Caudal Mesencephalic Reticular Formation Research Articles

Spike discharge characteristic of the caudal mesencephalic reticular formation and pedunculopontine nucleus in MPTP-induced primate model of Parkinson disease

The pedunculopontine nucleus (PPN) included in the caudal mesencephalic reticular formation (cMRF) plays a key role in the control of locomotion and wake state. Regarding its involvement in the neurodegenerative process observed in Parkinson disease (PD), deep brain stimulation of the PPN was proposed to treat levodopa-resistant gait disorders. However, the precise role of the cMRF in the pathophysiology of PD, particularly in freezing of gait and other non-motor symptoms is still not clear.Here, using micro electrode recording (MER) in 2 primates, we show that dopamine depletion did not alter the mean firing rate of the overall cMRF neurons, particularly the putative non-cholinergic ones, but only a decreased activity of the regular neurons sub-group (though to be the cholinergic PPN neurons). Interestingly, a significant increase in the relative proportion of cMRF neurons with a burst pattern discharge was observed after MPTP intoxication. The present results question the hypothesis of an over-inhibition of the CMRF by the basal ganglia output structures in PD. The decreased activity observed in the regular neurons could explain some non-motor symptoms in PD regarding the strong involvement of the cholinergic neurons on the modulation of the thalamo-cortical system. The increased burst activity under dopamine depletion confirms that this specific spike discharge pattern activity also observed in other basal ganglia nuclei and in different pathologies could play a mojor role in the pathophysiology of the disease and could explain several symptoms of PD including the freezing of gait. The present data will have to be replicated in a larger number of animals and will have to investigate more in details how the modification of the spike discharge of the cMRF neurons in the parkinsonian state could alter functions such as locomotion and attentional state. This will ultimely allow a better comprehension of the pathophysiology of freezing of gait.

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.

Eye movements evoked by electrical microstimulation of the mesencephalic reticular formation in goldfish

Anatomical studies in goldfish show that the tectofugal axons provide a large number of boutons within the mesencephalic reticular formation. Electrical stimulation, reversible inactivation and cell recording in the primate central mesencephalic reticular formation have suggested that it participates in the control of rapid eye movements (saccades). Moreover, the role of this tecto-recipient area in the generation of saccadic eye movements in fish is unknown. In this study we show that the electrical microstimulation of the mesencephalic reticular formation of goldfish evoked short latency saccadic eye movements in any direction (contraversive or ipsiversive, upward or downward). Movements of the eyes were usually disjunctive. Based on the location of the sites from which eye movements were evoked and the preferred saccade direction, eye movements were divided into different groups: pure vertical saccades were mainly elicited from the rostral mesencephalic reticular formation, while oblique and pure horizontal were largely evoked from middle and caudal mesencephalic reticular formation zones. The direction and amplitude of pure vertical and horizontal saccades were unaffected by initial eye position. However the amplitude, but not the direction of most oblique saccades was systematically modified by initial eye position. At the same time, the amplitude of elicited saccades did not vary in any consistent manner along either the anteroposterior, dorsoventral or mediolateral axes (i.e. there was no topographic organization of the mesencephalic reticular formation with respect to amplitude). In addition to these groups of movements, we found convergent and goal-directed saccades evoked primarily from the anterior and posterior mesencephalic reticular formation, respectively. Finally, the metric and kinetic characteristics of saccades could be manipulated by changes in the stimulation parameters. We conclude that the mesencephalic reticular formation in goldfish shares physiological functions that correspond closely with those found in mammals.

Visual orienting response in goldfish: a multidisciplinary study

The neural basis underlying the orienting response has been thoroughly studied in frontal-eyed mammals. However, in non-mammalian species, including fish, it remains almost unknown. Therefore, we studied the contribution of the optic tectum and the mesencephalic reticular formation to the performance of the orienting response in goldfish, using behavioural, physiological, and anatomical tracer techniques. The appearance of a visual stimulus (a pellet of food) in the environment of a goldfish evoked a turn of the body to reorient the line of sight. Left-tectal lobe ablation abolished the orienting turn response towards the contralateral hemifield. Electrical microstimulation of the optic tectum suggested the presence of a motor map, which is in correspondence with the overlying visual representation, as previously reported in other vertebrates. The tracer biotin-dextran amine was injected into different functionally identified tectal zones. The results showed that rostral and caudal poles of the mesencephalic reticular formation receive outflow mainly from the rostral and caudal tectal poles, respectively. This suggests that the tectal wiring with downstream structures is site-dependent. Furthermore, the electrical activation of rostral and caudal mesencephalic reticular formation revealed a different contribution to vertical and horizontal orienting eye movements. We conclude that the basic neural system coding the orienting response appears early in phylogenesis, although some specific characteristics are selected by adaptive pressure.

Connectivity of the goldfish optic tectum with the mesencephalic and rhombencephalic reticular formation.

The optic tectum of goldfish, as in other vertebrates, plays a major role in the generation of orienting movements, including eye saccades. To perform these movements, the optic tectum sends a motor command through the mesencephalic and rhombencephalic reticular formation, to the extraocular motoneurons. Furthermore, the tectal command is adjusted by a feedback signal arising from the reticular targets. Since the features of the motor command change with respect to the tectal site, the present work was devoted to determining, quantitatively, the particular reciprocal connectivity between the reticular regions and tectal sites having different motor properties. With this aim, the bidirectional tracer, biotin dextran amine, was injected into anteromedial tectal sites, where eye movements with small horizontal and large vertical components were evoked, or into posteromedial tectal sites, where eye movements with large horizontal and small vertical components were evoked. Labeled boutons and somas were then located and counted in the reticular formation. Both were more numerous in the mesencephalon than in the rhombencephalon, and ipsilaterally than contralaterally, with respect to the injection site. Furthermore, the somas showed a tendency to be located in the area containing the most dense labeling of synaptic endings. In addition, labeled boutons were often observed in close association with retrogradely stained neurons, suggesting the presence of a tectoreticular feedback circuit. Following the injection in the anteromedial tectum, most of the boutons and labeled neurons were found in the reticular formation rostral to the oculomotor nucleus. Conversely, following the injection in the posteromedial tectum, most of the boutons and neurons were also located in the caudal mesencephalic reticular formation. Finally, boutons and neurons were found in the rhombencephalic reticular formation surrounding the abducens nucleus. They were more numerous following the injection in the posteromedial tectum. These results demonstrate characteristic patterns of reciprocal connectivity between physiologically different tectal sites and the mesencephalic and rhombencephalic reticular formation. These patterns are discussed in the framework of the neural substratum that underlies the codification of orienting movements in goldfish.

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.

Effects of reversible inactivation of the primate mesencephalic reticular formation. I. Hypermetric goal-directed saccades.

Single-neuron recording and electrical microstimulation suggest three roles for the mesencephalic reticular formation (MRF) in oculomotor control: 1) saccade triggering, 2) computation of the horizontal component of saccade amplitude (a feed-forward function), and 3) feedback of an eye velocity signal from the paramedian zone of the pontine reticular formation (PPRF) to higher structures. These ideas were tested using reversible inactivation of the MRF with pressure microinjection of muscimol, a GABA(A) agonist, in four rhesus monkeys prepared for chronic single-neuron and eye movement recording. Reversible inactivation revealed two subregions of the MRF: ventral-caudal and rostral. The ventral-caudal region, which corresponds to the central MRF, the cMRF, or nucleus subcuneiformis, is the focus of this paper and is located lateral to the oculomotor nucleus and caudal to the posterior commissure (PC). Inactivation of the cMRF produced contraversive, upward saccade hypermetria. In three of eight injections, the velocity of hypermetric saccades was too fast for a given saccade amplitude, and saccade duration was shorter. The latency for initiation of most contraversive saccades was markedly reduced. Fixation was also destabilized with the development of macrosaccadic square-wave jerks that were directed toward a contraversive goal in the hypermetric direction. Spontaneous saccades collected in total darkness were also directed toward the same orbital goal, up and to the contraversive side. Three of eight muscimol injections were associated with a shift in the initial position of the eyes. A contralateral head tilt was also observed in 5 out of 8 caudal injections. All ventral-caudal injections with head tilt showed no evidence of vertical postsaccadic drift. This suggested that the observed changes in head movement and posture resulted from inactivation of the caudal MRF and not spread of the muscimol to the interstitial nucleus of Cajal (INC). Evidence of hypermetria strongly supports the idea that the ventral-caudal MRF participates in the feedback control of saccade accuracy. However, development of goal-directed eye movements, as well as a shift in the initial position following some of the cMRF injections, suggest that this region also contributes to the generation of an estimate of target or eye position coded in craniotopic coordinates. Last, the observed reduction in contraversive saccade latency and development of macrosaccadic square-wave jerks supports a role of the MRF in saccade triggering.

Intracranial studies on potential generators of some vertex auditory evoked potentials in man.

Potential generators for surface brain stem (ABSP), P200 and P300 auditory evoked potentials have been localized in patients with implanted electrodes used as an electrophysiological procedure for surgical treatment. Results suggest that surface SP and SN1-2 and components V, VI and VII of ABSP and component P3 and P300 result from specific auditory system activation, while components N1-P2 of P200 and N2-N4 of P300 result from nonspecific systems. Two subcortical generators were localized related to surface ABSP-one at the medial geniculate thalamic region (MG) related to SP and SN1 and V, VI, VII potentials, the other near the hippocampal region related to SN2. One subcortical generator related to surface N1-P2 of P200 was found near the caudal mesencephalic reticular formation, and the other two subcortical generators related to surface N2-P4 and P3 of P300 were found at the subthalamic and MG regions, respectively. Reverse polarity of some bipolar responses and lack of amplitude-latency gradients of some referential potentials at the gyrus orbitalis, rostral thalamus and anterior commissure, suggest the existence of other additional potential generators more rostrally located.

The sources of supraspinal afferents to the spinal cord in a variety of limbed reptiles. I. Reticulospinal systems.

Horseradish peroxidase was injected into various levels of the spinal cord of turtles (Pseudemys and Chrysemys), lizards (Tupinambis, Iquana, Gekko, Sauromelus, and Gerrhonotus), and a crocodilian (Caiman). The results suggest that brainstem reticulospinal projections in limbed reptiles rival mammalian reticulospinal systems in complexity. The reptilian myelencephalic reticular formation can be divided into four distinct reticulospinal nuclei. Reticularis inferior pars dorsalis (RID) contains multipolar neurons which project bilaterally to the spinal cord. Reticularis inferior pars ventralis (RIV), which is only found in lizards and crocodilians, contains fusiform neurons with horizontally running dendrites and it projects ipsilaterally to the spinal cord. Reticularis ventrolateralis (RVL), which is found only in field lizards, contains triangular neurons whose dendrites parallel the ventrolateral edge of the brainstem and it projects ipsilaterally to the spinal cord. The myelencephalic raphe (RaI) varies considerably. RaI of turtles contains large reticulospinal neurons which form a continuous population with more laterally situated RID cells. RaI of lizards contains a few small reticulospinal neurons. RaI of the crocodilian Caiman contains giant reticulospinal neurons with laterally directed dendrites. The caudal metencephalic reticular formation of reptiles can be divided into two distinct reticulospinal nuclei. Reticularis medius (RM) contains large neurons with long, ventrally directed dendrites; it projects ipsilaterally to the spinal cord. Reticularis medius pars lateralis (RML) contains small neurons with laterally directed dendrites; it projects contralaterally to the spinal cord. The rostral mesencephalic and caudal mesencephalic reticular formation of reptiles can be divided into three distinct reticulospinal nuclei. Reticularis superior pars medialis (RSM) consists mostly of small, spindle-shaped neurons which project bilaterally to the spinal cord. In the lizard Tupinambis, however, large multipolar, ipsilaterally projecting neurons are occasionally seen in RSM. Reticularis superior pars lateralis (RSL) contains large, ipsilaterally projecting neurons with long, ventrolaterally directed dendrites. SRL in lizards can be divided into a dorsomedial portion, which projects ipsilaterally to the spinal cord, and a ventrolateral portion which projects contralaterally. The locus ceruleus-subceruleus field (LC-SC) contains small spindle-shaped neurons which project bilaterally to the spinal cord. Labelled reticulospinal neurons were also observed in the rostral metencephalic raphe (RaS) of the turtle brainstem. These cells are small, spindle-shaped neurons which resemble the small cells of the adjacent RSM field.

Effects of progesterone implants in the mesencephalon of ovariectomized rats on LH and FSH release triggered by exogenous gonadal steroids.

Unilateral implantation of crystalline progesterone into the caudal mesencephalic reticular formation (MRF) of chronically ovariectomized adult rats prevents the triggering effect of exogenous gonadal steroids on LH release and does not affect the release of FSH in the same animal.

Habituation and prestimulus inhibition of the auditory startle reflex in decerebrate rats

Integrated emgs, recorded from muscles of the neck, have been used to study the auditory startle reflex in the decerebrate rat. The reflex had a mean onset latency of 11.6 msec and a mean duration of 90 msec; it was abolished by lesions in the inferior colliculus and, in some animals, lesions in the pontine or caudal mesencephalic reticular formation. It was found that the startle response, in the decerebrate animal, was habituated in a way comparable with that described in the intact animal. The size of the response was also reduced by a single preceding auditory stimulus, whether or not that stimulus was above threshold for eliciting a startle response. It therefore appears that short term habituation and prestimulus inhibition of the startle reflex are not dependent on higher regions of the central nervous system.

Mesencephalic and diencephalic afferents to the superior colliculus and periaqueductal gray substance demonstrated by retrograde axonal transport of horseradish peroxidase in the cat

The mesencephalic and diencephalic afferent connections to the superior colliculus and the central gray substance in the cat were examined by means of the retrograde transport of horseradish peroxidase (HRP). After deep collicular injections numerous labeled cells were consistently found in the parabigeminal nucleus, the mesencephalic reticular formation, substantia nigra pars reticulata, the nucleus of posterior commissure, the pretectal area, zona incerta, and the ventral nucleus of the lateral geniculate body. A smaller number of cells was found in the inferior colliculus, the nucleus of the lateral lemniscus, the central gray substance, nucleus reticularis thalami, the anterior hypothalamic area, and, in some cases, in the contralateral superior colliculus, Forel's field, and the ventromedial hypothalamic nucleus. Only the parabigeminal nucleus and the pretectal area showed labeled cells following injections in the superficial layers of the superior colliculus. In the cats submitted to injections in the central gray substance, labeled cells were consistently found in the contralateral superior colliculus, the mesencephalic reticular formation, substantia nigra pars reticulata, zona incerta and various hypothalamic areas, especially the ventromedial nucleus. In some cases, HRP-positive cells were seen in the nucleus of posterior commissure, the pretectal area, Forel's field, and nucleus reticularis thalami. A large injection in the mediodorsal part of the caudal mesencephalic reticular formation, which included the superior colliculus and the central gray substance, resulted in numerous labeled cells in nucleus reticularis thalami. The findings are discussed with respect to the suggested functional division of the superior colliculus into deep and superficial layers. Furthermore, the possible implications of labeled cells in zona incerta and the reticular thalamic nucleus are briefly discussed.

Effects of stimulation of the caudal mesencephalic reticular formation on the postcruciate cortex in cats

The effect of electrical stimulation of the dorsolateral (DL) and ventromedial (VM) zones of the caudal region of the mesencephalic reticular formation on unit activity in the lateral zone of the posterior sigmoid gyrus was investigated in cats. The mainly excitatory character of mesencephalo-cortical effects was confirmed and predominance of unitary responses with a short latent period (3–12 msec) to stimulation of VM and a longer latent period (20–25 msec) to stimulation of DL was discovered. The experiments showed interaction between VM and DL in their effects on cortical neurons, both those sensitive to somesthetic stimuli (mono-, di-, and polyvalent) and those not responding to electrical stimulation of the skin of the limbs.

Short latency induction of estrous behavior with intracerebral gonadal hormones in overiectomized rats.

In an attempt to localize the site of action of progesterone in facilitating sexual receptivity, ovariectomized rats were primed sc with 2 μg estradiol benzoate (EB) for 3 days, and on the fourth day progesterone crystals were applied directly to the brain by inserting a hormone-containing tube into chronic cannulae implanted unilaterally in the lateral and medial preoptic area (MPOA), anterior hypothalamus, ventromedial-arcuate area, or the caudal mesencephalic reticular formation (MRF). Also, in similarly primed animals bearing chronic cannulae in the MPOA or the MRF, EB was applied directly to the brain. Lordosis behavior was quantified 15, 30, 60, 90 and 120 min after progesterone application and compared to pretest values. Progesterone in the MRF significantly increased lordosis behavior in 15 min, while in the other regions progesterone had no effect even after 2 hr. To test the specificity of this response an empty tube, tubes containing cholesterol, procaine, or serotonin were similarly implanted ...

Projections from the orbital gyrus in the cat. I. To brain stem structures

AbstractDirect projections from the anterior part of the orbital gyrus and its immediate vicinity to the brain stem in the cat were investigated by means of the Nauta and Marchi methods. These experiments were carried out in an attempt to identify the anatomical substrates subserving orbital‐gyral inhibitory influences on somatic reflexes.The cortical layers of the anterior orbital gyrus and the immediately surrounding cortex were ablated unilaterally. Preterminal degeneration was found bilaterally in the spinal trigeminal nucleus. The most consoicuous degeneration occurred in the interpoler nuclei, caudal parts of the oral nuclei, and rostral portions of the caudal nuclei of the spinal trigeminal complex. Thus, degeneration was found in the trigeminal sensory nucleus from the level of the inferior olive rostrally to levels just caudal to the obex. Preterminal degeneration was also observed bilaterally in the mesencephalic reticular formation. Heavy preterminal degeneration was found in the reticular formation of the rostral midbrain and moderate degeneration was observed in the caudal mesencephalic reticular formation, the pontile reticular substance and medullary reticular nuclei.Based on these findings, the possible pathways involved in the mediation of orbital‐cortically induced inhibition on somatic reflexes were discussed.

Bladder representation in the pontine-mesencephalic reticular formation

Ablation and stimulation investigations of the rostral pons and caudal mesencephalic reticular formation of the cat have indicated an area exclusively concerned with the organization of the micturition reflex. Contrary hypothesis suggests that these effects result from nonspecific innervation of spinal cord reflex areas. An extracellular microelectrode analysis of the rostral pons has demonstrated the presence of units responding exclusively to bladder stimulation. This latter was evoked by pelvic nerve stimulation and induction of spontaneous reflex activity. Units responding to visceral stimulation were either potentiated or depressed in firing rate, the former being predominant. Convergence to somatosensory stimuli was observed. With the latter, no units were observed to be potentiated by visceral input and depressed by somatic input. Opposite effects were obtained from somatosensory stimulation of perineal and forepaw regions. Phasically active neuronal pools were found in the rostral pons responding to initiation and termination of micturition reflex activity.