Stimulation Of Reticular Formation Research Articles

Is sleep critical for lactation in rat?

Sleep deprivation is a feature shared by most studied mammals at some point during the postpartum period. Unlike the rabbit, the pig, or the human mother, sleep has been claimed as an essential state for milk ejection in mother rats, where sleep deprivation using gentle handling (GH) prevents milk ejection and pup weight gain. Though sleep deprivation is a stressful situation itself, most common methodologies used in laboratory animals, including GH, usually involve aversive stimulus to prevent sleep, adding further stress to the animal. Deep brain electrical stimulation (DBES) of the brainstem reticular formation is a less common technique used to prevent sleep, and while this methodology may also carry unwanted effects, it avoids stressful conditions. In the present study, we examined the relationship between sleep and nursing, and how different sleep deprivation methodologies impact nursing and lactation. For this purpose, we carried out two sets of experiments. First, we correlated sleep and waking states with different nursing parameters of lactating rats under undisturbed conditions. Second, we slept deprived another group of mother rats using two different techniques: GH and DBES. Our main findings show that sleeping time was positively correlated with the time devote to nurse the pups, but not either with milk ejection or pup weight gain. When mother rats were sleep deprived, maternal behavior was fragmented using both methods, but was substantially more disrupted when using GH. Additionally, lactating dams were capable of ejecting milk and their pups gained weight despite of being sleep deprived using both techniques, but these parameters were significantly reduced using GH compared to control values, while DBES did not differ from control group. Overall, these results suggest that sleep and nursing are behaviorally compatible, but in disagreement with previous findings, we concluded that sleep is not necessary for milk ejection. These observations have critical implications for using the rat as a model to explore sleep loss during the postpartum period.

Differential Effect of Dopamine D4 Receptor Activation on Low-Frequency Oscillations in the Prefrontal Cortex and Hippocampus May Bias the Bidirectional Prefrontal-Hippocampal Coupling.

Dopamine D4 receptor (D4R) mechanisms are implicated in psychiatric diseases characterized by cognitive deficits, including schizophrenia, ADHD, and autism. The cellular mechanisms are poorly understood, but impaired neuronal synchronization in cortical networks was proposed to contribute to these deficits. In animal experiments, D4R activation was shown to generate aberrant increased gamma oscillations and to reduce performance on cognitive tasks requiring functional prefrontal cortex (PFC) and hippocampus (HPC) networks. While fast oscillations in the gamma range are important for local synchronization within neuronal ensembles, long-range synchronization between distant structures is achieved by slow rhythms in the delta, theta, alpha ranges. The characteristics of slow oscillations vary between structures during cognitive tasks. HPC activity is dominated by theta rhythm, whereas PFC generates unique oscillations in the 2–4 Hz range. In order to investigate the role of D4R on slow rhythms, cortical activity was recorded in rats under urethane anesthesia in which slow oscillations can be elicited in a controlled manner without behavioral confounds, by electrical stimulation of the brainstem reticular formation. The local field potential segments during stimulations were extracted and subjected to fast Fourier transform to obtain power density spectra. The selective D4R agonist A-412997 (5 and 10 mg/kg) and antagonists L-745870 (5 and 10 mg/kg) were injected systemically and the peak power in the two frequency ranges were compared before and after the injection. We found that D4R compounds significantly changed the activity of both HPC and PFC, but the direction of the effect was opposite in the two structures. D4R agonist enhanced PFC slow rhythm (delta, 2–4 Hz) and suppressed HPC theta, whereas the antagonist had an opposite effect. Analogous changes of the two slow rhythms were also found in the thalamic nucleus reuniens, which has connections to both forebrain structures. Slow oscillations play a key role in interregional cortical coupling; delta and theta oscillations were shown in particular, to entrain neuronal firing and to modulate gamma activity in interconnected forebrain structures with a relative HPC theta dominance over PFC. Thus, the results of this study indicate that D4R activation may introduce an abnormal bias in the bidirectional PFC–HPC coupling which can be reversed by D4R antagonists.

Responses evoked by electrical stimulation of the brainstem reticular formation in the jaw-opening and hypoglossal motor nerves of an arterially perfused rat preparation

The interneuronal system in the brainstem reticular formation plays an important role in elaborate muscle coordination during various orofacial motor behaviors. In this study, we examined the distribution in the brainstem reticular formation of the sites that induce monosynaptic motor activity in the mylohyoid (jaw-opening) and hypoglossal nerves using an arterially perfused rat preparation. Electrical stimulation applied to 286 and 247 of the 309 sites in the brainstem evoked neural activity in the mylohyoid and hypoglossal nerves, respectively. The mean latency of the first component in the mylohyoid nerve response was significantly shorter than that in the hypoglossal nerve response. Moreover, the latency histogram of the first component in the hypoglossal nerve responses was bimodal, which was separated by 4.0 ms. The sites that induced short-latency (<4.0 ms) motor activity in the mylohyoid nerve and the hypoglossal nerve were frequently distributed in the rostral portion and the caudal portion of the brainstem reticular formation, respectively. Such difference in distributions of short-latency sites for mylohyoid and hypoglossal nerve responses likely corresponds to the distribution of excitatory premotor neurons targeting mylohyoid and hypoglossal motoneurons.

The Ascending Reticular Activating System.

Discovery of the ascending reticular activating system (ARAS) can be attributed to work done in research neuroscientist Horace Magoun's laboratory. Before this finding, most scientists would focus on the diencephalon (and anterior midbrain) but not more caudally. Stimulation of the medial bulbar reticular formation in the pontine and midbrain tegmentum resulted disappearance of synchronized discharge and low-voltage fast activity. The effects were mediated by a thalamic projection system. This finding was a dramatic departure from the early philosophers' ascription of the awake soul to the ventricles (Galen), lumbosacral cord (Plato), pineal gland (Descartes), and even from more modern nineteenth- and twentieth-century hypotheses that the corpus striatum or periaqueductal gray matter housed the "seat of awareness." Magoun and his collaborators closed in on its true location in the cephalic brainstem-clinicians and neuropathologists would soon follow.

An evaluation of the effect of pulse-shape on grey and white matter stimulation in the rat brain

Despite the current success of neuromodulation, standard biphasic, rectangular pulse shapes may not be optimal to achieve symptom alleviation. Here, we compared stimulation efficiency (in terms of charge) between complex and standard pulses in two areas of the rat brain. In motor cortex, Gaussian and interphase gap stimulation (IPG) increased stimulation efficiency in terms of charge per phase compared with a standard pulse. Moreover, IPG stimulation of the deep mesencephalic reticular formation in freely moving rats was more efficient compared to a standard pulse. We therefore conclude that complex pulses are superior to standard stimulation, as less charge is required to achieve the same behavioral effects in a motor paradigm. These results have important implications for the understanding of electrical stimulation of the nervous system and open new perspectives for the design of the next generation of safe and efficient neural implants.

Prefrontal-hippocampal coupling by theta rhythm and by 2-5Hz oscillation in the delta band: The role of the nucleus reuniens of the thalamus.

Rhythmic synchronizations of hippocampus (HC) and prefrontal cortex (PFC) at theta frequencies (4-8Hz) are thought to mediate key cognitive functions, and disruptions of HC-PFC coupling were implicated in psychiatric diseases. Theta coupling is thought to represent a HC-to-PFC drive transmitted via the well-described unidirectional HC projection to PFC. In comparison, communication in the PFC-to-HC direction is less understood, partly because no known direct anatomical connection exists. Two recent findings, i.e., reciprocal projections between the thalamic nucleus reuniens (nRE) with both PFC and HC and a unique 2-5Hz rhythm reported in the PFC, indicate, however, that a second low-frequency oscillation may provide a synchronizing signal from PFC to HC via nRE. Thus, in this study, we recorded local field potentials in the PFC, HC, and nRE to investigate the role of nRE in PFC-HC coupling established by the two low-frequency oscillations. Using urethane-anesthetized rats and stimulation of pontine reticular formation to experimentally control the parameters of both forebrain rhythms, we found that theta and 2-5Hz rhythm were dominant in HC and PFC, respectively, but were present and correlated in all three signals. Removal of nRE influence, either statistically (by partialization of PFC-HC correlation when controlling for the nRE signal) or pharmacologically (by lidocaine microinjection in nRE), resulted in decreased coherence between the PFC and HC 2-5-Hz oscillations, but had minimal effect on theta coupling. This study proposes a novel thalamo-cortical network by which PFC-to-HC coupling occurs via a 2-5Hz oscillation and is mediated through the nRe.

Differential effects of systemic morphine on responses elicited by tooth pulp stimulation of nociceptive neurons in lateral and medial thalamic nuclei.

The effects of intravenous morphine on responses of feline thalamic nociceptive neurons receiving afferent input from the tooth pulp (TP) were investigated. Morphine suppressed responses to TP stimulation in both tooth pulp specific (TPS) and wide dynamic range (WDR) neurons with TP input recorded from the nucleus ventralis posteromedialis (VPM). However, there was scant morphine effect on responses to stimulation of trigeminothalamic tract (TTT) fibers in the trigeminal medial lemniscus. Furthermore, in nociceptive neurons with TP input recorded from nucleus centralis lateralis (CL) and parafascicularis (Pf) of the intralaminar nuclei, intravenous morphine suppressed responses both to stimulation of the mesencephalic reticular formation (MRF) as well as TP stimulation. The suppressive action of morphine on responses elicited by TP stimulation of VPM, CL and Pf neurons was antagonized by intravenous naloxone (1 mg/kg). Results suggest that intravenous morphine suppresses synaptic transmission of nociceptive impulses in the intralaminar nuclei as well as in the lower brain stem but not in the VPM.

Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat.

Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input, and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation, and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability, and affordability. Our open-source closed-loop DBS system is effective, and warrants further research using open-source hardware for closed-loop neuromodulation.

Overactive Bladder and Pontine Reticular Formation

Background: The etiology of overactive bladder (OAB) remains unclear. Observed neurogenic factors in the literature are limited to suprapontine or spinal pathologies. The blink reflex is a useful tool in the evaluation of brainstem functions. Blink reflex latency times were evaluated in order to reveal pathology in the brainstem. Methods: A total of 60 women, 30 patients with idiopathic OAB and 30 healthy controls, were enrolled in the study. Blink reflex latency times were analyzed by electrical stimulation of the supraorbital nerve. Two responses in the orbicularis oculi muscle, early ipsilateral response (R1) and late bilateral response (R2) latency times, were recorded. Results: Mean ages of the patients and controls were 51.9 ± 5.3 and 49.2 ± 6.2 years, respectively. R2 latency times were significantly higher in patients than in controls. However, R1 latency times were similar between the two groups. Conclusions: The results of the study suggest a significant relation between late blink latency times and OAB. An oligosynaptic path via the trigeminal nuclei is responsible for R1; however, R2 response is relayed through the reticular formation. Stimulation of pontine reticular formation inhibits micturition contraction. In some patients, idiopathic OAB may result from reticular formation-originated pathology. Additional studies on other reticular formation-mediated reflexes are needed to reveal possible dysfunction of reticular formation.

Is There a Relation between Reticular Formation and Storage Symptoms in Men.

To reveal brainstem originated pathology in men with different types of lower urinary tract symptoms blink reflex latency times were assessed. A total of 32 men, 16 with storage and 16 with voiding symptoms, were enrolled in the study. Blink reflex latency times were analyzed through electrical stimulation of the supraorbital nerve. Two responses in the orbicularis oculi muscle were recorded: the latency times for the early ipsilateral response, R1, and the late bilateral responses, R2. The mean ages of the patients with storage and voiding symptoms were 57.31 ± 6.87 and 58.06 ± 6.29 years, respectively. The R2 latency times were significantly longer in men with storage symptoms. However, the R1 latency times were similar for the two groups. Late blink latency times were long only in patients who had storage symptoms. An oligosynaptic path through the trigeminal nuclei, which includes one or two interneurons, is responsible for early response; however, late response is relayed through a polysynaptic path, including neurons in the reticular formation. It has also been shown that stimulation of the pontine reticular formation inhibits the micturition contraction. In some patients, storage symptoms may result from pathology that originates with the reticular formation and this pathology may lead to increases in late blink latency times. Additional studies are needed on other reflexes that are mediated through reticular formation, in order to show the possible dysfunction of the reticular formation in men with storage symptoms.

Activation of 5-HT6 Receptors Modulates Sleep–Wake Activity and Hippocampal Theta Oscillation

The modulatory role of 5-HT neurons and a number of different 5-HT receptor subtypes has been well documented in the regulation of sleep-wake cycles and hippocampal activity. A high level of 5-HT(6) receptor expression is present in the rat hippocampus. Further, hippocampal function has been shown to be modulated by both 5-HT(6) agonists and antagonists. In the current study, the potential involvement of 5-HT(6) receptors in the control of hippocampal theta rhythms and sleep-wake cycles has been investigated. Hippocampal activity was recorded by intracranial hippocampal electrodes both in anesthetized (n = 22) and in freely moving rats (n = 9). Theta rhythm was monitored in different sleep-wake states in freely moving rats and was elicited by stimulation of the brainstem reticular formation under anesthesia. Changes in theta frequency and power were analyzed before and after injection of the 5-HT(6) antagonist (SAM-531) and the 5-HT(6) agonist (EMD386088). In freely moving rats, EMD386088 suppressed sleep for several hours and significantly decreased theta peak frequency, while, in anesthetized rats, EMD386088 had no effect on theta power but significantly decreased theta frequency, which could be blocked by coadministration of SAM-531. SAM-531 alone did not change sleep-wake patterns and had no effect on theta parameters in both unanesthetized and anesthetized rats. Decreases in theta frequency induced by the 5-HT(6) receptor agonist correspond to previously described electrophysiological patterns shared by all anxiolytic drugs, and it is in line with its behavioral anxiolytic profile. The 5-HT(6) antagonist, however, failed to potentiate theta power, which is characteristic of many pro-cognitive substances, indicating that 5-HT(6) receptors might not tonically modulate hippocampal oscillations and sleep-wake patterns.

Movement- and behavioral state-dependent activity of pontine reticulospinal neurons

Forty-five years ago Shik and colleagues were the first to demonstrate that electrical stimulation of the dorsal pontine reticular formation induced fictive locomotion in decerebrate cats. This supraspinal motor site was subsequently termed the “mesencephalic locomotor region (MLR)”. Cholinergic neurons of the pedunculopontine tegmental nucleus (PPT) have been suggested to form, or at least comprise in part, the neuroanatomical basis for the MLR, but direct evidence is lacking. In an effort to clarify the location and activity profiles of pontine reticulospinal neurons supporting locomotor behaviors, we employed in the present study a retrograde tracing method in combination with single-unit recordings and antidromic spinal cord stimulation as well as characterized the locomotor- and behavioral state-dependent activities of both reticulospinal and non-reticulospinal neurons. The retrograde labeling and antidromic stimulation responses suggested a candidate group of reticulospinal neurons that were non-cholinergic and located just medial to the PPT cholinergic neurons and ventral to the cuneiform nucleus (CnF). Unit recordings from these reticulospinal neurons in freely behaving animals revealed that the preponderance of neurons fired in relation to motor behaviors and that some of these neurons were also active during rapid eye movement sleep. By contrast, non-reticulospinal neurons, which likely included cholinergic neurons, did not exhibit firing activity in relation to motor behaviors. In summary, the present study provides neuroanatomical and electrophysiological evidence that non-cholinergic, pontine reticulospinal neurons may constitute the major component of the long-sought neuroanatomic MLR in mammals.

Stabilization of visual responses through cholinergic activation

Neuronal processing of sensory information requires that rapidly changing synaptic inputs are continuously transformed into action potentials. Variability of spike firing is generally considered as noise and might therefore interfere with the reliability of synaptic transmission in sensory systems. In a system in which the number of spikes is a variable that determines the quality of neuronal transmission, variability of spike counts is a paradoxical attribute. In contrast, in a system in which precisely correlated spike firing can influence synaptic integration, response variability might be used as an additional mechanism for coding information. As acetylcholine has been shown to reduce spike-frequency adaptation and enhance gamma frequency (21–70 Hz) oscillations, we set out to study the influence of cholinergic modulation on the variability of spike counts and gamma oscillations. Iontophoretic application of carbachol, a cholinergic agonist, in cat primary visual cortex or electrical stimulation of the mesencephalic reticular formation reduced the spike count variability and stabilized gamma frequency oscillations of visually induced responses. Response stabilization was correlated with enhancement of gamma-frequency oscillations but not with averaged firing rates. Lowering variability of sensory responses might be a mechanism to stabilize and improve reliability of neuronal transmission. Cholinergic activation may therefore influence the efficacy of neuronal transmission by modulating the precise timing of neuronal responses.

Response to Kanno et al. “Dorsal Column Stimulation in Persistent Vegetative State”

Accurate citation of references is one of the fundamentals of scientific journals. In the introduction of their manuscript, the authors described the treatment of vegetative state, and there is a very serious mistake in their citation. They stated that “Deep brain stimulation has been used by Cohadon and Richer in 1993, and more recently, by Yamamoto and Katayama. Both studies found improvement in such patients with PVS after stimulation of CM-Pf or mesencephalic reticular formation.”

Differential origin of reticulospinal drive to motoneurons innervating trunk and hindlimb muscles in the mouse revealed by optical recording

To better understand how the brainstem reticular formation controls and coordinates trunk and hindlimb muscle activity, we used optical recording to characterize the functional connections between medullary reticulospinal neurons and lumbar motoneurons of the L2 segment in the neonatal mouse. In an isolated brainstem-spinal cord preparation, synaptically induced calcium transients were visualized in individual MNs of the ipsilateral and contralateral medial and lateral motor columns (MMC, LMC) following focal electrical stimulation of the medullary reticular formation (MRF). Stimulation of the MRF elicited differential responses in MMC and LMC, according to a specific spatial organization. Stimulation of the medial MRF elicited responses predominantly in the LMC whereas stimulation of the lateral MRF elicited responses predominantly in the MMC. This reciprocal response pattern was observed on both the ipsilateral and contralateral sides of the spinal cord. To ascertain whether the regions stimulated contained reticulospinal neurons, we retrogradely labelled MRF neurons with axons coursing in different spinal funiculi, and compared the distributions of the labelled neurons to the stimulation sites. We found a large number of retrogradely labelled neurons within regions of the gigantocellularis reticular nucleus (including its pars ventralis and alpha) where most stimulation sites were located. The existence of a mediolateral organization within the MRF, whereby distinct populations of reticulospinal neurons predominantly influence medial or lateral motoneurons, provides an anatomical substrate for the differential control of trunk and hindlimb muscles. Such an organization introduces flexibility in the initiation and coordination of activity in the two sets of muscles that would satisfy many of the functional requirements that arise during postural and non-postural motor control in mammals.

Coordination of eye and head components of movements evoked by stimulation of the paramedian pontine reticular formation

Constant frequency microstimulation of the paramedian pontine reticular formation (PPRF) in head-restrained monkeys evokes a constant velocity eye movement. Since the PPRF receives significant projections from structures that control coordinated eye-head movements, we asked whether stimulation of the pontine reticular formation in the head-unrestrained animal generates a combined eye-head movement or only an eye movement. Microstimulation of most sites yielded a constant-velocity gaze shift executed as a coordinated eye-head movement, although eye-only movements were evoked from some sites. The eye and head contributions to the stimulation-evoked movements varied across stimulation sites and were drastically different from the lawful relationship observed for visually-guided gaze shifts. These results indicate that the microstimulation activated elements that issued movement commands to the extraocular and, for most sites, neck motoneurons. In addition, the stimulation-evoked changes in gaze were similar in the head-restrained and head-unrestrained conditions despite the assortment of eye and head contributions, suggesting that the vestibulo-ocular reflex (VOR) gain must be near unity during the coordinated eye-head movements evoked by stimulation of the PPRF. These findings contrast the attenuation of VOR gain associated with visually-guided gaze shifts and suggest that the vestibulo-ocular pathway processes volitional and PPRF stimulation-evoked gaze shifts differently.

Arousal of cerebral cortex electroencephalogram consequent to high-frequency stimulation of ventral medullary reticular formation

We have theorized that large neurons in the ventral and medial reticular formation of the medulla are critical for both autonomic and cortical arousal. To test this theory, we anesthetized rats with urethane, lowered concentric bipolar stimulating electrodes into the medullary reticular formation, and implanted electroencephalogram (EEG) and ECG recording electrodes. We stimulated in the medulla with pulse frequencies ranging from 50 to 300 Hz while recording cortical EEG and ECG. These female rats were ovariectomized, and one subgroup was administered estradiol. Electrical stimulation at either 200 or 300 Hz among the large medullary reticular neurons in nucleus paragigantocellularis (PGi) caused a significant reduction in the portion of the EEG power spectrum represented by delta-waves (0.1-4 Hz) and -waves (4.1-8 Hz). Correspondingly, there were increases in gamma-wave power (22-50 Hz), especially when using 300 Hz. Stimulation at </=100 Hz produced fewer changes in cortical EEG. The major features of these results were not significantly different according to estradiol treatment. In contrast, estradiol administration significantly lowered ECG. Electrical stimulation in PGi increased ECG in vehicle control animals, but decreased it in estradiol-treated animals. Regarding the EEG, we conclude that, even in anesthetized animals, stimulation of PGi reticular neurons can increase cortical arousal and that high frequencies of stimulation amplify this effect.

The effect of atropine administered in the medial septum or hippocampus on high‐ and low‐frequency theta rhythms in the hippocampus of urethane anesthetized rats

Cholinergic mechanisms are critical for the generation of hippocampal theta rhythm. Cholinergic innervation of the hippocampus originates from the medial septum (MS) and cholinergic receptors are expressed in both the MS and hippocampus. In this study, we compared the effects of the muscarinic receptor antagonist atropine in the MS and the hippocampus on theta generation. Hippocampal theta rhythm was elicited by electrical stimulation of the pontine reticular formation using series of stimuli with varying intensities. Atropine was administered either systemically (50 mg/kg i.p.) or locally in the MS (microdialysis; 25 and 75 mM for 30 or 90 min) or in the hippocampus on one side (microinjection; 20 or 40 ug). The relative power at the peak theta frequency was calculated and averaged over episodes of low-intensity and high-intensity stimulations. We found that atropine drastically reduced theta rhythmic synchronization when injected in either location. After MS administration of atropine, however, high-frequency theta elicited by high-intensity stimuli was more resistant (58% and 67% decrease after 25 mM and 75 mM atropine, respectively) than slow theta elicited by low-intensity stimuli (86% and 91% decrease). There was no significant difference between the powers of the two oscillations after hippocampal injections (70-75% decrease). We conclude that the theta suppressing effect of atropine involves both hippocampal and septal mechanisms and that low-frequency theta as compared with fast theta rhythm is more sensitive to muscarinic acetylcholine receptor antagonism in the MS but not in the hippocampus.

Propofol, more than halothane, depresses electroencephalographic activation resulting from electrical stimulation in reticular formation

Halothane and propofol depress the central nervous system, and this is partly manifested by a decrease in electroencephalographic (EEG) activity. Little work has been performed to determine the differences between these anesthetics with regard to their effects on evoked EEG activity. We examined the effects of halothane and propofol on EEG responses to electrical stimulation of the reticular formation. Rats (n= 12) were anesthetized with either halothane or propofol, and EEG responses were recorded before and after electrical stimulation of the reticular formation. Two anesthetic concentrations were used (0.8 and 1.2 times the amount needed to prevent gross, purposeful movement in response to supramaximal noxious stimulation), and both anesthetics were studied in each rat using a cross-over design. Electrical stimulation in the reticular formation increased the spectral edge (SEF) and median edge (MEF) frequencies by approximately 1-2 Hz during halothane anesthesia at low and high concentrations. During propofol anesthesia, MEF increased at the low propofol infusion rate, but SEF was unaffected. At the high propofol infusion rate, SEF and MEF decreased following electrical stimulation in the reticular formation. At immobilizing concentrations, propofol produces a larger decrease than halothane in EEG responses to reticular formation stimulation, consistent with propofol having a more profound depressant effect on cortical and subcortical structures.

Patterns of primary afferent depolarization of segmental and ascending intraspinal collaterals of single joint afferents in the cat

We have examined in the anesthetized cat the threshold changes produced by sensory and supraspinal stimuli on intraspinal collaterals of single afferents from the posterior articular nerve (PAN). Forty-eight fibers were tested in the L3 segment, in or close to Clarke's column, and 70 fibers in the L6-L7 segments within the intermediate zone. Of these, 15 pairs of L3 and L6-L7 collaterals were from the same afferent. Antidromically activated fibers had conduction velocities between 23 and 74 m/s and peripheral thresholds between 1.1 and 4.7 times the threshold of the most excitable fibers (xT), most of them below 3 xT. PAN afferents were strongly depolarized by stimulation of muscle afferents and by cutaneous afferents, as well as by stimulation of the bulbar reticular formation and the midline raphe nuclei. Stimulation of muscle nerves (posterior biceps and semitendinosus, quadriceps) produced a larger PAD (primary afferent depolarization) in the L6-L7 than in the L3 terminations. Group II were more effective than group I muscle afferents. As with group I muscle afferents, the PAD elicited in PAN afferents by stimulation of muscle nerves could be inhibited by conditioning stimulation of cutaneous afferents. Stimulation of the cutaneous sural and superficial peroneal nerves increased the threshold of few terminations (i.e., produced primary afferent hyperpolarization, PAH) and reduced the threshold of many others, particularly of those tested in the L6-L7 segments. Yet, there was a substantial number of terminals where these conditioning stimuli had minor or no effects. Autogenetic stimulation of the PAN with trains of pulses increased the intraspinal threshold in 46% and reduced the threshold in 26% of fibers tested in the L6-L7 segments (no tests were made with trains of pulses on fibers ending in L3). These observations indicate that PAN afferents have a rather small autogenetic PAD, particularly if this is compared with the effects of heterogenetic stimulation. Therefore, the depression of the PAN intraspinal fields produced by autogenetic stimulation described by Rudomin et al. (Exp Brain Res DOI 10.1007/s00221-006-0600-x, 2006) may be ascribed to other mechanisms besides a GABAa PAD. It is suggested that the small or no autogenetic PAD displayed by the examined joint afferents prevents presynaptic filtering of their synaptic actions and preserves the original information generated in the periphery. This could be important for proper adjustment of limb position.