Pontine Gigantocellular Tegmental Field Research Articles

Intracellular recordings of pontine medial gigantocellular tegmental field neurons in the naturally sleeping cat: behavioral state-related activity and soma size difference in order of recruitment

Intracellular recordings and neurobiotin labeling of medial pontine gigantocellular tegmental field (m-PFTG) neurons in the undrugged, naturally sleeping cat were performed to establish the relationship between soma size and membrane potential (MP) activity before and during the onset of the rapid eye movement (REM) phase of sleep. Initial recordings without labeling revealed that recorded neurons in the m-PFTG had a tonic, sustained membrane depolarization in REM sleep as compared with more polarized MP levels in slow-wave sleep (S) and phasic depolarizations in wakefulness (W) on a more polarized MP level. In neurobiotin-labeled neurons, there was a strong correlation between the soma size of m-PFTG neurons and the ‘lead time’, the time of onset relative to the beginning of REM, of a sustained increase in membrane depolarization. Thirty-nine m-PFTG neurons with soma cross-sectional areas ranging from 2098 μm 2 to 5958 μm 2 (mean value 3833.8 μm 2) were analyzed. A majority of these m-PFTG neurons showed an increase in membrane depolarization associated with depolarizing postsynaptic potentials (PSPs) and spike generation that occurred before electrographic signs of REM sleep onset, while the rest of the neurons depolarized at the beginning of or just after REM sleep onset. Our previous work had suggested that many of these m-PFTG neurons were output neurons to the spinal cord. Analysis of the onset time of sustained membrane depolarization (Leadtime MP) revealed that larger cells had a longer lead time, while analysis of the lead times for onset of sustained PSPs and action potentials (Leadtime AP) showed this measure not to be dependent on soma size, but to be rather uniform, occurring just before the onset of REM sleep. Hence recruitment time, defined as the difference between Leadtime AP and Leadtime MP, was dependent on cell soma size, implying that larger neurons may take longer to depolarize to an MP level critical for generating sustained action potentials, while smaller neurons may require less time.

Activation of noradrenergic mechanism attenuates glutamate-induced vasopressor responses in the pons and medulla of cats in vivo

1. Using anesthetized cats, the authors examined the noradrenergic modulation of the glutamate induced pressor and depressor responses in various brainstem areas, including pontine gigantocellular tegmental field (FTG), dorsomedial medulla (DM), rostral ventrolateral medulla (RVLM), and caudal ventrolateral medulla (CVLM). 2. Unilateral microinjection of L-glutamate (Glu, 3 nmol in 30 nL saline) into FTG, DM and RVLM produced an increased in systemic arterial presure (SAP) and a decrease in heart rate (HR), while into CVLM produced decreases of SAP and HR. 3. Application of norepinephrine (NE) into the pressor areas (005 to 5 nmol) did not alter the resting SAP and HR, but significantly attenauted the Glu-induced pressor response with an order of potency: FTG > DM > RVLM. In the depressor CVLM, NE alone produced a dose-dependent decrease of resting SAP and HR, but did not affect the Glu-induced depressor responses. 4. The involvement of different adrenoceptor subtypes was further investigated by application of selective adrenoceptor agonists including phenylephrine (α1), clonidine (α2), and isoproterenol (β). Responses to these agonists are similar to those elicited by NE, except that only α-adrenoceptor agonists could antagonize the Glu-induced pressor responses of the RVLM. 5. Our observations indicate that NE not only inhibits the pressor mechanisms in various brainstem areas but also elicits a direct depressor response in CVLM. These findings also suggest that NE acts more likely a neurotransmitter, rather than a modulator, in the CVLM.

Distribution of cholinergic, gabaergic and serotonergic neurons in the medial medullary reticular formation and their projections studied by cytotoxic lesions in the cat

As part of a larger study concerning the role of neurons in the medial medullary reticular formation in sleep-wake states, the distribution and projections of cholinergic, GABAergic and serotonergic neurons were studied within the lower brainstem of the cat. Cells were plotted with the aid of an image analysis system through the medullary reticular formation and raphe in adjacent sections immunostained for choline acetyltransferase, glutamic acid decarboxylase and serotonin. Immunostained fibres and varicosities were examined and quantified by microdensitometry in regions of the medulla, pons and upper spinal cord in normal and quisqualate-injected animals to assess the loss of local and distant projections following cytotoxic destruction of neurons in the medial medullary reticular formation. Choline acetyltransferase-immunoreactive neurons are unevenly and sparsely distributed, though none the less in significant numbers (estimated at ∼9080 in total), through the medial medullary reticular formation, and are present in all tegmental fields, including the gigantocellular (∼3700) and magnocellular (∼1760) rostrally and the ventral (∼3240) and paramedian (∼380) caudally, and are absent in the midline raphe. Glutamic acid decarboxylase-immunoreactive neurons are more evenly and densely distributed in large numbers (estimated at ∼18,720) through the medial medullary reticular formation, being present in the gigantocellular (∼5960), magnocellular (∼8260), ventral (∼2280) and paramedian (∼2220) tegmental fields, and are also numerous within the raphe magnus and pallidus-obscurus nuclei (∼3880). Serotonin-immunoreactive cells are sparse in the medial medullary reticular formation (estimated to total ∼1540), where they are mainly located in the magnocellular tegmental field (∼1340), and are concentrated in larger numbers within the raphe nuclei (∼8060). Cholinergic varicose fibres were moderately densely distributed through the medial medullary reticular formation, as well as through more distant lateral, rostral and caudal brainstem and upper spinal regions. After cytotoxic lesions focussed in the gigantocellular and magnocellular tegmental fields, a loss of ∼55% of the cholinergic neurons in the medial medullary reticular formation was associated with a minor decrease (∼35% in optical density measures) of local cholinergic fibres. Small and variable reductions in varicose fibres (and their optical density measures) were detected in distant structures (including the pontine lateral, gigantocellular and subcoerular tegmental fields and the caudal spinal trigeminal nucleus), that were none the less correlated with the number of intact medial medullary cholinergic cells, suggesting that these cells may project to distant brainstem targets, in addition to providing a minor proportion of the local cholinergic innervation of the medial medullary reticular formation. GABAergic terminals were highly densely distributed through the medullary reticular formation, as well as through distant brainstem and upper spinal cord regions. With destruction of$˛60% of the medial medullary GABAergic cells, there was a dramatic loss ($˛50% in optical density measures) of GABAergic terminals in the magnocellular and gigantocellular tegmental fields, that was correlated with the number of surviving GABAergic neurons in the region. No reduction of GABAergic varicosities was evident outside the zone of GABAergic cell destruction, suggesting that these cells provide primarily a local innervation to the medial medullary reticular formation and raphe nuclei. Destruction of a minority (∼30%) of the serotonergic cells that lie within the reticular formation (and variable related destruction of those within the midline raphe nuclei) was associated with reductions (≤50%) of the moderately dense local serotonergic varicose fibres and of the similarly dense distant fibres (in the medullary and pontine lateral tegmental fields, the pontine gigantocellular tegmental field, the subcoeruleus, the spinal trigeminal nucleus and ventral horn) that were correlated with the number of medullary serotonergic cells, establishing the existence of both local and distant projections of the serotonergic neurons. These results demonstrate the presence of a significant population of cholinergic neurons in the medial medullary reticular formation, which like medullary serotonergic neurons, provide a proportion of the local and distant brainstem and upper spinal cord innervation. In contrast, a large population of GABAergic neurons provides the major local GABAergic innervation to the medial medullary reticular formation and raphe, terminating around GABAergic as well as non-GABAergic cells, and may thus serve primarily to control, by disinhibition as well as inhibition, other projection neurons of the medullary reticular formation and raphe.

Morphological and electrophysiological identification of gigantocellular tegmental fied neurons with descending projections in the cat: II. Bulb

There are three different descending projections from the bulbar gigantocellular tegmental field (BFTG) in the cat, as defined by intracellular recording and intracellular horseradish peroxidase (HRP) techniques. The first pathway arises from neurons which send axons to the contralateral medial longitudinal fasciculus (cMLF neurons); cMLF neurons show excitatory postsynaptic potentials (EPSPs) after stimulation of the ipsilateral pontine gigantocellular tegmental field (PFTG). Most cMLF neurons have large ellipsoid-polygonal somata (mean, 56.8 micron), thick axons (average diameter, 3.09 microns), mostly non-spiny dendrites and dendritic fields flattened in the anteroposterior direction. No cMLF neurons with axon collaterals in the BFTG are present in the data of this study. The second pathway arises from neurons which send axons to the ipsilateral MLF (iMLF neurons); iMLF neurons show EPSPs after stimulation of the ipsilateral PFTG. Most iMLF neurons have large ellipsoid-polygonal somata (mean, 60.2 microns), thick axons (average diameter, 3.00 microns), mostly non-spiny dendrites and dendritic fields that are only slightly flattened in the anteroposterior direction. As with cMLF neurons, no iMLF neurons with axon collaterals in the BFTG are present in the data of this study. The third pathway arises from neurons that send axons directly into the ipsilateral caudal bulbar reticular formation (iBRF neurons). Most iBRF neurons have smaller ellipsoid-polygonal somata (mean, 38.6 microns), thinner axons (average diameter, 1.84 microns), mostly nonspiny dendrites, and dendritic fields that are flattened in the anteroposterior direction. In contrast to cMLF and iMLF neurons, axon collaterals are present in 73% of iBRF neurons. About half of iBRF neurons have bifurcated axon collaterals with both anterior and posterior projections, and in these neurons antidromic spike potentials are elicited by stimulation of the ipsilateral PFTG.

Cholinergic projections from the laterodorsal and pedunculopontine tegmental nuclei to the pontine gigantocellular tegmental field in the cat

This study demonstrates that the laterodoesal tegmental nucleus (LDT) and pedunculopontine tegmental nucleus (PPT) are sources of cholinergic projections to the cat pontine reticular formation gigantocellular tegmental field (PFTG). Neurons of the LDT and PPT were double-labeled utilizing choline acetyltransferase immunohistochemistry combined with retrograde transport of horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP). In the LDT the percentage of cholinergic neurons retrogradely labeled from PFTG was 10.2% ipsilaterally and 3.7% contralaterally, while in the PPT the percentages were 5.2% ipsilaterally and 1.3% contralaterally. These projections from the LDT and PPT to the PFTG were confirmed and their course delineated with anterograde labeling utilizing Phaseolus vulgaris leucoagglutinin (PHA-L) anterograde transport.

Morphological and electrophysiological identification of gigantocellular tegmental field neurons with descending projections in the cat: I. Pons

Two different descending projections from the pontine gigantocellular tegmental field (PFTG) were defined by the use of intracellular recording and intracellular horseradish peroxidase (HRP) techniques in the cat. Type I neurons (reticulospinal neurons) had antidromic spike potentials produced by stimulation of the ipsilateral medial longitudinal fasciculus (MLF) and sent axons to the ipsilateral MLF. Most type I neurons had large ellipsoidpolygonal somata (mean, 59.7 microns), thick axons (average diameter, 3.33 microns), and slightly oblate large dendritic fields. The mean anteroposterior extent of the dendritic field was 1,492 microns, the mean mediolateral extent was 1,784 microns, and the mean dorsoventral extent was 1,562 microns. There were no type I neurons with axon collaterals. In contrast, type II neurons (reticuloreticular neurons) had antidromic spike potentials produced by stimulation of the bulbar reticular formation (BRF) and sent axons directly to the BRF. In comparison with type I neurons, most type II neurons had smaller ellipsoidpolygonal somata (mean, 40.2 microns), thinner axons (average diameter, 2.32 microns), and smaller, slightly oblate dendritic fields. The mean anteroposterior extent of the dendritic field was 1,264 microns; the mean mediolateral extent was 1,511 microns; and the mean dorsoventral extent was 1,226 microns. Also in contrast to type I neurons, 36% of type II neurons had axon collaterals.

Descending projections from the gigantocellular tegmental field in the cat: Cells of origin and their brainstem and spinal cord trajectories

The trajectories and the cells of origin of the pontobulbar gigantocellular tegmental field descending pathways were studied in the cat using anterograde WGA-HRP and retrograde HRP techniques. Four main descending pathways and cells of origin were delineated: (1) Predominantly large neurons in the pontine gigantocellular tegmental field (average soma diameter = 43.4 microns) and rostral bulbar gigantocellular tegmental field (41.3 microns) gave rise to reticulospinal fibers descending in the ipsilateral medial longitudinal fasciculus and ventral funiculus and distributed in laminae V-X with an ipsilateral predominance. These were primarily large-diameter fibers. (2) Predominantly large neurons (46.9 microns) in the bulbar gigantocellular tegmental field gave rise to reticulospinal fibers descending in the contralateral medial longitudinal fasciculus and ventral funiculus. These were mainly large-diameter fibers. (3) Neurons of predominantly medium size (29.5 microns) in the pontine gigantocellular tegmental field gave rise to reticuloreticular fibers descending directly to and distributed bilaterally in the bulbar reticular formation. These were small-diameter fibers. (4) Neurons of predominantly medium size (28.9 microns) in the bulbar gigantocellular tegmental field gave rise to reticulospinal fibers descending in the ipsilateral reticular formation and lateral funiculus. These were small-diameter fibers.

Catecholamines and the sleep-wake cycle II. REM sleep

The exact role of catecholamines (CA) on REM sleep is still controversial. Lesion studies suggest that norepinephrine plays a neuromodulatory role in REM sleep. Support for this view is provided by pharmacological studies in which noradrenergic neurons are activated or inhibited. Thus, disturbances in the dynamic balance between neurochemical systems may alter the conditions under which optimal REM sleep takes place. Discrete radiofrequency lesions to the pontine giganto-cellular tegmental field (which includes the nuclei reticularis pontis oralis and caudalis and where cholinergic and cholinoceptive neurons have been described), result in the elimination of REM sleep. Circumscribed, electrolytic lesions of the locus coeruleus (IC) area, which only minimally extend beyond it, eliminate atonia and reduce PGO activity in REM sleep. Selective destruction of the LC or ascending noradrenergic axons with 6-hydroxydopamine does not result in significant changes of tonic or phasic components of desynchronized sleep. These results indicate that noradrenergic neurons are not necessary for the initiation and maintenance of REM sleep. Most probably, many of the effects attributed to noradrenergic structures are due to destruction of non-noradrenergic neurons and fibers of passage in the lesioned area. Inhibition of CA synthesis with α-methyl-p-tyrosine has resulted in conflicting effects on REM sleep, which could be related to factors other than NE depletion. Systemic administration of dopamine-β-hydroxylase inhibitors (disulfiram, diethyldithiocarbamate, FLA-63, fusaric acid) produced consistent reductions of REM sleep. However, the simultaneous increase of 5-HT and DA levels complicates the interpretation of these results. Selective pharmacological stimulation of presynaptic α-adrenergic (α2) receptors with clonidine, xylazine or α-methyl-dopa decreases REM sleep. Specific blockade of α 2-receptors with yohimbine, piperoxane or tolazoline also reduces desynchronized sleep, but increases wakefulness. In contrast, drugs with similar affinity for pre and postsynaptic (α1) adrenoceptors (phentolamine) markedly increase REM sleep. Compounds Compounds with agonistic activity at postsynaptic α-adrenergic sites (methoxamine) consistently reduce REM sleep, while derivatives with inhibitory activity restricted to these receptors (thymoxamine, prazosin) produce REM sleep increments. Results from studies where propranolol and isoproterenol were administered to laboratory animals point to an involvement of β-adrenergic mechanisms in REM sleep modulation. Although there is no direct evidence to support a dopaminergic influence upon REM sleep executive mechanisms, indirect pharmacological data suggests a neuromodulatory role for dopaminergic neurons. Direct dopaminergic agonists and antagonists show biphasic effects on REM sleep. Low dosages of apomorphine increase, while large doses decrease, REM sleep. Opposite effects are observed after the dopaminergic antagonist pimozide. These dose-dependent effects seem to be related to the activation or blockade of different receptors.

Effects of brainstem lesions on tonic immobility in the rabbit ( Oryctolagus cuniculus)

Lesions were placed in discrete brainstem areas implicated in the generation of both tonic immobility (TI) and paradoxical sleep (PS) to examine postulated state and event correspondences between these states in the rabbit. Lesions were concentrated in the region of the nucleus locus coeruleus (LC)—an area implicated in the mediation of muscular atonia during PS—but also included other reticular (pontine gigantocellular tegmental field: FTG), and nonreticular (vestibular, cerebellar, central grey, collicular) areas. Polygraphic recordings of EEG, EMG and EOG activities were taken during sleep-waking states and measures of the TI response were obtained before (1 day prior) and after (5 and 14 days) lesions were made. None of the lesions was followed by a sustained, significant variation in either frequency of induction or duration of TI. Following LC lesions, and to a lesser extent after FTG lesions, sleep patterns were fragmented, with a reduction or absence of PS and the occurrence of phasic motor activation at times when PS periods might be expected to occur. The absence of PS and persistence of TI following specific brainstem lesions indicate a fundamental difference in mechanisms underlying these states. It is suggested that a major determinant of these results is the activation of phasic activity during PS but not TI, and that the possibility remains that both states may share a common mechanism of tonic motor control.

Are the gigantocellular tegmental field neurons responsible for paradoxical sleep?

We have compared the effects of electrolytic and kainic acid lesions of the pontine gigantocellular tegmental field (FTG) upon paradoxical sleep (PS). Following bilateral electrolytic destruction of the ventrolateral part of the FTG, there was an almost total suppression of PS which lasted at least for 5 weeks. Muscular atonia was absent and ponto-geniculo-occipital (PGO) activity was reduced by 80% in the few remaining episodes of PS. Contrary to to these effects, total neuronal cell loss of the FTG induced by bilateral kainic acid injection was not followed by a significant quantitative and qualitative alteration of PS. These results indicate that the neurons located within the FTG are not critical for the generation of both phasic and tonic components of PS. Elimination of this state of sleep after electrolytic destruction of the ventrolateral pontine reticular formation can be explained by interruption of fibers connecting the region of the locus coeruleus complex and the bulbar reticular formation.

Elimination of paradoxical sleep by lesions of the pontine gigantocellular tegmental field in the cat

Bilateral lesions of the pontine gigantocellular tegmental field in the cat resulted in the complete elimination of paradoxical sleep during 3 weeks postoperative recording. The tonic muscular atonia, normally characteristic of this state, was absent. The phasic components, rapid eye movements and ponto-geniculoocipital (PGO) spikes, did not occur in association with an activated EEG, as they normally do in paradoxical sleep. In fact, PGO spikes were virtually absent immediately after the lesion and were only secondarily apparent as isolated phenomena during slow wave sleep to represent in total daily number 5% of normal the first week and 15% of normal the third week after the lesion. These results indicate that neurons whose perikarya and/or processes are located within the pontine gigantocellular tegmental field and which are not part of the noradrenaline locus coeruleus complex, are critical for paradoxical sleep.

Neuronal excitability modulation over the sleep cycle: a structural and mathematical model.

A model for control of the desynchronized phase of the sleep cycle postulates reciprocal interaction between cells in the pontine gigantocellular tegmental field (FTG cells) and cells in the nucleus locus coeruleus and nucleus subcoeruleus (LC cells). This physiological model leads to equations of the Lotka-Volterra type; the time course of activity predicted by the model is in good agreement with actual long-term recordings of FTG cells and single-cycle data for LC cells.

Time course of discharge rate changes by cat pontine brain stem neurons during sleep cycle.

Time course of discharge rate changes by cat pontine brain stem neurons during sleep cycle.J A Hobson, R W McCarley, R Freedman, and R T PivikJ A Hobson, R W McCarley, R Freedman, and R T PivikPublished Online:01 Nov 1974https://doi.org/10.1152/jn.1974.37.6.1297MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByImmune and Neuroprotective Effects of Physical Activity on the Brain in Depression26 July 2018 | Frontiers in Neuroscience, Vol. 12Firing of neurons in the preoptic/anterior hypothalamic areas in rat: its possible involvement in slow wave sleep and paradoxical sleepNeuroscience Research, Vol. 19, No. 1The effects of changing state on elicited ponto-geniculo-occipital (PGO) wavesElectroencephalography and Clinical Neurophysiology, Vol. 79, No. 5Neuronal firing in the pallidal region: firing patterns during sleep-wakefulness cycle in catsElectroencephalography and Clinical Neurophysiology, Vol. 67, No. 2Neuronal excitability control in health and disease: A neurophysiological comparison of REM sleep and epilepsyProgress in Neurobiology, Vol. 25, No. 2Site-specific enhancement and suppression of desynchronized sleep signs following cholinergic stimulation of three brainstem regionsBrain Research, Vol. 306, No. 1-2Brainstem control of the events of rem sleepProgress in Neurobiology, Vol. 22, No. 3Firing rates and patterns of midbrain reticular neurons during steady and transitional states of the sleep-waking cycle3 September 2013 | Experimental Brain Research, Vol. 46, No. 1Elimination of paradoxical sleep by lesions of the pontine gigantocellular tegmental field in the catNeuroscience Letters, Vol. 13, No. 3Duration of paradoxical sleep episodes. A quantitative and pattern analysis of reticular multi-unit activity in the catElectroencephalography and Clinical Neurophysiology, Vol. 43, No. 2Eye movement-associated discharge in brain stem neurons during desynchronized sleepBrain Research, Vol. 121, No. 1Processing of sensory informationProgress in Neurobiology, Vol. 9, No. 1-2Oscillatory activity of pontine neurons related to the regular occurence of REM bursts in the decerebrate catBrain Research, Vol. 116, No. 1Central control of posture: reciprocal discharge by two pontine neuronal groups leading to suppression of decerebrate rigidityBrain Research, Vol. 116, No. 1Visual cortical neurons influenced by the oculomotor input: Characterization of their receptive field propertiesBrain Research, Vol. 113, No. 2Brain stem neurons that fire selectively to a conditioned stimulus for shockBrain Research, Vol. 103, No. 2 More from this issue > Volume 37Issue 6November 1974Pages 1297-309 https://doi.org/10.1152/jn.1974.37.6.1297PubMed4436702History Published online 1 November 1974 Published in print 1 November 1974 Metrics