Mesencephalic Reticular Formation Neurons Research Articles

The primate pedunculopontine nucleus region: towards a dual role in locomotion and waking state.

The mesencephalic reticular formation (MRF) mainly composed by the pedunculopontine and the cuneiform nuclei is involved in the control of several fundamental brain functions such as locomotion, rapid eye movement sleep and waking state. On the one hand, the role of MRF neurons in locomotion has been investigated for decades in different animal models, including in behaving nonhuman primate (NHP) using extracellular recordings. On the other hand, MRF neurons involved in the control of waking state have been consistently shown to constitute the cholinergic component of the reticular ascending system. However, a dual control of the locomotion and waking state by the same groups of neurons in NHP has never been demonstrated in NHP. Here, using microelectrode recordings in behaving NHP, we recorded 38 neurons in the MRF that were followed during transition between wakefulness (TWS) and sleep, i.e., until the emergence of sleep episodes characterized by typical cortical slow wave activity (SWA). We found that the MRF neurons, mainly located in the pedunculopontine nucleus region, modulated their activity during TWS with a decrease in firing rate during SWA. Of interest, we could follow some MRF neurons from locomotion to SWA and found that they also modulated their firing rate during locomotion and TWS. These new findings confirm the role of MRF neurons in both functions. They suggest that the MRF is an integration center that potentially allows to fine tune waking state and locomotor signals in order to establish an efficient locomotion.

Feed-forward and feedback projections of midbrain reticular formation neurons in the cat

Gaze changes involving the eyes and head are orchestrated by brainstem gaze centers found within the superior colliculus (SC), paramedian pontine reticular formation (PPRF), and medullary reticular formation (MdRF). The mesencephalic reticular formation (MRF) also plays a role in gaze. It receives a major input from the ipsilateral SC and contains cells that fire in relation to gaze changes. Moreover, it provides a feedback projection to the SC and feed-forward projections to the PPRF and MdRF. We sought to determine whether these MRF feedback and feed-forward projections originate from the same or different neuronal populations by utilizing paired fluorescent retrograde tracers in cats. Specifically, we tested: 1. whether MRF neurons that control eye movements form a single population by injecting the SC and PPRF with different tracers, and 2. whether MRF neurons that control head movements form a single population by injecting the SC and MdRF with different tracers. In neither case were double labeled neurons observed, indicating that feedback and feed-forward projections originate from separate MRF populations. In both cases, the labeled reticulotectal and reticuloreticular neurons were distributed bilaterally in the MRF. However, neurons projecting to the MdRF were generally constrained to the medial half of the MRF, while those projecting to the PPRF, like MRF reticulotectal neurons, were spread throughout the mediolateral axis. Thus, the medial MRF may be specialized for control of head movements, with control of eye movements being more widespread in this structure.

The Mesencephalic Reticular Formation as a Conduit for Primate Collicular Gaze Control: Tectal Inputs to Neurons Targeting the Spinal Cord and Medulla

The superior colliculus (SC), which directs orienting movements of both the eyes and head, is reciprocally connected to the mesencephalic reticular formation (MRF), suggesting the latter is involved in gaze control. The MRF has been provisionally subdivided to include a rostral portion, which subserves vertical gaze, and a caudal portion, which subserves horizontal gaze. Both regions contain cells projecting downstream that may provide a conduit for tectal signals targeting the gaze control centers which direct head movements. We determined the distribution of cells targeting the cervical spinal cord and rostral medullary reticular formation (MdRF), and investigated whether these MRF neurons receive input from the SC by the use of dual tracer techniques in Macaca fascicularis monkeys. Either biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin was injected into the SC. Wheat germ agglutinin conjugated horseradish peroxidase was placed into the ipsilateral cervical spinal cord or medial MdRF to retrogradely label MRF neurons. A small number of medially located cells in the rostral and caudal MRF were labeled following spinal cord injections, and greater numbers were labeled in the same region following MdRF injections. In both cases, anterogradely labeled tectoreticular terminals were observed in close association with retrogradely labeled neurons. These close associations between tectoreticular terminals and neurons with descending projections suggest the presence of a trans-MRF pathway that provides a conduit for tectal control over head orienting movements. The medial location of these reticulospinal and reticuloreticular neurons suggests this MRF region may be specialized for head movement control.

Contribution of the superior colliculus and the mesencephalic reticular formation to gaze control.

Converging lines of evidence support a role for the intermediate and deep layers of the superior colliculus (SC) and the mesencephalic reticular formation (MRF) in the control of combined head and eye movements (i.e., gaze). Recent microstimulation, single-cell recording, and lesion experiments are reviewed in which monkeys are free to move their heads. Cells in the SC discharge in advance of combined head and eye movements and most likely provide a gaze error signal to downstream structures. In contrast, the neurons in the MRF are of at least two types. Eye cells have features that are similar to neurons in the rostral portion of the SC, but fire before the onset of horizontal eye movments. A second group of MRF neurons begin to fire after the onset of the gaze shift and are most closely associated with movements of the head. The peak discharge of these late-onset MRF neurons occurs near the peak head velocity. Stimulation in the rostral SC generates eye movements with fixed amplitude and direction. A similar response is noted after stimulation of the more dorsal portion of the caudal MRF. Stimulation in the caudal portion of the SC produces combined head and eye movements of fixed amplitude. Electrical activation of the more ventral portions of the caudal MRF generates goal-directed and centering eye movements. Temporary inactivation of the SC with the GABA agonist muscimol generated hypometria and curved trajectories of contralateral eye movements. Inactivation of the caudal MRF produced contralateral hypermetria and ipsilateral hypometria of saccades. Release of the monkey's head demonstrated a profound contralateral head tilt. Taken together, these data suggest that the gaze signal generated in the SC is filtered by neurons in the MRF to generate a feedback signal of eye motor error. The head signal found in the MRF could cancel a portion of the gaze signal coming from the SC in the form of head velocity feedback.

Further study on 1/f fluctuations observed in central single neurons during REM sleep.

Recently, 1/f fluctuations have been discovered in the single-unit activity of mesencephalic reticular formation (MRF) neurons during REM sleep. In a previous paper, such behavior could satisfyingly be interpreted on the basis of the clustering Poisson process. The question of applicability of this model to other MRF neurons remained unanswered. The present paper reports on 1/f fluctuations in 12 MRF neurons all of which can satisfyingly be modeled by the clustering Poisson process.

An interpretation of 1/f fluctuations in neuronal spike trains during dream sleep.

The mesencephalic reticular formation (MRF) neurons are regarded as contributing to the activation of the cerebral cortex. We have investigated the statistical characteristics of the single neuronal activity in the MRF of cat during two activated states: paradoxical sleep (PS) and state in which the animal is watching birds (BW). 1/f-like spectra are observed for both PS and BW states, being more pronounced for PS state. For the interpretation of these findings, we have applied the clustering Poisson process, which not only gives rise to a 1/f spectrum but also suggests a generation mechanism. The MRF neuronal activities in PS and BW are closely fitted by the clustering Poisson process, both in terms of power spectral density and counting statistics. These results strongly suggest that the activities of MRF neurons in PS and BW can be interpreted as the superpositions of randomly occurring clusters which consist of various number of impulses.

Involvement of mesencephalic reticular formation neurons in cat conditioned reflexes

Traditional defensive and operant food reflexes were used to investigate neuronal responses of the mesencephalic reticular formation. It was found that these neurons may be divided into different groups according to function, depending on how they respond to positive conditioning stimuli. Of the two main groups of neurons with sustained tonic reactions one is activated in response to positive acoustic conditioning stimulation; it no longer reacts to the same stimulus after extinction of the reflex, while the other only becomes involved in response to positive stimulation accompanying the initiation of movement. Neurons belonging to the second group begin to respond directly to acoustic stimulation after extinction of the conditioned reflex. Neurons of the mesencephalic reticular formation can thus exercise additional tonic ascending effects both in the production and inner inhibition of the conditioned reflex. The group of neurons with a phasic reaction, i.e., a double response (a direct response to sound and another produced by movement) displayed a drop in spontaneous activity during the shaping of inhibition of differentiation and of extinction in particular. It was found that the initial changes in the spike response of reticular formation neurons during conditioning and pseudo-conditioning are similar. There are thus grounds for stating that neurons of the mesencephalic reticular formation participate in the shaping, production, and inner inhibition of traditional and operant conditioned reflexes in a differentiated capacity rather than as a population reacting identically.

Markov-dependency and spectral analyses on spike-counts in mesencephalic reticular neurons during sleep and attentive states

Spontaneous activities of the mesencephalic reticular formation (MRF) neurons of head-restrained cats were recorded to investigate their dynamic properties during sleep and waking. The Markov-dependency and spectral analyses were performed on the time series of counts converted from the MRF spike-train. During slow-wave sleep (SWS), MRF neurons fired with low Markovian properties and had a similar spectral-density curve as white noise; during paradoxical sleep (PS), their firing pattern showed high Markovian properties owing to low-frequency fluctuations, with spectral densities inversely proportional to frequency (the1/f spectrum). During the attentive state of bird watching (BW), intermediate Markovian properties were observed. These results confirmed both the rest theory of SWS and the activation of the brain during PS from the viewpoint of dynamic information-processing. Furthermore, the activation of the brain during PS may be greater than in BW.

Masticatory rhythm generated by electrical and chemical stimulation of the mesencephalic reticular formation in the guinea pig

Repetitive electrical stimulation of the mesencephalic reticular formation (MRF) in ketamineanesthetized guinea pigs induced a rhythmical jaw movement (RJM) resembling mastication. The RJM was monitored by the multiple unit activity in the anterior digastric motoneuron pool (DIGMUA) as well as by the EMG activity simultaneously recorded from the masseter and anterior digastric muscles on both sides.The following results were obtained: 1. The RJM induced by the MRF stimulation was characterized by a large opening movement to the contralateral side than that which was induced by stimulation of the cortical masticatory area (CMA) . 2. The RJM induced from the medial MRF was accompanied by a well coordinated tongue movement, but that which was induced from the lateral MRF was accompanied by no tongue movements. 3. The cycle time of the RJM induced from the medial MRF was definitely longer than that induced from the CMA, but there was no difference between the RJM induced from the lateral MRF and that which was induced from the CMA. 4. The rhythmical activity of the masseter EMG appeared in phase bilaterally, as was that of the anterior digastric EMG. The EMG activities of both muscles appeared reciprocally during the RJM induced from the CMA, but they partially overlapped during the RJM induced from the lateral MRF. The medial MRF stimulation induced the digastric EMG activity alone. 5. After the animal was paralyzed, the MRF stimulation induced a rhythmical DIG-MUA in essentially the same pattern as before paralysis. 6. After the CMA-induced rhythmical masticatory activity (RMA) was abolished by a complete lesion of the pyramidal tract at the pontine level on both sides, the MRF stimulation could induce the same pattern of RMA as before the lesion. 7. After a precollicular postmammillary transection was performed, the MRF stimulation induced the same RJM as before the transection.Microinjectionof L-glutamate into the lateral MRF induced the same RMA as that which was induced by electrical stimulation of the same region in the MRF.It was concluded that stimulation of the MRF neurons can induce the RMA centrally with no intervention of either the upper brain including the CMA or the peripheral feedback afferents, and that the effect of MRF stimulation is mediated to the lower brain stem by a route other than the pyramidal tract. In addition, the MRF is assumed to be mainly activated from the upper brain including the feeding center in the hypothalamus as well as the limbic system.

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.

The effect of iontophoretically administered GABA and glycine on the neuronal activity of mesencephalic reticular formation.

By recording the neuron unit discharges we have observed the effect of iontophoresis of gamma amino butyric acid (GABA) and glycine on the electrical activity of three different types of neurons in mesencephalic reticular formation (MRF). The results indicated that both GABA and glycine have a significant inhibitory effect on the spontaneous discharges of all three types of neurons and the pain discharges of the “pain excitatory type” neurons, and this inhibitory effect can be abolished by their corresponding antagonists, picrotoxin and strychnine. In combination with known histochemical data the results suggest that GABA and glycine might be endogenous transmitters in MRF.

Effects of electro-acupuncture and exogenous transmitters applied microiontophoretically on pain discharges in mesencephalic reticular formation

This work was performed on 72 albino rats immobilized by tubocurarine. Our results suggest that electro-acupuncture might evoke a release of neurotransmitters including noradrenaline and 5-hydroxytryptamine at the level of mesencephalic reticular formation (MRF), so that discharges from the pain-sensitive neurons would be inhibited, the transmission of pain signals could be blocked and an analgesic effect produced. In addition, the results also suggest that, as a neurotransmitter, acetylcholine might probably participate in the transmission of pain signals in MRF and that electro-acupuncture might exert a post-synaptic inhibitory effect on the pain-sensitive neurons in MRF

Enhancement of mesencephalic reticular neuronal responses to sensory stimuli with pentylenetetrazol

The effects of pentylenetetrazol (PTZ) on the responses of mesencephalic reticular formation (MRF) neurons of the cat to visual, auditory and somatosensory stimuli have been evaluated. Subconvulsant doses of PTZ caused over 90% of MRF neurons which were previously unresponsive to any sensory stimuli to become abruptly responsive to stimuli in at least one sensory modality. Administration of PTZ also enhanced the responses of over 90% of previously responsive MRF neurons. Following termination of PTZ administration the response of these neurons gradually returned towards predrug patterns. These changes in MRF neuronal responses correlated well with the PTZ-induced changes in MRF sensory-evoked field potential changes and indicate one possible mechanism for these effects. Response attenuation (habituation) observed in MRF neurons appeared to be reversed by PTZ administration in some cases. These effects on MRF neurons may play a role in the triggering of generalized seizures by PTZ administration and may also be involved in seizure mechanisms of other convulsant drugs.

Dishabituation of Mesencephalic Reticular Neurons by Anesthetics

To determine whether neuronal firing is affected by anesthetics, the behavior of neurons in the mesencephalic reticular formation in response to repetitive somatosensory stimulation at 2/sec was studied during wakefulness and during nitrous oxide, halothane, and thiopental anesthesia in the cat. With clinical doses of the three anesthetics there were simultaneous blockades of both initial facilitation (28 of 32) and subsequent habituation (31 of 32) of the evoked responses in a majority of the mesencephalic reticular formation neurons. This dishabituation phenomenon was most prominent with thiopental and least prominent with nitrous oxide. Thus, it is suggested that progressive inactivation of not only the facilitatory process but also the inhibitory process in the neuronal activities of the mesencephalic reticular formation is associated with the so-called "anesthetic state" produced by these three anesthetics.

Statistical properties of neurons in the rat mesencephalic reticular formation.

Abstract This paper presents statistical analyses of spontaneous neuronal spike trains recorded from 26 single neurons and 9 simultaneously recorded pairs of neurons in the mesencephalic reticular formation of the rat. The single cells are divided into two categories on the basis of the overall shape of their autocorrelation histograms: Those of the so-called ’typical’ cells display an initial period of subdued firing and a more or less pronounced peak followed by a gradual decay superimposed upon which there may or may not be a low-level rhythmicity. Seventy percent of these cells exhibit a clear low-level rhythmicity including some 55% which exhibit a rhythm with a period 0.640 or 1.30 sec. The so-called ’special’ cells exhibit some pronounced temporal peculiarity quite distinct from the general pattern of the regular cells. These include cells which fire highly similar bursts of spikes at more-or-less regular intervals, and one clock-like cell which fires extremely regularly at intervals of 0.640 sec. Generally, in all cells, the fast or moderate rhythms tend to die out after several recurrences, whereas the slow rhythms seem to be sustained indefinitely. Cross-correlation histograms indicate complete independence in 4 of 9 pairs of neurons, slow rhythmic interdependence in 4 other pairs, and a strong fast interdependence in one pair.

Unit activity of bulbar raphe nuclei and reticular formation in cats.

Spontaneous activity and single unit responses of the bulbar raphe nuclei (NR) and mesencephalic reticular formation (MRF) were studied in unanesthetized cats. In addition to the general features, a number of special features of the unit activity of these two structures were discovered: a) in most cases NR neurons respond predominantly or entirely to cutaneous stimulation of 3 to 4 limbs; b) spontaneous activity (SA) of NR neurons is more regular and less variable in time than that of MRF neurons. Under the influence of various peripheral stimulations the spontaneous activity of NR neurons briefly increases in frequency without any change in firing pattern, whereas the increase in frequency of MRF neurons occurs for much longer and is accompanied by marked changes in spontaneous activity c) NR neurons respond to all peripheral stimuli used by an absolutely uniform, short and compact volley of spikes, whereas MRF neurons respond differently to each stimulus, with various numbers of spikes and different firing patterns. These peculiarities of NR unit activity are evidently attributable to its simpler synaptic organization than that of MRF.

Markov process of maintained impulse activity in central single neurons.

To clarify the stochast properties of the maintained impulse activity of the central nervous system, we proposed a measure of statistical dependency on the basis of Shannon's entropy. This measure could provide the Markov properties of the neural impulse sequences, representing the necessary and sufficient condition for the statistical dependence. The order of Markov process of the sequence is determined by the conditional entropy which is derived from the joint entropy. Here the joint entropy in the case of Gaussian process is directly related with the covariance matrix which is substituted for the matrix of the serial correlation coefficients. Therefore the condition to determine the order of Markov process is obtained by the equation of the matrices of the serial correlation coefficients. The order of Markov process of the neural impulse sequences recorded from the mesencephalic reticular formation (MRF), red nucleus (RN), and lateral geniculate nucleus (LGN) neurons has been estimated. The maintained impulse activity of the MRF and RN neurons had from the 2-nd to 4-th order Markov property, while that of the LGN had no Markov property, in the consecutive impulse sequences.

The effect of preoptic warming on the arousal system of the mesencephalic reticular formation

Local warming of the preoptic area (POA) induces sleep in dogs and cats. Arousal and wakefulness are dependent upon the activity of the mesencephalic reticular formation (MRF) and its activation by afferent sensory impulses. We tested the hypothesis that warming the POA induces sleep by inhibiting the activity of the MRF. Cats were anesthetized with chloralose and immobilized with a neuromuscular blocking agent. Radio frequency thermodes were implanted bilaterally in the POA, warming of which decreased the amplitude of potentials evoked by electrical stimulation of the forepaw in the ventromedial and dorsomedial midbrain tegmentum and periaqueductal gray matter by as much as 50%. This suggests that POA warming decreases the underlying activity of MRF neurons throughout most of the region required for wakefulness. To verify this and to test whether warming the POA influences the spontaneous activity of MRF neurons, the effects on single units were studied. Units were isolated in the ventromedial midbrain tegmentum only. Six of 19 units unequivocally responded to POA warming by decreasing their firing rates by as much as 90%. Three were driven by forepaw stimulation. POA warming decreased the driven activity of all three; it also decreased the spontaneous firing rates of the units that responded to forepaw stimulation and of three units that were not driven by forepaw stimulation. These data show that somatosensory inputs to MRF neurons drive their activity while inputs from POA thermosensitive neurons decrease their activity. Therefore, these results support the above hypothesis.

Effects of visual deafferentation on mesencephalic reticular activity in freely behaving cats

Effects of bilateral eye enucleation on maintained and evoked unit activity in the mesencephalic reticular formation (MRF) were studied in freely behaving cats. Recording of MRF units was carried out in the same way as before total visual deafferentation. Three recording conditions were classified: resting arousal, light sleep, and deep sleep. The MRF neurons initially decreased greatly, maintained discharge rates following visual deafferentation, and trended to recover their control level 1 month after deafferentation. Visual deafferentation brought about no notable change in the discharge pattern. Phasic enhancement of unit firing in deep sleep in association with bursts of phasic waves in the central visual system was still observable after deafferentation. Discharge rate and neural responsiveness of visually deafferented MRF neurons shifted between the three states in the same fashion as observed in intact neurons, i.e., light sleep → resting arousal → deep sleep in order of increasing sensitivity. After deafferentation there was much less incidence of MRF responses with longer latency although short-latency responses were well preserved. This phenomenon subsided with a lapse of time. The difference in response latency in the three states was detectable in deafferented MRF neurons. Immediately after visual deafferentation the extent of input convergence on MRF neurons tended to decrease in comparison with controls and this reduction sustained through 1 month. Visual deafferentation did not influence the sampling rate of nonresponding units in the MRF. No uniform relation between the location of units in the MRF and their maintained discharge rates was noted after visual deafferentation.

Cortical and hypothalamic influences on single neurons of mesencephalic reticular formation

1. A study of activity of mesencephalic reticular neurons has shown that different influences can converge on them. However, 20% of reticular neurons responded to none of the stimuli used. Nonresponding reticular neurons were characterized either by a high firing rate or by the exceptionally regular character of their activity. 2. Mesencephalic reticular neurons responding to stimuli were chiefly excited by corticofugal impulses from the first sensorimotor area and inhibited by influences from the lateral parts of the posterior hypothalamus. 3. In combined cortico-thalamic influences on the activity of mesencephalic reticular neurons, the dominant role is played by the hypothalamus.