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Bicuculline-induced enhancement of sensory responses and cross-correlations between reticular formation and cortical neurons.

The visual, auditory and somatosensory responses of neurons in the brain stem reticular formation (RF) and pericruciate cortex of the cat are enhanced by intravenous administration of subconvulsant doses of bicuculline. The degree of enhancement in RF neurons is somewhat greater in magnitude and occurs in a greater percentage of RF neurons. The latency of response is shorter in the RF than in the cortex in 70% of cases. A large percentage of simultaneously recorded RF and cortical neurons which became responsive to the same stimulus exhibited consistent convulsant-induced cross-correlations of firing which were not present before drug treatment. The latency and correlation data are consistent with the possibility that the RF may subserve the cortical enhancement. Auditory response thresholds in RF neurons are reduced by bicuculline administration. Enhancement of RF neuronal responsiveness has previously been observed with several other convulsant drugs which are thought to act on different neurotransmitters suggesting that it may reflect a general action of these agents beyond the effects on specific neurotransmitters. The bicuculline-induced correlation of firing of RF and pericruciate neurons may be involved in the mechanism of initiation of convulsant-mediated seizure generalization induced by sensory stimuli.

Animals↗

Reticular formation activity during wakefulness and sleep in a hibernator (Spermophilus lateralis).

This study examined ground squirrel reticular formation (RF) cell activity as a function of: (1) arousal state, and, (2) phasic alterations in neck muscle activity. A total of 37 neurons were recorded from 11 behaving squirrels (Spermophilus lateralis). Five cells were located in the midbrain RF, 15 were in the lateral pontine site implicated in inhibition of motor output, i.e. the subcoeruleus area, 11 were in the medial pontine RF, and 6 were in the medullary RF. Regardless of location, the majority of the cells (81%; 30 of 37) exhibited greatest activity when the animals were awake and/or in rapid-eye-movement (REM) sleep. However, the relationship between neuronal activity and phasic alterations in neck muscle activity differed as a function of location. The activity of 53% of cells (8 of 15) located in the subcoeruleus area increased with phasic decreases in electromyographic (EMG) activity, whereas the activity of cells (22 of 22) in other RF sites decreased or did not change with phasic decreases in EMG activity. The increased activity of subcoeruleus area cells during phasic decreases in neck muscle activity is further evidence suggesting that the lateral pontine RF is involved in promotion of muscle atonia during REM sleep and possibly wakefulness.

Animals↗

Connections of eye-saccade-related areas within mesencephalic reticular formation with the optic tectum in goldfish.

Physiological studies demonstrate that separate sites within the mesencephalic reticular formation (MRF) can evoke eye saccades with different preferred directions. Furthermore, anatomical research suggests that a tectoreticulotectal circuit organized in accordance with the tectal eye movement map is present. However, whether the reticulotectal projection shifts with the gaze map present in the MRF is unknown. We explored this question in goldfish, by injecting biotin dextran amine within MRF sites that evoked upward, downward, oblique, and horizontal eye saccades. Then, we analyzed the labeling in the optic tectum. The main findings can be summarized as follows. 1) The MRF and the optic tectum were connected by separate axons of the tectobulbar tract. 2) The MRF was reciprocally connected mainly with the ipsilateral tectal lobe, but also with the contralateral one. 3) The MRF received projections chiefly from neurons located within intermediate and deep tectal layers. In addition, the MRF projections terminated primarily within the intermediate tectal layer. 4) The distribution of labeled neurons in the tectum shifted with the different MRF sites in a manner consistent with the tectal motor map. The area containing these cells was targeted by a high-density reticulotectal projection. In addition to this high-density topographic projection, there was a low-density one spread throughout the tectum. 5) Occasionally, boutons were observed adjacent to tectal labeled neurons. We conclude that the organization of the reticulotectal circuit is consistent with the functional topography of the MRF and that the MRF participates in a tectoreticulotectal feedback circuit.

Animals↗

Bunina bodies in neurons of the medullary reticular formation in a case of amyotrophic lateral sclerosis.

In an autopsied case of amyotrophic lateral sclerosis (ALS) with dementia (a 65-year-old man with a 4-year course) showing numerous Bunina bodies in the lower motor neurons including those of cranial motor nuclei, eosinophilic inclusions were also observed in several neurons of the reticular formation of the medulla oblongata. Some of them were confirmed to be Bunina bodies by electron microscopy. These findings indicate either that Bunina bodies can appear in neurons other than the so-called motor neurons or that the neurons in the medullary reticular formation that contain such inclusions may be lower motor neurons in the aberrant place.

Aged↗

Orienting-related eye-neck neurons of the medial ponto-bulbar reticular formation do not participate in horizontal canal-dependent vestibular reflexes of alert cats.

Ponto-bulbar reticular formation neurons, including identified reticulospinal neurons, were studied in alert, head-fixed cats. Orienting-related neurons of "eye-neck" type (ENNs) were selected on the basis of qualitative correlations of their discharges with visually triggered eye saccades and electromyographic activity (EMG) of dorsal neck muscles. It was tested whether ENNs participate both in visually triggered gaze shifts requiring eye-head coordination and in gaze-stabilizing movements, such as vestibulo-ocular and vestibulo-collic reflexes (VOR, VCR). Firing patterns were studied during passive sinusoidal rotation (0.2-1.0 Hz; 2.0-21.5 deg peak-to-peak) in the horizontal plane. Responses to electrical stimulation of the superior colliculus and the vestibular nerve were recorded to assess the convergence of tectal and vestibular synaptic inputs. The same methods were applied to a control sample of neurons with discharges apparently "unrelated" to orienting movements. ENNs did not show any modulation of firing rate correlated to compensatory VOR or VCR during passive sinusoidal rotations. Among "unrelated" cells, the fraction of modulated units was close to that reported for reticular neurons projecting in the medial reticulospinal tract. Phasic and sustained components of ENN bursts were associated with anticompensatory movements induced by rotation, such as quick phases, ocular beating field shift, and the increase of EMG activity in neck muscles acting in the direction of passive rotation. Monosynaptic excitation from the contralateral superior colliculus was observed in 92.3% of ENNs, but only 2 out of 17 tested showed an excitatory response to vestibular nerve stimulation. In the control group of "unrelated" neurons the proportions of monosynaptic tectal and excitatory vestibular nerve inputs were, respectively, 75.6 and 71.4%. It is concluded that ENNs are specifically related to active gaze shifts, derived from either visual or from head velocity inputs. Rhombencephalic connections of vestibular nuclei to these neurons appear to be quite weak. Parallel inputs from the mid- or forebrain must be assumed to explain their firing patterns during rotation-induced anticompensatory gaze shifts. Within the studied range of frequencies and amplitudes of passive rotation, ENNs did not participate in the vestibulo-collic reflex. It is therefore unlikely that reticular neurons controlling orienting eye-neck synergies act also as a premotor pathway for gaze-stabilizing movements.

Animals↗

Activity of medullary reticular formation neurons in the unrestrained cat during waking and sleep.

Single units, recorded in the medial medullary reticular formation (RF) in unrestrained, behaving cats, discharged in conjunction with specific movements and postures. Most cells were also active during REM sleep. Discharge rates in active waking and REM sleep were positively correlated and discharge patterns in these states were similar. We conclude that activity in these cells is related to the motor activation occurring in both active waking and REM sleep. We found no cells whose discharge was related in a non-specific way to motor tone or to REM sleep atonia. We discuss mechanisms by which medullary units with specific motor relations may give rise when stimulated to the relatively non-specific motor effects previously reported.

Animals↗

Interrelationship among multiunit activity of the midbrain reticular formation and lateral geniculate nucleus, thalamocortical arousal, and behavior in rats.

Analyses of multiunit activity of midbrain reticular formation (RF) and lateral geniculate nucleus (LG) revealed marked phasic covariation that conformed to characteristics of behavior. Movement patterns appeared to set the range within which RF activity and thalamocortical arousal (as reflected in LG activity) varied. In tests of spontaneous behavior, sensory stimulation, bar pressing for food, and conditioned emotional response. RF activity and thalamocortical arousal conformed to immediate properties of behavior apart from conditions giving rise to the behavior. Other analyses revealed close relationships between RF activity and visual evoked response, but only a general relationship to hippocampal slow-wave rhythms. Our findings emphasize the necessity for refining psychological conceptualizations of arousal processes.

Acoustic Stimulation↗

A nigro-rubro-bulbar pathway to the parvicellular reticular formation in the rat.

A possible pathway from the substantia nigra pars reticulata (SNr) to the parvicellular reticular formation (RFp) via the red nucleus (RN) was examined light and electron microscopically by combining anterograde and retrograde tracing techniques. After contralateral injections of biotinylated dextranamine (BDA) into the dorsolateral part of the SNr and cholera toxin B subunit (CTb) into the RFp, many CTb-labelled neurones were distributed contralaterally in the dorsal part of the RN, where numerous BDA-labelled axon terminals originating from the ipsilateral SNr were found. After contralateral injections of BDA into the dorsolateral part of the SNr and wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the RFp, ipsilateral axons labelled with BDA were found to make synaptic contacts with the somata and dendrites of contralateral neurones labelled with WGA-HRP in the dorsal part of the RN.

Animals↗

Divergent axon collaterals from fastigial oculomotor region to mesodiencephalic junction and paramedian pontine reticular formation in macaques.

Collateralization of efferent fibers from the fastigial oculomotor region (FOR) to the paramedian pontine reticular formation (PPRF) and the mesodiencephalic junction (MDJ) was studied in macaque monkeys using a fluorescent double-labeling technique. Retrogradely-labeled neurons in the contralateral FOR were examined following injections of fast blue (FB) into the MDJ and diamidino yellow (DY) into the PPRF, or vice versa. Some FOR neurons were labeled with FB, while some other FOR neurons were labeled with DY and intermingled within the FOR. While single-labeled cells in the FOR projected either to the PPRF or to the MDJ, the presence of double-labeled cells indicated that the FOR contains neurons whose axons collateralize to project to both the MDJ and PPRF. These are regarded as the preoculomotor nuclei responsible for vertical and horizontal saccades, respectively.

Animals↗

The influence of high-frequency stimulation of the midbrain reticular formation on the interaction of neurons of the neocortex.

The influence of the stimulation of the midbrain reticular formation (NRT) at a frequency of 75-100 Hz, current strength 33-400 microA, on the interaction of neurons of the visual and sensorimotor areas of the neocortex of rabbits was investigated. Cross- and autocorrelation histograms of the impulse sequences were plotted. Stimulation of the NRT led to an increase in the number of pairs of neurons functioning in correlation and an increase in the probability of discharges of neurons one after the other with delays from 100 to 400 msec as compared with resting wakefulness. The mechanisms of the interaction of the cells were not altered in the process. Comparison with previously obtained data made it possible to conclude that activation of the NRT may lead to specific changes in the interaction of neurons which are observable during pseudoconditioning and at the beginning of the development of a conditioned reflex.

Animals↗

Lateral reticular formation as a site for morphine- and clonidine-induced hypotension.

The possible role of the lateral reticular formation (LRF) in morphine-induced hypotension was investigated. Morphine (5-10 micrograms) microinjected into 15 of 25 sites in the LRF of anesthetized cats reduced mean (+/- S.E.) arterial pressure by 18.4 +/- 2.1 mmHg. Morphine applied microiontophoretically on LRF neurons had a predominately inhibitory effect on LRF cells, decreasing spontaneous rate in 51%. Since the LRF has been suggested as a site of action for clonidine-induced hypotension, clonidine was also applied microiontophoretically to these neurons. Of the cells evaluated, 43% were inhibited by clonidine. Individual cells typically responded in the same manner to morphine and clonidine. An inhibition of LRF cells by morphine and clonidine is consistent with their hypotensive action and the tonic vasopressive role assigned to the LRF. Collectively, these results suggest that the LRF is a site at which morphine and clonidine may produce their hypotensive effect.

Animals↗

Characteristics of adrenoceptors in a nociceptive pathway in the mesencephalic reticular formation of the rat.

Norepinephrine (NE) may be a neurotransmitter in a nociceptive pathway in the mesencephalic reticular formation (MRF) of the rat. When NE is applied microiontophoretically to certain neurons in rat MRF, it produces a change in neuronal firing rate similar to that produced by a noxious stimulus (foot pinch) in these neurons. If NE is a neurotransmitter involved in the transmission of nociceptive information in the MRF, specific adrenergic receptor antagonists, administered microiontophoretically, should block both the firing evoked by NE, administered microiontophoretically, and the firing evoked by foot pinch in these neurons. When phentolamine (an alpha adrenoceptor antagonist) was administered microiontophoretically it blocked the increases in neuronal firing rate evoked either by foot pinch or by NE. In contrast, propranolol (a beta adrenoceptor antagonist) rarely blocked the firing evoked by either foot pinch or by the microiontophoretic administration of NE. Thus, it appears that if NE is involved in the transmission of nociceptive information in the MRF of the rat, this information transfer is mediated by alpha adrenergic receptors.

Animals↗

Ensemble reactions of neurons in the reticular formation of the cat--categorization of inputs and temporal influences.

A method of recording ensemble reactions of reticular neurons was applied in anesthetized cats to obtain information about categorization of inputs and the influence of the time factor upon a pattern of responses, reactions to stimulus intensity changes and to complex stimuli, and temporal influences with their relation to plastic changes induced by iterative stimulation. In spite of some variability of the pattern of responses evoked in the reticular formation (RF) by electrical stimulation of the same source, reactions of the parenchyma of the RF differentiate heterotopic stimuli; reactions evoked from receptor areas situated closely to each other exhibited a similar pattern whereas less resemblance was found in the case of responses evoked from sources with a heterosegmental projection and from contralateral sources. Stimulus intensity changes did not influence substantially the pattern of recordings in the RF. The noticeable effect resulting from the increase of stimulus intensity was enlargement of responses. A complex stimulus (two heterotopic stimuli applied simultaneously) was manifested by a reaction which, in comparison with reactions evoked from each of both sources separately, had a different pattern. A trend of changes in the size of responses evoked in the RF by continuous stimulation (60 stimuli, 0.3 Hz) was observed only in some cases. Abrupt alterations of the stimulation rate (0.3 Hz in equilibrium 1 Hz, 0.3 Hz in equilibrium 2 Hz) resulted in a prompt change in responses. With constant stimulation conditions, this activity was fairly constant with an absence of trends. Persistent changes were observed only in a minority of cases. The neuronal apparatus of the RF computes ongoing effects on the basis of ability to discriminate different inputs and to readily change its function. The extent to which the RF holds information about the antecedent "history" of its functioning and the extent to which intrinsic mechanisms of the RF by itself are responsible for behavioral habituation remains problematical.

Animals↗

Interactions of morphine with putative neurotransmitters in the mesencephalic reticular formation.

Acetylcholine (ACh) and norepinephrine (NE) have been identified previously as putative nociceptive neurotransmitters in the mesencephalic reticular formation (MRF) of the rat because they frequently mimic the change in neuronal firing (usually an increase) evoked by a noxious stimulus (NS). The purpose of this study was to determine if 1.) morphine (M) acts to prevent the increase in firing evoked by a NS by blocking the effects of either of these two neurotransmitters and 2.) if this effect is a specific narcotic effect. Using the technique of microiontophoresis in conjunction with extracellular recording, we located single units in the MRF in which 1.) neuronal firing was accelerated by a NS: 2.) M blocked this response; and 3.) either ACh or NE mimicked the effect of the NS. Neurons meeting these three criteria were studied further to determine if morphine would also block the response to either of the neurotransmitters and if this was a specific narcotic effect. We found that morphine blocked the increase in neuronal firing evoked by the NS and ACh or the NS and NE in over 50% of the cells meeting the above criteria. Some neurons were found in which both ACh and NE mimicked the NS and M blocked all three responses. This blockade of these neurotransmitters was a specific narcotic effect because it could be reversed by the systemic administration of naloxone. These data lead to the tentative hypothesis that M, acting via an opiate receptor, blocks the increase in neuronal firing evoked by a NS by blocking the postsynaptic effects of either ACh or NE. This may be one of the mechanisms by which morphine acts to produce analgesia.

Acetylcholine↗

Spontaneous and artificial lesions of magnocellular reticular formation of brainstem deteriorate avoidance learning in senescence-accelerated mouse SAM.

The role of the magnocellular reticular formation (MGRF) of the brainstem on learning and memory was examined in memory-deficient mice with spontaneous spongy degeneration in the brainstem (senescence-accelerated mouse, SAMP8) and control mice (accelerated-senescence resistant mouse, SAMR 1). SAMP8 showed spontaneous age-related impairment of learning and memory, as determined by passive and active avoidance responses. The deficits of learning and memory function in passive avoidance performances began at two months of age and increased with ageing. In the brains of SAMP8 at one month of age and older, spongy degeneration was mainly observed in the brainstem, while no vacuoles were evident in SAMR1 control (normal ageing mouse) brains in the age range tested (up to 12 months). The vacuolization in SAMP8 was marked in the MGRF, especially in the dorsomedial MGRF. Quantitative analysis of the vacuolization showed that the total area and number of vacuoles in the MGRF increased with age, and they were affected by the degree of deficits in learning and memory. The latency 24 h after footshock in passive avoidance tests decreased with the increase in total area and number of vacuoles in MGRF. The number of shocks in active avoidance tests increased with the increase in total number and area of vacuoles. Thus, learning and memory ability in passive and active avoidance responses deteriorated with enlargement in the vacuolated area in MGRF, and it was assumed that MGRF (especially, the dorsomedial part) possesses functions related to learning and memory. To confirm this notion, behavior and memory tests (passive avoidance and active avoidance tests, open field tests and shock sensitivity measurements) were carried out in SAMR1 mice, whose bilateral dorsomedial MGRF was destroyed electrolytically (MGRF-lesioned mice). The MGRF-lesioned mice showed no difference from sham mice in sensory threshold or open field activity; however, there was severe deterioration in passive avoidance behavior and impairment in the active avoidance performances. From the results in SAMP8 and MGRF-lesioned mice, it was confirmed that MGRF (especially the dorsomedial part) has functions related to learning and memory, and is one part in the learning and memory system of the brain. Thus, SAMP8 can serve as a model of RF-lesioned mice with impaired learning and memory functions.

Aging↗

Diencephalic projections from the midbrain reticular formation.

(1) Physiologically guided stereotaxic coagulation was placed so as to avoid major through pathways in the midbrain reticular formation of 7 cats. Diencephalic degeneration resulting from this was traced by the Nauta method. (2) Preterminal degeneration was found in: the intralaminar nuclei and the posterior group (PO); the ventral group of thalamic nuclei; the ventral thalamus, including the zona incerta, subthalamus and fields of Forel; and the lateral hypothalamus. (3) The results are discussed in relation to somatomotor reactions, reticular influences on the electroencephalogram and telencephalic representation of pain.

Animals↗

Descending signals from the pontomedullary reticular formation are bilateral, asymmetric, and gated during reaching movements in the cat.

We examined the contribution of neurons within the pontomedullary reticular formation (PMRF) to the control of reaching movements in the cat. We recorded the activity of 127 reticular neurons, including 56 reticulospinal neurons, during movements of each forelimb; 67/127 of these neurons discharged prior to the onset of activity in the prime flexor muscles during the reach of the ipsilateral limb and form the focus of this report. Most neurons (63/67) showed similar patterns and levels of discharge activity during reaches of either limb, although activity was slightly greater during reach of the ipsilateral limb. In 26/67 cells, the initial change in discharge activity was time-locked to the go signal during reaches of either limb; we have argued that this early discharge contributes to the anticipatory postural adjustments that precede movement. In 11/26 cells, the initial change in activity was reciprocal for reaches with the left and right limbs, although activity during the movement was nonreciprocal. Spike-triggered averaging produced postspike facilitation or depression (PSD) in 12/50 cells during reaches of the limb ipsilateral to the recording site and in 17/49 cells during reach of the contralateral limb. Some cells produced PSD in ipsilateral extensor muscles before the start of the reach and during reaches made with the contralateral, but not the ipsilateral limb; this suggests the signal must be differentially gated. Overall, the results suggest a strong bilateral, albeit asymmetric, contribution from the PMRF to the control of posture and movement during voluntary movement.

Animals↗