Biomedical subjects

E Garcia-Rill

Publications and source records attributed to E Garcia-Rill.

At least 55 records · Page 3Linked to original sources

PubMed1995

A middle-latency auditory-evoked potential in the rat.

Previous studies have established the presence of a middle-latency auditory-evoked potential that is characterized by a) sleep-state dependence, b) low following frequency (i.e., rapid habituation to repetitive stimulation), and c) blockade by the cholinergic antagonist, scopolamine. A vertex-recorded evoked potential having these characteristics was described in humans at a 50-80 ms latency (termed the P1 or.P50 potential) and in the cat at a 20-25 ms latency (termed wave A). These studies were undertaken to determine if a click stimulus-evoked potential having the same characteristics was present in the intact rat. Vertex and auditory cortex recordings in intact rats studied in a sound-attenuating chamber and exposed to free-field click stimuli showed a) the presence of a vertex recorded potential at a 11-15 ms latency, termed P13, and of an auditory cortex recorded potential at a 7-11 ms latency, termed Pa; b) the P13 was present during waking and paradoxical sleep but absent in slow-wave sleep, while Pa was present in all sleep-wake states; c) the P13 habituated markedly at stimulation rates above 1 Hz while Pa did not; and d) the P13 was blocked by low doses of scopolamine while Pa was not. These studies demonstrate the presence of a P1-like potential in the rat at a 13 +/- 2 ms latency.

Acoustic Stimulation↗

PubMed1994

Electrical activation and inhibition of respiration in vitro.

The present studies employed the neonatal rat rib-attached brain stem-spinal cord preparation to examine the effects of electrical stimulation of the medulla and the pons on respiratory-like activity. The investigation focused on determining whether electrical stimulation of the medulla can be used to modulate respiratory-like activity, whether electrical stimulation of the pons can inhibit respiratory-like activity, and how the preparation responds when both the medulla and the pons are stimulated simultaneously. The results suggest that: (1) stimulation of the ventromedial part of the medulla entrains the onset and the frequency of respiratory-like electromyographic (EMG) bursting most effectively and drives the respiratory rate as high as 0.4 Hz; (2) both ventromedial and ventrolateral pontine stimulation inhibited respiratory-like EMG bursting, but only ventrolateral pontine stimulation was followed by post-stimulation inhibition; (3) when the medulla and the pons were stimulated simultaneously, pontine stimulation-induced inhibition outweighed medullary stimulation-induced activation and resulted in a temporary cessation of respiratory-like EMG bursting.

Animals↗

PubMed1994

The P1: insights into attention and arousal.

The authors provide evidence that four mesencephalic nuclei, two of which are cholinergic and two of which are catecholaminergic, serve as oscillators capable of modulating a number of interrelated rhythmic functions. These include sleep-wake cycles, locomotion, blood pressure, respiratory rate, heart rate, mastication, micturition, and saccadic eye movements. The P1 auditory evoked potential is generated by ascending cholinergic projections from one of these nuclei, the pedunculopontine nucleus, and thus serves as a clinical tool to monitor the integrity of this system.

Adult↗

PubMed1992

Spinal cord stimulation-induced locomotion in the adult cat.

Epidural and subdural stimulation of the dorsal surface of the spinal cord was found to elicit locomotion in the decerebrate cat in the active and fictive locomotion preparations. Stimulation of the cervical enlargement induced stepping in all four limbs, while stimulation of the lumbosacral enlargement induced hindlimb stepping. Lumbosacral enlargement stimulation induced hindlimb locomotion starting four hours following an acute midthoracic spinal cord transection. The preservation of the overall locomotor pattern and relationships between muscle groups, and of coordination between hindlimbs following transection, suggests that lumbar enlargement stimulation may be activating an intrinsically organized system. These findings suggest a method which may be applied clinically for the induction of limb alternation following epidural stimulation of the spinal cord.

Animals↗

PubMed1992

Respiration in vitro: I. Spontaneous activity.

The present report describes respiratory-like activity recorded from intercostal muscles in the neonatal rat in vitro brain stem-spinal cord, rib-attached preparation. In this preparation from 1- to 4-day-old rats, spontaneous rhythmic and synchronized upward movements of the rib cage coincided with the recorded muscle activity. Spontaneous respiratory-like activity showed a frequency in the range of 0.05-0.2 Hz, with single-, double-, and mixed-burst patterns. Spontaneous activity declined over time, but increased in frequency as temperature increased. Multilevel recordings showed a cephalocaudal order of bursting of intercostal muscles. Brain stem transections at the prepontine level did not affect spontaneous frequency, whereas premedullary transections resulted in an increase in spontaneous respiratory frequency. High spinal transections eliminated spontaneous respiratory-like activity. These results suggest that there is a well-organized pontomedullary pattern generator for respiratory-like activity in this preparation, which can be modulated by temperature. The characteristics of these electromyographic (EMG) recordings allow comparison with previous in vitro studies of respiratory-like activity using nerve activity and in vivo studies using EMG activity. These results provide basic information on the spontaneous activity of this preparation as a prelude to the study of the effects of electrical stimulation of the spinal cord to induce respiratory-like activity, as described in the companion article.

Animals↗

PubMed1992

Respiration in vitro: II. Electrical stimulation.

The present report describes electrical-stimulation-induced activity recorded from intercostal muscles in the neonatal rat rib-attached, in vitro brain stem-spinal cord preparation. The muscle bursts induced by electrical stimulation included a short-latency twitch contraction and a long-latency modulated contraction similar to that observed during spontaneous respiratory-like activity. Multilevel recordings showed a cephalocaudal order of recruitment of intercostal muscles similar to that observed during spontaneous activity. The optimal parameters of stimulation were 2-msec pulses delivered at 0.1-0.2 Hz. Trains of pulses also were effective. These movements could be induced following stimulation of various sites within each segment of the spinal cord, with the lowest threshold sites located in the ventrolateral funiculus and intermediate gray. Stimulation of every cervical segment was effective in inducing respiratory-like activity, with the lowest-threshold segments being C1, C2, and C5. These results suggest that low-frequency, long-duration pulses applied directly to the spinal cord can induce respiratory-like activity similar to that observed during spontaneous activity in the neonatal rat, rib-attached in vitro brain stem-spinal cord preparation. The ability to elicit a coordinated respiratory pattern even after a high spinal transection suggests that such stimulation may be effective in inducing respiratory-like activity in the absence of descending brain stem connections.

Animals↗

PubMed1991

Stimulation-induced setting of postural muscle tone in the decerebrate rat.

These studies demonstrate the presence of pontomedullary areas in the rat brainstem which, when stimulated electrically, serve to set postural muscle tone in the hindlimbs. Low amplitude stimulation of the dorsal tegmental field (DTF) was found to inhibit postural muscle tone and, in some rats, was found to decrease mean arterial pressure. Low amplitude stimulation of the ventral tegmental field (VTF) was found to increase postural muscle tone and, in all cases tested, was found to increase mean arterial pressure.

Animals↗

PubMed1991

Fibroblast growth factor-induced increased survival of cholinergic mesopontine neurons in culture.

Basic fibroblast growth factor (bFGF) was found to increase the survival of immunocytochemically-identified cholinergic mesopontine neurons in dissociated cell cultures of embryonic rat midbrain. In contrast, cultures exposed to, (a) bFGF and an antibody to bFGF, (b) antibody to bFGF alone, or (c) untreated, contained approximately half the number of cholinergic neurons compared to bFGF-treated cultures.

Animals↗

PubMed1991

L-dopa-induced air-stepping in decerebrate developing rats.

Developing rats were anesthetized and a precollicular brainstem transection performed. Administration of L-3,4-dihydroxyphenylalanine (L-DOPA, 100 mg/kg, s.c.) induced locomotion in groups of animals 0-3, 6-8, 14-16 and 20-22 days of age. At early stages in development (0-3 days), continuous, long-lasting air-stepping was induced consisting of 4-limb walking with stronger alternation in the forelimbs compared to the hindlimbs. At 6-8 days of age, continuous air-stepping was characterized by better agreement between forelimb and hindlimb step cycles. By 14-16 days of age, the hindlimbs showed stronger and faster stepping than the forelimbs. The first evidence of consistent galloping was observed in this age group. In some cases, the forelimbs were held extended and only the hindlimbs walked or galloped. At 20-22 days, walking and galloping became episodic and the hindlimbs typically galloped while the forelimbs alternated. Each age group was tested for overground locomotion. Only in the 20-22 day group was weight-bearing overground stepping observed. At earlier ages, limb alternation was evident but of insufficient strength to lift the body off the ground. In general, the duration of the effect of the same dose of L-DOPA decreased with age. Animals in each group which received a mid-thoracic spinal cord transection showed forelimb alternation but not hindlimb stepping. These results indicate that L-DOPA induces stepping by activating brainstem and/or spinal centers via an as yet unknown mechanism. The pattern of the development of gait (forelimb to hindlimb gradient) at various ages was similar to that observed in intact developing rats.

Aging↗

PubMed1991

The pedunculopontine nucleus.

In an effort to account for a large number of reported functions mediated by a small portion of the midbrain, a hypothesis is advanced as a basis for discussion and not as established fact and is guided by reports from a large number of laboratories working on the same region but using widely disparate preparations. Overall, the hypothesized model suggests an underlying mechanism of action for what is essentially the ascending reticular activating system. The model proposed will hopefully be tested stringently in order to arrive at a better understanding of brain stem mechanisms modulating a host of rhythmic functions.

Humans↗

PubMed1991

The brain stem reticular formation in schizophrenia.

Post-mortem brain tissue was obtained from four patients with schizophrenia and five controls to study cell groups in the brain stem reticular formation. Cholinergic neurons in the pedunculopontine nucleus (PPN) and lateral dorsal tegmental nucleus (LDT) were labeled using nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase histochemistry, while catecholaminergic neurons of the locus ceruleus (LC) were labeled immunocytochemically using an antibody to tyrosine hydroxylase. In schizophrenic patients, there were increased numbers of neurons in the PPN labeled by NADPH-diaphorase and reduced cell size in the LC. These results implicate the reticular formation as a possible pathophysiological site for at least some patients with schizophrenia. This also suggests that some of the deficits observed may be based on faulty neurodevelopment.

Aged↗

PubMed1991

Control of locomotion in vitro: I. Deafferentation.

We previously described the ability to induce adult-like, coordinated airstepping following electrical stimulation of the brainstem in the hindlimb-attached, in vitro brainstem-spinal cord preparation. These findings suggest the presence at birth of supraspinal systems capable of activating and modulating spinal locomotor mechanisms, which presumably also are present at birth. The current study employed the hindlimb-attached in vitro brainstem-spinal cord preparation from 0- to 4-day-old rats maintained in oxygenated artificial cerebrospinal fluid. After the control threshold-frequency relationship for eliciting airstepping was established, the dorsal roots to the attached limbs were severed and the procedure was repeated. No changes in electrical threshold or major differences in the elicited locomotor pattern were observed after deafferentation, although the amplitude of the electromyograms decreased. The mean frequency of alternation at threshold before deafferentation was similar to that after deafferentation. However, the maximum mean frequency induced by suprathreshold stimulation was significantly higher after deafferentation than that before deafferentation. These results suggest that (1) the supraspinal modulation of spinal locomotor mechanisms is not entirely dependent on afferent input; (2) intrinsic spinal locomotor mechanisms are present in the spinal cord at birth; and (3) afferent input may limit the maximum frequency of alternation of the limbs early in development.

Afferent Pathways↗

PubMed1991

Control of locomotion in vitro: II. Chemical stimulation.

Previous studies have described the presence of alternating activity induced in left and right ventral roots of the neonate rat in vitro brainstem-spinal cord preparation, following application of certain neuroactive substances to the bathing solution. The present findings show the presence of chemically induced, adult-like coordinated airstepping demonstrated by electromyographic recordings in the hindlimb-attached in vitro brainstem-spinal cord preparation. Analysis of muscular activity demonstrated alternation between antagonists of one limb and between agonists of different limbs, as well as a proximodistal delay in agonists active at different joints of the same limb. Neuroactive agents were applied independently to either the brainstem or spinal cord bath. The substances surveyed in the present studies included some of those used previously, as well as additional compounds: bicuculline and picrotoxin (gamma-aminobutyric acid-ergic antagonists), N-methyl-D-aspartic acid (excitatory amino acid agonist), substance P, acetylcholine, carbachol (cholinergic agonist), and serotonin. Application of these substances to the brainstem bath produced rhythmic airstepping. Application of dopamine, aspartate, glutamate, and N-methyl-D-aspartic acid to the spinal cord bath also produced rhythmic airstepping, while application of acetylcholine produced tonic, long-lasting co-contractions. These findings reveal the presence of several neurochemical systems in the central nervous system that can be activated at birth to induce coordinated airstepping in the neonate rat in vitro brainstem-spinal cord preparation.

Acetylcholine↗

PubMed1991

Locomotion induced by spinal cord stimulation in the neonate rat in vitro.

The present studies employed the neonate rat brain stem-spinal cord preparation to determine whether electrical stimulation of the lumbosacral enlargement (LE) of the spinal cord itself can be used to elicit locomotion, and whether or not such stimulation persists in inducing locomotion following midthoracic spinal cord transection or hindlimb deafferentation. Results suggest that (1) stimulation of the dorsal columns or ventral funiculus of the LE is effective in inducing airstepping in the neonatal rat brain stem-spinal cord limb-attached preparation; (2) central disconnection by midthoracic spinal cord transection does not alter LE-stimulation-induced airstepping and may lead to an increase in stepping frequency if suprathreshold stimulation is used; and (3) dorsal root section also leads to an increase in the frequency of suprathreshold LE-stimulation-induced locomotion, but there is not further increase in frequency if a spinal cord transection is performed in addition to dorsal rhizotomy.

Afferent Pathways↗

PubMed1990

Posterior midbrain-induced locomotion.

The purpose of this study was to determine the nature of the neurochemical signals which impinge on the mesencephalic locomotor region (MLR) to produce locomotion in the rat. Injections of GABA antagonists into NADPH diaphorase-positive regions (PPN) were found to induce locomotion for short episodes (5-30 sec) which were repeated for several minutes (1-40 min). Such activity was blocked by injections of GABA and the GABA agonist, muscimol. Locomotion was induced by injection of substance P (SP), which also produced short, repeated episodes of locomotion. The more potent excitatory amino acid agonist, n-methyl-d-aspartic acid (NMDA), however, did produce dose-dependent, long-lasting (20 sec-5 min) locomotor episodes which were repeated over prolonged periods at the higher concentrations used (2-24 min). Additional injections of NMDA could drive stepping from a walk to a trot to a gallop. The effects of NMDA were blocked by injections of the excitatory amino acid antagonist, aminophosphonovalerionic acid (APV) (1-10 mM). Preliminary evidence suggests that carbachol (10-50 mM), a cholinergic agonist, inhibits NMDA-induced increases in muscle tone and episodes of stepping. The effect of carbachol was blocked by the cholinergic antagonist, atropine.

Animals↗

PubMed1990

Medioventral medulla-induced locomotion.

Previous anatomical studies demonstrated the presence of descending projections from the physiologically identified mesencephalic locomotor region (MLR) to the medioventral medulla (MED) in the cat. The present experiments were designed to determine if a similar low threshold locomotion-inducing area is present in the rat medulla. In addition, the nature of the neurochemical control of this area of the brain was explored using localized injections of neurochemical agents in the decerebrate rat during locomotion on a treadmill. A region virtually identical to that reported in the cat was found to lead to controlled locomotion on a treadmill following stimulation at low amplitude currents (less than or equal to 60 microA). Injections of cholinergic agonists into the MED of the rat induced locomotion which could be blocked by injections of cholinergic antagonists. In addition, injections of GABA antagonists were found to induce stepping which could be blocked by injections of GABA or GABA agonists. Substance P (SP) also was found to induce walking following injection into the MED of the rat. Injections of an excitatory amino acid agonist (NMDA) also were found to induce locomotion in the rat. These effects were blocked by injections of an excitatory amino acid antagonist (APV). Since these results had not been reported for the cat MED, a short series of experiments revealed that the MED in the cat also responded to NMDA.

Animals↗

PubMed1990

Characteristics of electrically induced locomotion in rat in vitro brain stem-spinal cord preparation.

1. Electrical stimulation of two brain stem regions in the decerebrate neonatal rat brain--the mesencephalic locomotor region (MLR) and the medioventral medulla (MED)--were found to elicit rhythmic limb movements in the hind-limb-attached, in vitro, brain stem-spinal cord preparation. 2. Electromyographic (EMG) analysis revealed locomotion similar to that observed during stepping in the adult rat. The step-cycle frequency could be increased by application of higher-amplitude currents; but, unlike the adult, alternation could not be driven to a gallop. 3. Threshold currents for inducing locomotion were significantly lower for stimulation of the MED compared with the MLR. Brain stem transections carried out at midpontine levels demonstrated that the presence of the MLR was not required for the expression of MED-stimulation-induced effects. 4. Substitution of the standard artificial cerebrospinal fluid (aCSF) by magnesium-free aCSF did not affect interlimb relationships and resulted in a significant decrease of the threshold currents for inducing locomotion. 5. Fixation of the limbs during electrical stimulation of brain stem sites altered the amplitude and duration of the EMG patterns, but the basic rhythm and timing of each muscle contraction during the step cycle was not affected. 6. These studies suggest that, although peripheral afferent modulation is evident in the neonatal locomotor control system, descending projections from brain stem-locomotor regions appear capable of modulating the activity of spinal pattern generators as early as the day of birth. However, there may be ceiling to the maximal frequency of stepping possible at this early age, perhaps suggesting a later-developing mechanism for galloping.

Animals↗

PubMed1989

Development of NADPH diaphorase-positive pedunculopontine nucleus neurons.

Nicotinamide adenine dinucleotide phosphate (NAD-PH) diaphorase histochemistry was used to localize cholinergic neurons in the pedunculopontine nucleus of neonatal and adult rats. Measurements of cell body areas revealed an average area around 200 microns2 at birth, followed by a significant increase to approximately 500 microns2 by 2 weeks of age. Thereafter, there was a decrease in cell area such that by 5 weeks of age the neurons had attained their adult size of around 300 microns2. The marked increase in cell size at the end of 2 weeks of age is discussed in relation to significant events in the development of locomotor and other rhythmic function control systems.

Aging↗