Discharge of monkey nucleus reticularis tegmenti pontis neurons changes during saccade adaptation

Saccade accuracy is maintained by adaptive mechanisms that continually modify saccade amplitude to reduce dysmetria. Previous studies suggest that adaptation occurs upstream of the caudal fastigial nucleus (CFN), the output of the oculomotor cerebellar vermis but downstream from the superior colliculus (SC). The nucleus reticularis tegmenti pontis (NRTP) is a major source of afferents to both the oculomotor vermis and the CFN and in turn receives direct input from the SC. Here we examine the activity of NRTP neurons in four rhesus monkeys during behaviorally induced changes in saccade amplitude to assess whether their discharge might reveal adaptation mechanisms that mediate changes in saccade amplitude. During amplitude decrease adaptation (average, 22%), the gradual reduction of saccade amplitude was accompanied by an increase in the number of spikes in the burst of 19/34 neurons (56%) and no change for 15 neurons (44%). For the neurons that increased their discharge, the additional spikes were added at the beginning of the saccadic burst and adaptation also delayed the peak-firing rate in some neurons. Moreover, after amplitude reduction, the movement fields changed shape in all 15 open field neurons tested. Our data show that saccadic amplitude reduction affects the number of spikes in the burst of more than half of NRTP neurons tested, primarily by increasing burst duration not frequency. Therefore adaptive changes in saccade amplitude are reflected already at a major input to the oculomotor cerebellum.     

The cortical projection to the nucleus reticularis tegmenti pontis in the rhesus monkey

Summary The projection from the cerebral cortex to the nucleus reticularis tegmenti pontis (NRT) has been studied in the rhesus monkey with silver impregnation methods. The majority of cortical afferents to NRT arise in the precentral motor cortex (area 4), while more modest contributions come from the premotor region (area 6), the somatosensory cortex (areas 3, 1, and 2) and area 5. Very few, if any, degenerating fibres were observed in the NRT after lesions of other parts of the cortex. The cortical afferents terminate throughout NRT except in its dorsomedial part. There is a topographical arrangement so that fibres from area 6 terminate most medially in the NRT, fibres from area 5 most laterally (in the processus tegmentosus lateralis), while fibres from the motor cortex end in between and cover the largest terminal field. In addition, the projection from the motor cortex is somatotopically organized with the leg represented ventrally and the arm dorsally in the NRT. There is, however, ample overlap between the terminal regions of fibres from the various cortical areas. The results are discussed in relation to the termination of other afferent contingents to the NRT, and it is concluded that even if there is a high degree of convergence, various parts of the NRT appear not to receive identical sets of afferent inputs.     

The projection from the nucleus reticularis tegmenti pontis to the cerebellum in the rhesus monkey

Summary Following injections of horseradish peroxidase in various parts of the monkey cerebellum, the distribution of labelled cells in the nucleus reticularis tegmenti pontis (NRT) has been studied. As a rule, labelled cells are found at all rostrocaudal levels of the NRT regardless of the injection size and site. The densest projection from NRT seems to reach the vermal visual area (lobulus VII), a less dense projection supplies the anterior lobe while the paramedian lobule receives a more sparse projection than the anterior lobe. Very few labelled cells were found in the NRT after injections of crus I and II. The projection is topographically organized so that the dorsomedial part of the NRT supplies lobulus VII, a large central region sends fibres to the anterior lobe (and the cerebellar hemispheres), while the lateral extension of NRT (processus tegmentosus lateralis) is connected with the paramedian lobule.The results of the present study are compared with those of a preceding one of cortical afferents to NRT. It is concluded that the cortical areas projecting to the NRT seem likely to exert their influences on largely different parts of the cerebellum via the NRT. The present results are also discussed inrelation to termination of other afferent contingents in the NRT, and it is concluded that the NRT is not homogenous anatomically, and consequently different parts of the nucleus would be expected to play somewhat different functional roles.     

Smooth-pursuit eye-movement-related neuronal activity in macaque nucleus reticularis tegmenti pontis

Neuronal responses that were observed during smooth-pursuit eye movements were recorded from cells in rostral portions of the nucleus reticularis tegmenti pontis (rNRTP). The responses were categorized as smooth-pursuit eye velocity (78%) or eye acceleration (22%). A separate population of rNRTP cells encoded static eye position. The sensitivity to pursuit eye velocity averaged 0.81 spikes/s per degrees /s, whereas the average sensitivity to pursuit eye acceleration was 0.20 spikes/s per degrees /s(2). Of the eye-velocity cells with horizontal preferences for pursuit responses, 56% were optimally responsive to contraversive smooth-pursuit eye movements and 44% preferred ipsiversive pursuit. For cells with vertical pursuit preferences, 61% preferred upward pursuit and 39% preferred downward pursuit. The direction selectivity was broad with 50% of the maximal response amplitude observed for directions of smooth pursuit up to +/-85 degrees away from the optimal direction. The activities of some rNRTP cells were linearly related to eye position with an average sensitivity of 2.1 spikes/s per deg. In some cells, the magnitude of the response during smooth-pursuit eye movements was affected by the position of the eyes even though these cells did not encode eye position. On average, pursuit centered to one side of screen center elicited a response that was 73% of the response amplitude obtained with tracking centered at screen center. For pursuit centered on the opposite side, the average response was 127% of the response obtained at screen center. The results provide a neuronal rationale for the slow, pursuit-like eye movements evoked with rNRTP microstimulation and for the deficits in smooth-pursuit eye movements observed with ibotenic acid injection into rNRTP. More globally, the results support the notion of a frontal and supplementary eye field-rNRTP-cerebellum pathway involved with controlling smooth-pursuit eye movements.     

Effect of pharmacological inactivation of nucleus reticularis tegmenti pontis on saccadic eye movements in the monkey

The superior colliculus (SC) provides signals for the generation of saccades via a direct pathway to the brain stem burst generator (BG). In addition, it sends saccade-related activity to the BG indirectly through the cerebellum via a relay in the nucleus reticularis tegmenti pontis (NRTP). Lesions of the oculomotor vermis, lobules VIc and VII, and inactivation of the caudal fastigial nucleus, the cerebellar output nucleus to which it projects, produce saccade dysmetria but have little effect on saccade peak velocity and duration. We expected similar deficits from inactivation of the NRTP. Instead, injections as small as 80 nl into the NRTP first slowed ipsiversive saccades and then gradually reduced their amplitudes. Postinjection saccades had slower peak velocities and longer durations than preinjection saccades with similar amplitudes. Contraversive saccades retained their normal kinematics. When the gains of ipsiversive saccades to 10 degrees target steps had fallen to their lowest values (0.28 +/- 0.19; mean +/- SD; n = 10 experiments), the gains of contraversive saccades to 10 degrees target steps had decreased very little (0.82 +/- 0.11). Eventually, ipsiversive saccades did not exceed 5 degrees , even to 20 degrees target steps. Moreover, these small remaining saccades apparently were made with considerable difficulty because their latencies increased substantially. When ipsiversive saccade gain was at its lowest, the gain and kinematics of vertical saccades to 10 degrees target steps exhibited inconsistent changes. We argue that our injections did not compromise the direct SC pathway. Therefore these data suggest that the cerebellar saccade pathway does not simply modulate BG activity but is required for horizontal saccades to occur at all.     

Gaze pursuit responses in nucleus reticularis tegmenti pontis of head-unrestrained macaques

Eye-head gaze pursuit-related activity was recorded in rostral portions of the nucleus reticularis tegmenti pontis (rNRTP) in alert macaques. The head was unrestrained in the horizontal plane, and macaques were trained to pursue a moving target either with their head, with the eyes stationary in the orbits, or with their eyes, with their head voluntarily held stationary in space. Head-pursuit-related modulations in rNRTP activity were observed with some cells exhibiting increases in firing rate with increases in head-pursuit frequency. For many units, this head-pursuit response appeared to saturate at higher frequencies (>0.6 Hz). The response phase re:peak head-pursuit velocity formed a continuum, containing cells that could encode head-pursuit velocity and those encoding head-pursuit acceleration. The latter cells did not exhibit head position-related activity. Sensitivities were calculated with respect to peak head-pursuit velocity and averaged 1.8 spikes/s/deg/s. Of the cells that were tested for both head- and eye-pursuit-related activity, 86% exhibited responses to both head- and eye-pursuit and therefore carried a putative gaze-pursuit signal. For these gaze-pursuit units, the ratio of head to eye response sensitivities averaged approximately 1.4. Pursuit eccentricity seemed to affect head-pursuit response amplitude even in the absence of a head position response per se. The results indicated that rNRTP is a strong candidate for the source of an active head-pursuit signal that projects to the cerebellum, specifically to the target-velocity and gaze-velocity Purkinje cells that have been observed in vermal lobules VI and VII.     

Neuronal activity in nuclei pontis and reticularis tegmenti pontis related to forelimb movements of the monkey

The activity of the pontine nucleus (PN) neuron was recorded in 3 monkeys moving a handle alternately from start to target zones in a simple extension-flexion movement at the wrist. Of 73 PN neurons related to the task, 44 were related to movement, 19 to handle holding and 5 to both movement and holding of the handle. Of the 44 movement-related neurons, 16 were related to flexion, 22 to extension, and 6 to both. In 37 of 54 analyzed movements of the PN neurons which were related to movements, or to both movements and handle holding, the change of the activity occurred before the movement. However, in most of these cases (24/37), discharge occurred less than 100 ms earlier than the start of the movement. In the remaining one-third of movements (17/54), neurons discharged after the onset of the movement. Locations of the 73 neurons were histologically verified in the pontine nucleus. Somewhat similar observations were made of 14 cells located in the nucleus reticularis tegmenti pontis (NRTP). Considering that the majority of movement-related PN and NRTP neurons discharged immediately before or even after the onset of movement, these neurons may play a role in the execution of movement, at least of a simple movement, rather than in the initiation or planning of movement.     

Vestibular nuclear efferents to the nucleus raphe pontis, the nucleus reticularis tegmenti pontis and the nuclei pontis in the cat

The projection of the vestibular nuclei to the pontine tegmentum was investigated by means of anterograde transport of tritiated leucine. Dense patches of terminal labeling were observed in the contralateral nucleus raphe pontis and the nucleus reticularis tegmenti pontis in cases where the injection involved the medial and descending vestibular nuclei. Following injections in the superior vestibular nucleus and group Y, weaker termination, also patchlike, was observed in the same tegmental nuclei, and in addition in the dorsomedial pontine nuclei proper. The results are discussed in relation to the position of the nucleus raphe pontis and the nucleus reticularis tegmenti pontis in the oculomotor pathways.     

Responses of nucleus reticularis tegmenti pontis neurons to vestibular stimulation in the rat

Summary Forty-nine neurons were recorded in the nucleus reticularis tegmenti pontis (NRTP) during horizontal vestibular and/or optokinetic stimulation in immobilized pigmented rats. During optokinetic stimulation, the response of NRTP neurons was either unidirectional (51%) or bidirectional (49%). Histological reconstruction showed that unidirectional neurons were located in the dorsal-medial part of NRTP, and bidirectional neurons in the lateral part. All neurons exhibited a response during pure vestibular sinusoidal stimulation in the frequency range 0.025 Hz-0.2 Hz. NRTP neurons were divided into two groups according to their threshold to vestibular stimulation. Group A neurons had a low threshold, a low spontaneous activity and their firing frequency slowly increased with acceleration. Group B neurons showed opposite characteristics. Phase and gain analysis suggested that NRTP neurons carry a head velocity signal. After hemiflocculectomy, the gain of the vestibular response of contralateral NRTP neurons increased. From these data, the role of NRTP in the horizontal vestibulo-oculomotor is discussed.Supported by DGRST 79.7.1012     

Smooth-pursuit eye-movement deficits with chemical lesions in macaque nucleus reticularis tegmenti pontis.

Anatomic and neuronal recordings suggest that the nucleus reticularis tegmenti pontis (NRTP) of macaques may be a major pontine component of a cortico-ponto-cerebellar pathway that subserves the control of smooth-pursuit eye movements. The existence of such a pathway was implicated by the lack of permanent pursuit impairment after bilateral lesions in the dorsolateral pontine nucleus. To provide more direct evidence that NRTP is involved with regulating smooth-pursuit eye movements, chemical lesions were made in macaque NRTP by injecting either lidocaine or ibotenic acid. Injection sites first were identified by the recording of smooth-pursuit-related modulations in neuronal activity. The resulting lesions caused significant deficits in both the maintenance and the initiation of smooth-pursuit eye movements. After lesion formation, the gain of constant-velocity, maintained smooth-pursuit eye movements decreased, on the average, by 44%. Recovery of the ability to maintain smooth-pursuit eye movements occurred over approximately 3 days when maintained pursuit gains attained normal values. The step-ramp, "Rashbass" task was used to investigate the effects of the lesions on the initiation of smooth-pursuit eye movements. Eye accelerations averaged over the initial 80 ms of pursuit initiation were determined and found to be decremented, on the average, by 48% after the administration of ibotenic acid. Impairments in the initiation and maintenance of smooth-pursuit eye movements were directional in nature. Upward pursuit seemed to be the most vulnerable and was impaired in all cases independent of lesioning agent and type of pursuit investigated. Downward smooth pursuit seemed more resistant to the effects of chemical lesions in NRTP. Impairments in horizontal tracking were observed with examples of deficits in ipsilaterally and contralaterally directed pursuit. The results provide behavioral support for the physiologically and anatomic-based conclusion that NRTP is a component of a cortico-ponto-cerebellar circuit that presumably involves the pursuit area of the frontal eye field (FEF) and projects to ocular motor-related areas of the cerebellum. This FEF-NRTP-cerebellum path would parallel a middle and medial superior temporal cerebral cortical area-dorsolateral pontine nucleus-cerebellum pathway also known to be involved with regulating smooth-pursuit eye movements.     

Electrophysiological properties of nucleus reticularis tegmenti pontis cells: Antidromic and synaptic activation

Summary Antidromically and synaptically activated spike and synaptic potentials in the nucleus reticularis tegmenti pontis (NRTP) of the cat were recorded intracellularly. The antidromic firing of the NRTP neurone is composed of IS-SD spikes with short duration and short spike-after-hyperpolarization. Membrane resistance and firing patterns were studied by applying depolarizing and hyperpolarizing current through the recording electrode. Findings indicate that the NRTP neurone has a relatively high membrane resistance and is capable of firing at a high frequency.Single shock stimulation of the interpositus (IP) and lateral nucleus (LN) of the cerebellum, brachium conjunctivum (BC), red nucleus (RN) and cerebral peduncle (CP) induced monosynaptic EPSPs in the NRTP neurones. Superior vestibular nucleus (SVN) stimulation induced monosynaptic IPSPs. Collision tests showed that (1) NRTP neurones are activated by the axons of IP and LN neurones which travel through BC, (2) these axons also send collaterals to RN, and (3) there is convergence of cerebellar, cerebral and brain stem inputs to a single NRTP neurone.     

The projection from nucleus reticularis tegmenti pontis onto the cerebellum in the cat

Summary Following stereotactically performed lesions in nucleus reticularis tegmenti pontis (N.r.t.) degenerating fibers are traced to the contralateral N.r.t., to the pontine nuclei, through brachium pontis to restricted areas of the cerebellar nuclei and to most parts of the cerebellar cortex where they terminate in the granular layer. Most degenerating fragments are found in the contralateral half of the cerebellum with the greatest density in the vermal lobules VI and VIIA and in the flocculus.Following injections of HRP in the various cerebellar lobules labeled cells are mainly present within limited groups in the N.r.t.. Injections in vermal lobules VI-VIII B give rise to labeled cells within circumscribed areas in the dorsal and ventral parts throughout the rostrocaudal extent of the N.r.t.. In cases with injections in lobule IX or the ventral paraflocculus labeled cells are found ventrally in the rostral half of the N.r.t., while following injections in the vermal lobules I-V labeled cells are mainly found in the ventral and caudal part of the N.r.t.. Following injections in the intermediate and lateral parts of the anterior lobe, Crus I and II, the paramedian lobule and the dorsal paraflocculus labeled cells occur within groups in medial and lateral parts throughout the rostrocaudal extent of the N.r.t.. Following injections in the flocculus labeled cells are found in a very distinct group in the dorsal and rostral part of the N.r.t., While an injection in the nodulus (lobule X) gave rise to a smaller group of labeled neurons in the dorsolateral corner in the caudal part of the N.r.t.. Labeled cells within processus tegmentosus lateralis (p.t.l.) are only found following injections in lobules VI-VIIIA, Crus I and II and the dorsal paraflocculus.From what is known about afferents to the N.r.t., it is concluded that no cerebellar lobule gets information from one only of these sources via the N.r.t.. Visual information can probably be mediated from the superior colliculus via the N.r.t. to the flocculus and to a minor extent to the vermal lobules VI-VIII B, and from the pretectum via the N.r.t. to both vermal and lateral parts of the cerebellum.     

Optokinetic response of cells in the nucleus reticularis tegmenti pontis of the pigmented rabbit

Summary In immobilized pigmented rabbits anesthetized with N₂O (70%) and halothane (2–4%), extracellular spikes were recorded from neurons in the nucleus reticularis tegmenti pontis (NRTP) and their responses to optokinetic stimulation (OKS) were examined. OKS was delivered using constant-velocity (0.1–4.0°/s) movements of a random dot pattern (60° × 60°) at 0°, 45°, 90° or 135° to the horizon. With OKS delivered to the contralateral eye (n=43), the preferred directions of NRTP cells were forward (F, n = 10), backward (B, n = 7), downward (D, n = 5), and the remaining cells showed no response (N, n = 21). With OKS delivered to the ipsilateral eye (n = 43), the preferred directions were F (n = 8), B (n = 8), upward (U, n = 2), D (n= 1) and N (n = 24). The majority of cells which responded to OKS (17/22 for contralateral, and 16/19 for ipsilateral OKS) preferred the horizontal orientation. The optimum velocity ranged from 0.2 to l°/s. The results suggest that the NRTP cells mainly transfer horizontal optikinetic signals to the flocculus and control horizontal optokinetic eye movements.     

A projection from nucleus reticularis tegmenti pontis of Bechterew to the medial vestibular nucleus in rabbits

This study documents a bilateral projection from nucleus reticularis tegmenti pontis (NRTP) to the rostral aspect of the medial vestibular nucleus (MVN) in rabbits. Horseradish peroxidase injections in rostral MVN produced retrogradely labeled neurons in the caudal half of NRTP; caudal MVN injections produced negative results. This supports the hypothesis that NRTP relays visual input to the vestibular nuclei via an extracerebellar pathway (Precht and Strata 1980), and indicates the importance of examining the contributions of both direct and cerebellar-mediated visual pathways to oculomotor physiology.     

The inhibition of movement by morphine or haloperidol depends on an intact nucleus reticularis tegmenti pontis

Electrolytic damage of the nucleus reticularis tegmenti pontis (NRTP) in rats produces a form of accelerating forward locomotion, indicating that this region is part of a system that inhibits locomotion and movement. In animals with such damage, 5 mg/kg haloperidol does not block forward locomotion although it produces complete akinesia in normal rats [2]. Our present results demonstrate that doses of morphine sulfate that render normal rats completely akinetic (40, 50, or 60 mg/kg) also fail to block forward locomotion. Furthermore, 200 μg γ-aminobutyric acid applied intracranially in the region of the NRTP can reverse the akinesia produced by systemically administered haloperidol or morphine. We suggest that there are two types of akinesia—direct and indirect—and that morphine and haloperidol may produce akinesia indirectly via an inhibitory system which includes the NRTP.     

Axonal ramification of neurons in the nucleus reticularis tegmenti pontis projecting to the paramedian lobule in the rabbit cerebellum

Projections of the nucleus reticularis tegmenti pontis (NRTP) to the cerebellar paramedian lobule were examined in the rabbit by means of the double fluorescent retrograde tract-tracing method. The rabbit NRTP is composed of a medial, large part comprising zones A (dorsomedial), B (central) and C (lateral), and of a lateral, small part (the processus tegmentosus lateralis; PTL). Following unilateral injections of Fast Blue (FB) into the rostral part of the paramedian lobule (rPML) and of Diamidino Yellow (DY) into the caudal part (cPML), known to receive spinal inputs from forelimb and hindlimb, respectively, substantial numbers of single labeled neurons were found in all bilateral NRTP divisions, apart from the zone C. Most projection neurons to the PML were located in the medial and medioventral regions of the zone B. Smaller numbers of projection neurons were located in the PTL, zone A and outside the zone B among fibers of the medial lemniscus. The pattern of FB and DY labeling suggested that neurons projecting to the rPML and cPML originated in common rather than separate regions within the NRTP. In addition, a small percentage (mean 1.3%) of double FB+DY labeled neurons were detected with a clear contralateral preponderance, among single labeled FB or DY cells. In spite of the rarity, all the NRTP neurons giving rise to intralobular collateral projections can be regarded as potential sources of simultaneous modulating influences upon two functional different forelimb (rPML) and hindlimb (cPML) regions. The findings have been discussed in relation to earlier studies in other species and commented on with respect to the possible functional meaning of these projections.     

Visual and oculomotor functions of monkey subthalamic nucleus.

1. Single-unit recordings were obtained from the subthalamic nuclei of three monkeys trained to perform a series of visuooculomotor tasks. The monkeys were trained to fixate on a spot of light on the screen (fixation task). When the spot was turned off and a target spot came on, they were required to fixate on the target quickly by making a saccade. Visually guided saccades were elicited when the target came on without a time gap (saccade task). Memory-guided saccades were elicited by delivering a brief cue stimulus while the monkey was fixating; after a delay, the fixation spot was turned off and the monkey made a saccade to the remembered target (delayed saccade task). 2. Of 265 neurons tested, 95 showed spike activity that was related to some aspects of the visuooculomotor tasks, whereas 66 neurons responded to active or passive limb or body movements. The task-related activities were classified into the following categories: eye fixation-related, saccade-related, visual stimulus-related, target- and reward-related, and lever release-related. 3. Activity related to eye fixation (n = 22) consisted of a sustained spike discharge that occurred while the animal was fixating on a target light during the tasks. The activity increased after the animal started fixating on the target and abruptly ceased when the target went off. The activity was unrelated to eye position. It was not elicited during eye fixation outside the tasks. The activity decreased when the target spot was removed. 4. Activity related to saccades (n = 22) consisted of a phasic increase in spike frequency that was time locked with a saccade made during the tasks. The greatest increases occurred predominantly after saccade onset. This activity usually was unrelated to spontaneous saccades made outside the task. The changes in activity typically were optimal in one direction, generally toward the contralateral side. 5. Visual responses (n = 14) consisted of a phasic excitation in response to a visual probe stimulus or target. Response latencies usually were 70-120 ms. The receptive fields generally were centered in the contralateral hemifield, sometimes extending into the ipsilateral field. The receptive fields included the foveal region in seven neurons; most of these neurons responded best to parafoveal stimulation. Peripheral stimuli sometimes suppressed the activity of visually responsive neurons. 6. Activity related to target and reward (n = 29) consisted of sustained spike discharge that occurred only when the monkey could expect a reward by detecting the dimming of the light spot that he was fixating.(ABSTRACT TRUNCATED AT 400 WORDS)