and n.r. paragigantocellularis lateralis. The latter nucleus contained fewer LENK+ than 5-HT+ cells. In both genera, 5-HT+ and LENK+ cells were located in raphe pallidus, raphe obscurus, raphe magnus, raphe centralis superior, and raphe linearis. Minor differences in distribution of the remaining 5-HT+ and LENK+ cell groups were found, but these representative elasmobranchs lack a dorsal raphe nucleus which, in mammals, is the largest serotoninergic group.

Animals↗

PubMed1989

Effect of intracerebroventricular injection of thyrotropin-releasing hormone on the nociceptive discharges in mesencephalic reticular formation in the rat.

Extracellular recording method was used to examine the effect of thyrotropin-releasing hormone (TRH) on 71 unit discharges of pain-excited neurons (PEN) in mesencephalic reticular formation (MRF) in 58 rats. Intracerebroventricular (icv) injection of TRH (10 micrograms/10 micrograms) produced significant decrease of pain discharge rate of PEN. TRH potentiated the inhibitory effect of electroacupuncture (EA) on nociceptive discharges when application of EA at bilateral "Zusanli" was coupled with icv injection of TRH. Both of these inhibiting effects of TRH were completely offset or strikingly decreased by icv preinjection of the cholinergic M-receptor blocker atropine. The results mentioned above and the mechanism of the inhibitory effect of TRH on pain discharges were discussed in this paper.

Acupuncture Analgesia↗

PubMed1981

Role of dorsal mesencephalic reticular formation and deep layers of superior colliculus as out-put stations for turning behaviour elicited from the substantia nigra pars reticulata.

In order to investigate the role of dorsal mesencephalic reticular formation (MRF) and deep layers of superior colliculus (DLSC) as out-put areas for non-dopamine mediated behavioural functions arising in the substantia nigra, discrete unilateral kainate-lesions as well as sham-lesions were placed in the MRF and DLSC. Ten days later kainate (0.75 microgram) was microinjected into the substantia nigra pars reticulata. Lesions of MRF as well as lesions of DLSC reduced the contralateral turning induced by kainate lesions of pars reticulata ipsilateral to the MRF or DLSC lesions. The lesions of MRF were more effective than lesions of DLSC. Lesions of MRF or DLSC on the side contralateral to intranigral kainate were ineffective. The results indicate that the MRF-DLSC complex is an essential area for the expression of motor behaviour elicited from the substantia nigra.

Animals↗

PubMedDate not supplied

[The giant multipolar neurons of the reticular formation in the rat brain stem after a 14-day space flight].

The effect of a 2-week space mission on the geometry parameters of giant multipolar neurons of the brain stem reticular formation in the rats flown on board Cosmos-1887 and -2044 are studied. Compensation for a deficiency of vestibular informations from the trigeminal nerve system at the cost of an decreased length of the dendrites oriented toward primary sensory nucleus and from the vestibular system through an increase in the length of the vestibular sensory nuclei-oriented dendrites is discussed.

Animals↗

PubMed2005

Activation of the rostral pontine reticular formation increases the spinal glycine level and inhibits bladder contraction in rats.

PURPOSE: We examined the mechanism involved in the inhibition of bladder activity in rats by stimulating the rostral pontine reticular formation (RPRF) using carbachol, flavoxate and propiverine, and by analysis of amino acid levels in the lumbosacral cord. MATERIALS AND METHODS: A total of 82 female rats were anesthetized with urethane. Under isovolumetric conditions physiological saline, carbachol, flavoxate or propiverine was injected into the RPRF or intravenously. Changes in bladder activity and amino acid levels in the lumbosacral cord were examined. RESULTS: Injection of carbachol or flavoxate (0.3 microM each) into the RPRF abolished bladder contraction but there was no change after injection of physiological saline or propiverine. Intravenous injection of flavoxate or propiverine (0.1 to 10 mg/kg each) inhibited bladder contraction. Amino acid analysis revealed that injection of carbachol into the RPRF increased glutamate and glycine levels in the lumbosacral cord, while injection of flavoxate into the RPRF or intravenously caused an increase in glycine the lumbosacral cord. Injection of propiverine into the RPRF or intravenously did not influence lumbosacral cord amino acid levels. CONCLUSIONS: These results suggest that the RPRF has an important role in the inhibition of bladder contraction and carbachol or flavoxate can activate descending RPRF neurons and inhibit bladder contraction via spinal glycinergic neurons.

Animals↗

PubMed1982

Effects of peripheral stimulation on the activity of neurons in the ventral tegmental area, substantia nigra and midbrain reticular formation of rats.

Extracellular recordings were obtained from neurons in the ventral tegmental area (VTA), the substantia nigra, including the zona compacta (SNC) and the zona reticulata (SNR), and the midbrain reticular formation (FOR) of adult female albino rats anesthetized with urethane and chloral hydrate. Based on electrophysiological characteristics the neurons were divided into two types. Type I neurons, with relatively long spike durations and slow discharge rates, were confined to the VTA and SNC. Type II neurons, with shorter spike durations and faster discharge rates, were observed in the SNR and FOR as well as the VTA and SNC. The effects of foot pinch (FP), tail pinch (TP) and stimulation of the vaginal cervix (VC) on the activity of the two types of neurons were investigated. Previously it was demonstrated that FP was aversive, TP elicited locomotion, sniffing and gnawing responses and VC lordosis response, vocalization and immobility. For approximately two-thirds of the neurons the effects of the three peripheral stimuli were similar; either they were activated or suppressed. Approximately 8 percent of the neurons were suppressed by FP and TP and activated by VC whereas a similar number were activated by FP and TP and suppressed by VC. Type 1 and Type II neurons in the VTA and SN were activated and suppressed by the peripheral stimuli with suppression being the most common response to FP and TP. The results are consistent with the view that VTA and SN neurons integrate a number of central and peripheral inputs.

Action Potentials↗

PubMed2000

Generalized seizures induced by an epileptic focus in the mesencephalic reticular formation: impact on the understanding of the generalizing mechanism.

The mode of seizure propagation was studied using a generalized seizure model induced by microinjection of kainic acid (KA) into a unilateral mesencephalic reticular formation (MRF) in cats and rats. Stereotactic surgery was performed under pentobarbital anesthesia; an injection cannula was placed into a unilateral MRF, and bipolar electrodes were implanted into the MRF and the thalamus. Microinjection of KA induced generalized seizures. Focal electrical seizures were elicited in the injected site of the MRF starting 30 min after the injection. The initial clinical change during each seizure was behavioral arrest. These seizures immediately developed to generalized seizures, which were characterized by generalized tonic convulsions with short-term clonic convulsions. On EEG, each generalized seizure started at the same time in all the sites of the brain recorded. Autoradiographic study using a rat model demonstrated high glucose utilization in the MRF, bilateral thalamus, forebrain and bilateral cerebral cortices. The results demonstrated an active participation of MRF in the mechanism of generalized seizures.

Animals↗

PubMed1995

Glycine receptors in the caudal pontine reticular formation: are they important for the inhibition of the acoustic startle response?

The present paper sought to test the hypothesis that inhibitory glycine receptors (GlyRs) on giant neurons of the caudal pontine reticular formation (PnC) are involved in the inhibition of the acoustic startle response (ASR) in rats. First we provided evidence for the presence of the strychnine-sensitive inhibitory GlyR on PnC neurons by immunocytochemical labeling using an antibody against the alpha 1 subunit of the GlyR. We then measured the ASR as well as two ASR inhibiting phenomena, short-term habituation and prepulse inhibition, after microinjections of the glycine antagonist strychnine (0, 5 or 10 nmol) or the glycine agonist beta-alanine (0, 50 or 100 nmol) into the PnC. Neither strychnine nor beta-alanine had a measurable influence on any of the parameters of the ASR investigated (amplitude, short-term habituation, prepulse inhibition). In contrast, systemic injection of strychnine (1 mg/kg) markedly increased the ASR amplitude. The systemic administration of strychnine did not impair prepulse inhibition. The human 'startle disease' (hyperekplexia), an exaggerated startle response, is caused by a defect of the alpha 1 subunit of the inhibitory GlyR, but it is unclear at which site in the central nervous system this defect ultimately leads to the symptoms of hyperekplexia. Our data indicate that a blockade of the inhibitory GlyRs in the PnC does not affect the ASR of rats, suggesting that deficient GlyRs in the PnC might not be involved in the etiology of the human 'startle disease'. We conclude that the inhibitory GlyRs on PnC neurons are not necessary for the inhibition of the ASR and believe that they are involved in another behavioral context.

Animals↗

PubMed2006

Dialysis delivery of an adenosine A2A agonist into the pontine reticular formation of C57BL/6J mouse increases pontine acetylcholine release and sleep.

In vivo microdialysis in C57BL/6J (B6) mouse was used to test the hypothesis that activating adenosine A(2A) receptors in the pontine reticular formation (PRF) increases acetylcholine (ACh) release and rapid eye movement (REM) sleep. Eight concentrations of the adenosine A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; CGS) were delivered to the PRF and ACh in the PRF was quantified. ACh release was significantly increased by dialysis with 3 mum CGS and significantly decreased by dialysis with 10 and 100 microm CGS. Co-administration of the adenosine A(2A) receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385; 30 nM) blocked the CGS-induced increase in ACh release. In a second series of experiments, CGS (3 microm) was delivered by dialysis to the PRF for 2 h while recording sleep and wakefulness. CGS significantly decreased time in wakefulness (-51% in h 1; -54% in h 2), increased time in non-rapid eye movement (NREM) sleep (90% in h 1; 151% in h 2), and increased both time in REM sleep (331% in h 2) and the number of REM sleep episodes (488% in h 2). The enhancement of REM sleep is consistent with the interpretation that adenosine A(2A) receptors in the PRF of the B6 mouse contribute to REM sleep regulation, in part, by increasing ACh release in the PRF. A(2A) receptor activation may promote NREM sleep via GABAergic inhibition of arousal promoting neurons in the PRF.

Acetylcholine↗

PubMed1983

Stochastic properties of spontaneous unit discharges in somatosensory cortex and mesencephalic reticular formation during sleep-waking states.

1. We compared renewal and Markovian characteristics of neuronal discharge sequences in deeper layers (V and VI) of the somatosensory area I (SI) and the mesencephalic reticular formation (MRF) of unanesthetized cats in the following five behavioral states: active wakefulness with movements (AW), motionless quiet waking (QW), slow-wave sleep (SWS), and paradoxical sleep with and without rapid eye movements (REM-PS and non-REM-PS). 2. The profile of the pooled renewal properties for the shorter interspike-interval component predicted by the exponential tail of interval distribution during a sleep-wakefulness cycle was quite different from that for the total intervals including the longer ones; e.g., the mean rate of the SI neuronal group for the shorter interval component during SWS was as high as that during REM-PS in spite of the lowest rate for the total intervals. 3. In the SI and MRF neurons, the group mean of the degree of Markovian characteristics of the shorter intervals was much larger during AW, SWS, and REM-PS then QW and non-REM-PS, indicating that successive interspike intervals of spontaneous activity are time dependent in the AW, SWS, and REM-PS states, while they tend to be independent during QW and non-REM-PS. This tendency was more conspicuous for SI than MRF. On the other hand, the longer intervals in the five states did not contribute to the revealment of the Markov property. 4. The time-independent activities during QW and non-REM-PS were markedly similar especially for SI, suggesting that these activities may be regarded as autochthonous ones inherent to the neuron and its surrounding network under study. 5. The degree of Markovian properties was much higher in the MRF neurons than in the SI neurons during each of the states of vigilance except for AW, suggesting that the MRF neuronal group has a tonically modulated unit activity even in the absence of external stimuli.

Action Potentials↗

PubMedDate not supplied

Increase in excitability of cortical nonspecific structures in the presence of a decreased level of influences from the brainstem reticular formation.

The results of the measurement of the threshold of electrical stimulation of the cortex sufficient to elicit the EEG activation reaction in the norm and under conditions of the reduction of influences from the brainstem of the reticular formation are presented. A decrease in the thresholds was observed in those conditions which are regarded as evidence of an increase in the excitability of the nonspecific cortical formations. The increase was uneven: it was maximal in the sensorimotor and minimal in the visual cortex. It is hypothesized that the data obtained in brain preparations with a decreased level of brainstem reticular influences may be applied to the understanding of certain phenomena of neurotic pathology in its neurophysiological aspect.

Animals↗

PubMed1983

The pontine reticular formation is part of the output pathway for amphetamine- and apomorphine-induced lateral head movements: evidence from experimental lesions in the rat.

Electrolytic lesions in the caudal part of the medial pontine reticular formation (PRF) in the rat abolished apomorphine- or amphetamine-induced stereotypic lateral head movements and turning to the damaged side. Rats with unilateral PRF lesions turned and circled only to the intact side, and rats with bilateral lesions did not turn at all. PRF lesions were also effective in abolishing or reducing amphetamine-induced circling in rats with unilateral nigrostriatal bundle damage. Thus, head movements induced by dopamine agonists are added to the class of head movements mediated by the PRF. It is proposed that the decussations of the motor pathways for drug-induced turning are located between the midbrain and caudal pons.

Animals↗

PubMed1994

The mechanism of noradrenergic alpha 1 excitatory modulation of pontine reticular formation neurons.

The alpha 1 adrenergic receptor occurs in all major divisions of the CNS and is thought to play a role in all behaviors influenced by norepinephrine (NE). In the medial pontine reticular formation (mPRF), the proposed site of adrenergic enhancement of startle responses (Davis, 1984), alpha 1 agonists excite most neurons (Gerber et al., 1990). We here report that alpha 1 excitation results from a reduction of a voltage- and calcium-dependent potassium current, not previously recognized as ligand-modulated. The calcium sensitivity is suggested by its antagonism with Mg2+, Cd2+, Ba2+, low concentrations of tetraethylammonium, and charybdotoxin. The voltage sensitivity of this conductance falls within the membrane potential range critical to action potential generation. Based on this voltage sensitivity, the change in repetitive firing characteristics may be predicted according to a mathematical model of the mPRF neuronal electrophysiology. The predicted response to a 50% decrease in the phenylephrine (PE)-sensitive conductance is similar to the observed responses, with respect to both the current response under voltage-clamp conditions and alterations of the AHP and frequency/current curve. In contrast, modeling a reduction of a voltage-insensitive leak current predicts none of these changes. Thus, the noradrenergic reduction of this current depolarizes the membrane, increases the likelihood of an initial response to depolarizing input, and increases firing rate during sustained depolarization in a manner consistent with an NE role as an excitatory neuromodulator of the mPRF.

Animals↗

PubMed2004

Independent and convergent signals from the pontomedullary reticular formation contribute to the control of posture and movement during reaching in the cat.

We have addressed the nature of the postural control signals contained within the discharge activity of neurons in the pontomedullary reticular formation, including reticulospinal neurons, during a reaching task in the cat. We recorded the activity of 142 neurons during ipsilateral reaching movements that required anticipatory postural adjustments (APAs) in the supporting limbs to maintain equilibrium. Discharge activity in 82/142 (58%) neurons was significantly increased before the onset of the reach. Most of these neurons discharged either in a phasic (22/82), tonic (10/82), or phasic/tonic (41/82) pattern. In each of these 3 groups, the onset of the discharge activity in some neurons was temporally related either to the go signal or to the onset of the movement. In many neurons, one component of the discharge sequence was better related to the go signal and another to the onset of the movement. Based on our previous behavioral study during the same task, we suggest that reticular neurons in which the discharge activity is better related to the go signal contribute to the initiation of the APAs that precede the movement. Neurons in which the discharge activity is better related to the movement signal might contribute to the initiation of the movement and to the production of the postural responses that accompany that movement. Together our results suggest the existence of neurons that signal posture and movement independently and others that encode a convergent signal that contributes to the control of both posture and movement.

Animals↗

PubMedDate not supplied

[Influence of the mesencephalic reticular formation on the synchronization of cortical evoked potentials].

It has been shown in experiments on alert rabbits that evoked potentials (EP) of the visual and motor cortex to a millisecond stimulation of the midbrain reticular formation (RF) have a greater similarity (due to increased amplitude and coherence of the theta-rhythmic components) as compared with preceding background activity and evoked potentials to a photic flash. The EPs of these neocortical areas to a photic flash had a more similar form after preliminary RF stimulation. The similarity of evoked responses to stimulation of RF increased after its repeated presentations. The summate poststimulus histogram in which the responses of individual units (24 neurones) of the visual cortex to a single RF stimulation were summed up, proved to be similar in form to EP recorded on the surface of the visual cortex after a similar RF stimulation.

Animals↗