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Pontine reticular formation neurons are implicated in the neuronal network for generalized clonic seizures which is intensified by audiogenic kindling.

The caudal pontine reticular formation nucleus (cPRF) is implicated in seizure propagation to the spinal cord in several forms of generalized convulsive seizures, including audiogenic seizures (AGS). Focal microinjection studies implicate cPRF as a requisite neuronal network site subserving generalized AGS in the moderate severity substrain of genetically epilepsy-prone rats (GEPR-3s). AGS in GEPR-3s culminate in generalized clonus, but daily repetition of AGS (AGS kindling) results in an additional seizure behavior, facial and forelimb (F and F) clonus, not seen prior to kindling. This study examined cPRF neuronal firing changes and seizure behaviors during AGS in GEPR-3s. We examined extracellular cPRF neuronal responses to acoustic stimuli (12 kHz) and observed neuronal firing during AGS. cPRF neurons exhibited onset responses to acoustic stimuli before and after AGS kindling. After AGS kindling, increased neuronal firing occurred, and response latencies were prolonged. Tonic neuronal firing occurred during generalized clonus, which changed to burst firing after AGS kindling. Burst firing also occurred during F and F clonus. Increased neuronal firing and the change from tonic to burst firing suggest that AGS kindling involves increased cPRF excitability. These data support an important role for cPRF neurons in generation of generalized clonus in unkindled GEPR-3s, which is increased by AGS kindling. The increased cPRF response latency might reflect a greater role of rostral components of the AGS neuronal network in transmission of acoustic responses to cPRF. This study also suggests that cPRF neurons may be involved in F and F clonus, which was unexpected since F and F clonus is thought to originate primarily in forebrain structures.

Acoustic Stimulation↗

Single-unit activity in bulbar reticular formation during food ingestion in chronic cats.

1. Single-unit activity was recorded from 215 neurons in the medial bulbar reticular formation during the masticatory sequence, from intake to deglutition, of 3 kinds of food (cat food pellets, canned fish, and milk) in 8 chronically prepared, unanesthetized, spontaneously respiring cats with their head fixed to a stereotaxic apparatus without pain or pressure. The firing patterns were compared to the simultaneously recorded EMGs of the jaw-closing and -opening muscles and to the jaw movement. 2. Fifty neurons changed their firing patterns during mastication. Nine neurons increased and one neuron decreased or stopped firing coincident with the masticatory sequence without an apparent rhythmical modulation of frequency corresponding with the masticatory rhythm (nonphasic group). The firing pattern of the remaining 40 neurons was modulated in phase with jaw movement (phasic group); 34 neurons either showed a spike burst or attained the highest firing frequency during the jaw-opening phase (opening type), while 6 neurons did so during the jaw-closing phase (closing type). The firing patterns of each neuron were essentially the same regardless of the kind of food ingested, except for 2 opening-type neurons that showed a rhythmical burst during mastication of solid food and tonic activity during lapping milk. 3. For 16 phasic neurons, there were significant correlations between some aspects of the firing pattern and a parameter of the movement during ingestion of solid food and/or milk. With one exception, these relationships did not appear to be due to sensory feedback. 4. We detected a monosynaptic excitatory projection from 3 opening-type neurons to the anterior digastric motoneurons, and monosynaptic inhibitory projections to the temporal or masseter motoneurons from 3 other opening-type neurons, by spike-triggered averaging of the full-wave rectified EMG of the jaw-closing and -opening muscles. No monosynaptic projections from the closing-type neurons or nonphasic group neurons to either jaw-opener or -closer motoneurons were detected. 5. The instantaneous firing frequency of all 3 inhibitor premotor neurons was positively correlated with the opening velocity, and the firing of 2 was also related to the jaw displacement.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Phase-dependent responses evoked in limb muscles by stimulation of medullary reticular formation during locomotion in thalamic cats.

Electromyographic and kinematic responses of all four limbs were studied when loci within the medullary reticular formation (MRF) were stimulated (30-ms train of 0.2-ms pulses at 300 Hz, strength 35 microA) during treadmill locomotion in spontaneously walking thalamic cats. Responses could be evoked in flexor or extensor muscles of any given limb by such stimulation, depending on the time during the step cycle at which the stimulus was delivered. Stimulation normally excited flexor muscles but could either excite or inhibit extensor muscles depending on the exact position of the electrode. Excitatory responses in extensor muscles were often followed by a short period of inhibition of activity. The responses in muscles of the opposing limbs of the same girdle were, in general, reciprocally organized. For instance, a stimulus delivered during the swing phase of the ipsilateral limb normally evoked excitatory responses both in flexor muscles of that limb and in extensor muscles of the contralateral limb. The same stimulus delivered during the stance phase of the ipsilateral limb evoked excitatory responses in ipsilateral extensor muscles and in contralateral flexor muscles. Responses were also observed at the same time in fore- and hindlimbs that were well organized with respect to the locomotor cycle. Seventy-five percent of all responses occurred within 8-20 ms of the onset of the stimulus train. Responses evoked in muscles of the opposing limbs of one girdle (e.g., a flexor of one limb and an extensor of the other) had similar latencies, suggesting that the responses were synchronously organized on both sides of the body rather than one being a consequence of the other. Although the majority of responses in a given muscle were elicited during its period of activity, responses could occasionally be evoked when there was no activity in that muscle or could be absent despite activity in the muscle. The short trains of stimuli were normally potent enough to affect the limb trajectory, which reflected changes in the onset or the offset of the activity of most muscles. Thus the stimuli effectively changed both the duration of the period of activity in these muscles and the overall step cycle. Longer trains of stimuli (200 ms) markedly amplified these changes to the point of completely resetting the locomotor rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Repetitive firing properties of medial pontine reticular formation neurones of the rat recorded in vitro.

1. Intracellularly recorded neurones in nucleus reticularis pontis caudalis of the medial pontine reticular formation (mPRF) in the in vitro slice preparation were analysed for repetitive firing properties in response to intracellularly applied constant-current pulses. 2. Three neuronal classes were defined by this procedure: (1) non-burst neurones, which had only a non-burst firing pattern; (2) low-threshold burst neurones, which had either a low-threshold burst pattern or a non-burst pattern; (3) high-threshold burst neurones, which had either a high-threshold burst pattern or a non-burst pattern. 3. Histological characterization of electrophysiologically identified mPRF neurones with carboxyfluorescein showed no definite morphological difference between the first two classes. There was a trend for low-threshold burst neurones to have larger somata. 4. The low-threshold burst was generated by a slow calcium-dependent low-threshold spike, revealed in the presence of tetrodotoxin. The size of the low-threshold spike and thus the number of fast action potentials in the low-threshold burst was controlled by at least five factors including: activation; inactivation; amplitude of low-threshold conductance available to be activated; delayed outward conductance; and early transient outward conductance. 5. The non-burst pattern examined in both non-burst and low-threshold burst neurones appeared to be controlled primarily by one or more calcium-dependent potassium conductances sensitive to the removal of calcium and tetraethyl-ammonium. In the presence of tetrodotoxin (TTX), the addition of antagonists to calcium-dependent potassium current revealed a slow high-threshold calcium spike which was distinguished from the low-threshold spike by its threshold, lack of inactivation (at potentials negative to -40 mV) and insensitivity to Mg2+. A long-duration after-hyperpolarization (greater than 0.5 s) was not observed in any of these cells. 6. An early transient outward rectification sensitive to 4-aminopyridine and probably mediated by A-current was apparent in low-threshold burst and non-burst neurones and affected both the low-threshold burst and non-burst firing patterns. 7. Alteration of resting membrane potential, such as occurs in vivo during the depolarization associated with desynchronized sleep, may inactivate the low-threshold spike and the transient outward conductance responsible for the distinctive responses observed from more hyperpolarized membrane potentials and produce a more homogeneous non-burst response pattern. Membrane potential effects on intrinsic conductances thus may furnish an important mechanism for changes in mPRF neuronal responsivene

Action Potentials↗

[Correlation between bioelectrical processes of the cortex, thalamus, midbrain reticular formation during formation of a defensive conditioned reflex in rabbits].

EEG power spectra of the sensorimotor area of the neocortex, the dorsal hippocampus, midbrain reticular formation and anteroventral thalamic nucleus, as well as corresponding coherence functions and phase spectra, undergo changes during formation and performance of defensive conditioned reflex in rabbit. The conclusion is draen that in the process of conditioning a morphofunctional system of brain structures is established including the above mentioned formations. Their functional integration occurs on the basis of theta-rhythm. The execution of a conditioned act requires isorhythmicity of electrical processes within the theta-range in the studied structures and an adequate level of their excitability, which is manifested in the dominance of 6,0 c/s frequency.

Animals↗

Differential effects of methylphenidate on reticular formation and thalamic neuronal activity.

Intravenous administration of methylphenidate (1 or 2 mg/kg) markedly attenuated the unit discharge rate in the mesencephalic reticular formation of rats and cats. Concurrently this drug enhanced the neural activity in the primary sensory nuclei of the thalamus. The differential effect of methylphenidate on these two neural systems suggest a possible mechanism by which it may improve attentive processes in hyperkinesis.

Acoustic Stimulation↗

Actions of microelectrophoretically applied glucocorticoid hormones on reticular formation neurones in the rat.

The effects of microelectrophoretic application of hydrocortisone (HC) and corticosterone (CS) on single neurones of the brainstem reticular formation (RF) were investigated in rats under urethane anaesthesia. Ejecting currents generally ranged from 5 to 20nA. HC and CS behaved similarly in that they produced an excitatory effect in 26% and 24% of the neurones, respectively, an inhibition in 15% and 17% and no effect in 59% of neurones. The excitatory effects predominated in the caudal portion of the FR and the inhibitory effects in the rostral RF. The different distribution of the effects may be related to functional differences between the two RF areas.

Animals↗

Effects of intraoral mechanoreceptor stimulation on reticular formation neurones, in the rabbit.

The effects of intraoral mechanoreceptor stimulation on the firing rate of single neurones of the brain stem reticular formation (RF) were investigated in rabbits. 30% of RF neurones responded to periodontal mechanoreceptor stimulation; 16% to mucosal mechanoreceptor stimulation and 6% to both types of stimuli. Periodontal stimulation induced mainly inhibitory effects localized within the mesencephalic and rostral pontine RF. Among periodontal afferents incisors were the most widely represented. The effects of mucosal mechanoreceptor stimulation were predominant in the medullary and pontine RF and they were mainly excitatory. The present results support the hypothesis that brain stem RF neurones can be recruited into regulating mastication and biting also by stimulation of intraoral mechanoreceptors.

Action Potentials↗

Vestibular efferent neurons and catecholamine cell groups in the reticular formation of the pigeon.

This study was designed to investigate the relationship between vestibular efferent neurons and catecholamine cell groups within the reticular formation of the pigeon. Horseradish peroxidase (HRP) was injected into the endolymphatic space of one labyrinth. The brain was perfused with glyoxylic acid and serial sections were examined with a fluorescence microscope. After documentation of the location of fluorescent cells the sections were reacted for HRP with tetramethylbenzidine. Fluorescent cells were noted intermingled among the HRP-labeled vestibular efferent neurons in the nucleus reticularis pontis caudalis. No neurons were both fluorescent and HRP-positive. Fluorescent cells were also noted bilaterally in locus ceruleus, raphe nucleus, and in close proximity to the abducent, facial, hypoglossal and ambiguus nuclei.

Animals↗

Mesencephalic reticular formation lesions made after habituation training abolish long-term habituation of the acoustic startle response in rats.

Lesions to the mesencephalic reticular formation (MRF) in rats severely attenuate the acquisition of long-term habituation of the startle response when the lesions are made prior to habituation training. The present experiments extend the finding of habituation deficits to animals with MRF damage made after the animals have habituated to an auditory stimulus. Following habituation training, some animals received lesions to the MRF. The startle amplitudes of these animals immediately changed from control levels to levels indistinguishable from those of animals that never habituated across days--animals with MRF lesions made prior to habituation training. The mechanism responsible for long-term habituation appears to be a progressive increase in activity within a long-term habituation pathway extrinsic to the reflex circuit for the startle response, but the synaptic mechanisms responsible for this change are unknown.

Acoustic Stimulation↗

A presynaptic site of action within the mesencephalic reticular formation for (+)-amphetamine-induced electrocortical desynchronization.

1. Changes induced in the electrocorticogram by the bilateral perfusion of (+)-amphetamine into the mesencephalic reticular formation (MRF) have been studied in cat encéphale isolé preparations. 2. (+)-Amphetamine, applied for 5 min in the MRF, mimicked the electrocortical desynchronization induced by the perfusion of (-)-noradrenaline (NA) or (-)-alpha-methylnoradrenaline (AMNA) into the same sites. 3. Perfusion of 6-hydroxydopamine (6-OHDA) also induced desynchronization but, over the 1 h perfusion period, slow wave activity gradually returned to the electrical record. 4. Following the application of 6-OHDA the effect of (+)-amphetamine was abolished or significantly attenuated, whereas the effect of NA or AMNA was not affected. 5. The electrocortical desynchronization induced by (+)-amphetamine could be restored if its application was preceded by perfusion with NA or AMNA. 6. Fluorescence studies using AMNA indicated that 6-OHDA depleted noradrenergic nerve terminals near the cannulae tips. However, the terminals were still capable of taking up exogenously applied AMNA. 7. These results suggest that (+)-amphetamine has a presynaptic action on noradrenergic nerve terminals within the MRF.

Animals↗

Effects of ketamine on nociceptive cells in the medial medullary reticular formation of the cat.

Anatomic, physiologic and behavioral evidence suggests that the neurons in the nucleus reticularis gigantocellularis of the medial medullary reticular formation may act as a relay station for the transmission of nociceptive information from the spinal cord to higher brain centers. The nucleus reticularis gigantocellularis may also be the site of action of analgesic agents, such as ketamine hydrochloride. Utilizing extracellular microelectrodes in 23 decerebrate cats, the authors measured the effect of ketamine on neurons in the nucleus reticularis gigantocellularis that were excited by electrical stimulation of peripheral nerves. The frequency of spontaneous single-unit firing activity in the nucleus reticularis gigantocellularis was suppressed by 31 +/- 11 (mean +/- 1 SE) and by 62 +/- 7 per cent with ketamine, 1.0 and 2.5 mg/kg, iv, respectively. The frequency of evoked single-unit activity was suppressed by 57 +/- 9 and 79 +/- 5 per cent with ketamine, 1.0 and 2.5 mg/kg, respectively. Ketamine produces significant depression of single-unit activity of the cells in the nucleus reticularis gigantocellularis, suggesting that this may be an important site of its analgesic action.

Animals↗

Muscimol infusions in the brain stem reticular formation reversibly block ingestion in the awake rat.

Previous studies have localized a central pattern generator for mastication to the midline pontomedullary reticular formation (RF) based on cortically induced ororhythmic movements. The present study determined whether this same substrate mediated licking responses evoked by more natural stimuli. Licking in the awake rat was initiated either through an appetitive response to sucrose presented in a bottle or by intraoral (IO) infusions. Oral rejection responses also were obtained by IO infusions of quinine hydrochloride. Small volumes of the GABA(A) agonist muscimol bilaterally infused into the lateral medullary RF significantly reduced licking and oral rejection responses measured electromyographically from the anterior digastric and geniohyoid muscles. Other than the decrement or absence of ororhythmic activity, rats appeared normal and actively approached and probed the water bottle. The suppression was reversible and returned to baseline within 3 h. In contrast, midline infusions of muscimol did not affect licking or rejection responses. We postulate that the lateral medullary RF is an essential final common path for ingestive consummatory responses.

Administration, Oral↗

Acute effects of alcohol on photic evoked potentials of rats: lateral geniculate nucleus and reticular formation.

This study examined the effects of ethanol on photic evoked potentials recorded from the dorsal lateral geniculate nucleus (LGN) and midbrain reticular formation (MRF) of chronically implanted albino rats. Animals were given intraperitoneal injections of saline, or of 0.5, 1.0, 1.5 or 2.5 g ethanol/kg body weight on separate days. Evoked potentials were recorded at 5, 20, 40 and 60 min following injection. An early positive component recorded from each structure was depressed in amplitude by only the 2.5 g/kg alcohol dose, while the succeeding negative component was depressed by both the 1.5 and 2.5 g/kg doses. Latencies of both early components in each structure were increased by the 1.5 and 2.5 g/kg alcohol doses. Alcohol doses of 1.0-2.5 g/kg depressed the amplitude of a later positive component in the LGN (latency of 78 msec), but latency was not altered. In contrast, a late positive component in the MRF (latency of 150 msec) was both decreased in amplitude and increased in latency by only the 2.5 g/kg dose. These results on subcortical structures are discussed in relation to alcohol's effects on cortical evoked potentials.

Animals↗

Organization of the nigro-tecto-bulbar pathway to the parvicellular reticular formation: a light- and electron-microscopic study in the rat.

We examined a nigro-tecto-bulbar pathway to the parvicellular reticular formation (RFp), where many premotor neurons for orofacial motor nuclei are known to be distributed, by using a combined anterograde and retrograde tracing method. After contralateral injections of biotinylated dextranamine (BDA) into the dorsolateral part of the substantia nigra (SNr) and cholera toxin B subunit (CTb) into the RFp, overlapping distributions of BDA-labeled terminals and CTb-labeled neuronal cell bodies were found in the lateralmost part of the superior colliculus (SC) ipsilateral or contralateral to the site of BDA injection or CTb injection, respectively. After contralateral injections of BDA into the SNr and horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) injection into the RFp, ipsilateral labeled axon terminals with BDA were found to make symmetrical synaptic contacts with the somata and dendrites of contralateral labeled neurons with WGA-HRP in the lateralmost part of the SC. Furthermore, we demonstrated that BDA-labeled axon terminals were immunoreactive for GABA, by using the anterograde tracing method combined with immunohistochemistry for GABA. Thus, GABA-like immunoreactive fibers originating from the dorsolateral part of the SNr make monosynaptic contacts with the tectal neurons sending their axons to the RFp.

Animals↗

[A structural organization of the sensory projections on a reticular formation of the brain stem].

The animal experiments were performed by the cutting the sensory afferent tracts which had the projections on the reticular formation (RF) of brain stem, namely--visual, acoustic and taste tracts. Brain was investigated by methods of Marki, Nauta, Fink-Haimer. A quantitative evaluation of the voluminous fractions of neurons and gla was carried out by using "Classimat" device. Capillary density was also counted. A morphologic substrate for the conduction of the specific influences was found in form of both afferent fibers entering in brain stem and the cell groups associated with them. Between the specific brain stem and reticular structures of medulla oblongata, brain stem and midbrain (n.cuneiformis, n. tegmenti pedunculo-ponticus, n.centralis oralis and caudalis pontis, n. papillioformis, n. parabrachialis medialis and n. parvocellularis) intermediate zones were determined which were localized on the junction between sensory and reticular nuclei and had specific afferentation. Intermediate zones were also found in RF between the nuclei in both oral-caudal and mediolateral directions. An idea was formulated about the differencies in a structural organization of RF in medulla oblongata, brain stem and midrain, that were conditioned by a multicentral localization of RF functions.

Animals↗