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E Garcia-Rill

Publications and source records attributed to E Garcia-Rill.

At least 73 records · Page 4Linked to original sources

Ascending projections of long descending propriospinal tract (LDPT) neurons.

Ascending projections of long descending propriospinal tract (LDPT) cells were investigated using the technique of double retrograde labeling. In rat, injection of one fluorescent dye was made into either the reticular formation or the cerebellum, and a second dye was injected into the lumbosacral enlargement (LSE). In cat, injections were made into the reticular formation and into the lumbosacral enlargement. Using fluorescence microscopy, observation of neurons in the cervical enlargement (CE) revealed single- and double-labeled cells which were either spinoreticular or spinocerebellar tract cells and/or LDPT cells. In both cat and rat, the location of double-labeled LDPT-spinoreticular cells were in the ventromedial spinal gray matter of the CE and were coextensive with single-labeled LDPT and spinoreticular cells. The locations of double-labeled LDPT-spinocerebellar cells in rat were in the ventromedial gray and were coextensive with single-labeled LDPT cells, but not with single-labeled spinocerebellar cells. The latter group was located in central lamina VII and medial laminae V and VI. Overall, the mean number of double-labeled cells was 40% of rat and 7% of cat LDPT cells, indicating projections to either the brainstem reticular formation or cerebellum as well as to the lumbosacral enlargement. Thus, a subpopulation of LDPT cells apparently also serves as a spinoreticular (SR) and spinocerebellar (SC) projection system.

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Electrically induced locomotion in the in vitro brainstem-spinal cord preparation.

Electrical stimulation of the brainstem was used to induce locomotion in the in vitro brainstem-spinal cord preparation. Recordings of electromyograms in 'limb-attached' preparations revealed an apparently adult-like step cycle. The lowest threshold sites were localized in the posterior midbrain (reticular formation in the peribrachial area and in the ventral reticular formation) and in the medioventral medulla (dorsolateral to the pyramids).

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Modulation of rhythmic function in the posterior midbrain.

Recordings of single unit activity in the posterior midbrain of the cat were carried out in the "fictive spontaneous locomotion" preparation. Neuronal activity was studied in relation to the onset, alternation and termination of cyclic hindlimb neurographic activity in the precollicular-postmammillary transected animal. Histochemical identification of pedunculopontine (nicotinamide adenine dinuceotide phosphate-diaphorase positive) neurons allowed the localization of recording sites in relation to this nucleus. Neurons located in the area of the cuneiform nucleus dorsal to the pedunculopontine nucleus were found to be related preferentially to cyclic (bursting) neurographic activity, while neurons in the area of the pedunculopontine were found to be related preferentially to the onset ("on") or termination ("off") of cycling episodes. Different populations of cells in the area appeared to be related to the frequency of alternation (bursting) compared with the duration of the cyclic episodes (on/off). While the area of the cuneiform-pedunculopontine nucleus has been found to be equivalent to the mesencephalic locomotor region, the same area has been found to be related to other rhythmic activities (e.g. respiratory, masticatory, sleep cycle, pressor, vesico-motor, etc.). A hypothesis is proposed to account for the weight of evidence implicating the same region in a host of distinct rhythmic activities. This hypothesis suggest that an oscillatory reverberation between cholinergic (pedunculopontine, laterodorsal tegmental nuclei) and aminergic (locus coeruleus, substantia nigra) centers is responsible for generating the various function-related "frequencies" (bursting) or "states" (on/off) of activity.

Action Potentials↗

The mesencephalic locomotor region. I. Activation of a medullary projection site.

Previous anatomical studies from our laboratories have demonstrated descending projections of the physiologically identified mesencephalic locomotor region (MLR) to the medioventral medulla. In the present study, this area was activated electrically and chemically to determine the nature of locomotor events elicited in the precollicular-postmammillary transected cat. Low-amplitude (less than 70 microA), high-frequency (5-60 Hz) stimulation of a specific region in the medioventral medulla elicited controlled episodes of locomotion on a treadmill. Injections of cholinergic agonists into this area also were found to elicit short episodes of locomotion. Injections of cholinergic antagonists were found to block locomotion elicited by: electrical stimulation of the same area; injections of cholinergic agonists; or electrical stimulation of the MLR. Injections of substance P into the medioventral medulla were found to induce locomotion for longer periods of time than injections of cholinergic agonists. These findings demonstrate physiologically that a primary caudal termination site of the MLR is located in the medioventral medulla, and suggest that at least a portion of descending MLR projections employ acetylcholine and substance P as neurotransmitters.

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The mesencephalic locomotor region. II. Projections to reticulospinal neurons.

Single neurons were recorded extracellularly in an area of the medioventral medulla known to receive descending mesencephalic locomotor region (MLR) input. A large number (47%) of these cells were found to receive short-latency orthodromic input following stimulation of the physiologically identified MLR. Of the medioventral medulla neurons studied, 34% were found to project to the spinal cord (determined by antidromic activation following stimulation of the ventrolateral funiculus). Approximately one-half (17% of the total population) of these reticulospinal cells were found to receive short-latency orthodromic input from the MLR. The regional distribution of this group of reticulospinal cells corresponded with the area found to receive descending projections from the MLR in previous anatomical studies. In addition, electrical and chemical activation of the same region was found to elicit locomotion on a treadmill in a companion study. The present findings demonstrate that descending MLR projections influence a large number of medioventral medulla cells, some of which have direct spinal projections, and suggest that this area is a primary relay in the manifestation of MLR function.

Action Potentials↗

Locomotion-inducing sites in the vicinity of the pedunculopontine nucleus.

The mesencephalic locomotor region (MLR) was identified physiologically by inducing controlled locomotion on a treadmill in the precollicular rat following application of low amplitude current pulses to areas of the pontomesencephalic tegmentum. The same brains were processed using either of two techniques known to label neurons of the pedunculopontine nucleus (PPN)-choline acetyltransferase (ChAT) immunocytochemistry or nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry. Histological reconstruction of locomotion-inducing sites were localized within or adjacent to ChAT or NADPH-diaphorase labeled cell groups. Three dimensional reconstructions of the PPN were used to visualize the colocalization of low threshold locomotion-inducing stimulation sites within PPN neuronal aggregates. These findings lend further support to the suggestion that the PPN is part of the MLR. A theoretical framework is proposed to account for results derived from various lines of research on this area.

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Projections of the mesencephalic locomotor region in the rat.

Retrograde labeling and electrophysiological techniques were used to determine the organization of efferent projections of the mesencephalic locomotor region (MLR) in the rat. Injections of horseradish peroxidase (HRP) or fluorescent dyes were made into suspected terminal zones of the MLR. After allowing for retrograde transport, the same animals underwent precollicular transection under anesthesia. The MLR was identified physiologically by the induction of controlled locomotion on a treadmill at low current (less than 50 microA) levels. Stimulation sites were marked and the brain processed accordingly. Retrogradely labeled cells in proximity (less than 0.5 mm) to locomotion-inducing stimulation sites were considered to be putative MLR neurons and were plotted according to stereotactic coordinates. These studies revealed the intrinsic organization of MLR neurons projecting to various brainstem sites. This organization may be related to the different types of transmitter systems involved in mediating MLR function.

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The basal ganglia and the locomotor regions.

This review cites evidence suggesting that the pedunculopontine nucleus (PPN), long known as a site of termination for basal ganglia outputs, is equivalent to the mesencephalic locomotor region (MLR), an area known to modulate spinal locomotion oscillators. The presence of cholinergic cells in this area also identifies it with the CH-5 cell group. In keeping with its cellular make-up, evidence is reviewed suggesting that the descending output of the PPN/MLR is cholinergic. This output may be under nigral GABAergic control which, in turn, may be under subthalamic influence. From various lines of evidence, it appears that the PPN/MLR receives elements of information from the motor cortex and basal ganglia centers involved in postural control. This area may be involved in the relay of information useful in the control of the center of gravity and other postural functions during locomotion. Pathological evidence is reviewed implicating basal ganglia afferents to the PPN/MLR (Parkinson's disease) and PPN/MLR efferents (Alzheimer's disease) in the deficits in locomotion observed in certain disorders.

Alzheimer Disease↗

Chemical activation of the mesencephalic locomotor region.

Electrical stimulation of the mesencephalic locomotor region (MLR) in the precollicular-postmammillary transected cat is known to induce controlled locomotion on a treadmill. We have been able to induce and block locomotion in this preparation by using localized infusions of transmitters and their agonists and antagonists. Infusions of the GABA antagonists bicuculline and picrotoxin into the MLR elicit locomotion at low concentration (5 mM). Applications of muscimol (5 mM) or GABA (0.5 M) were found to block chemically-induced locomotion, as well as electrically-elicited and spontaneous walking. Priming infusions of Diazepam amplified the blockage of locomotion by GABA. On the other hand, applications of strychnine (10 mM) were ineffective in inducing stepping, as were infusions of the excitatory agents glutamic acid, acetylcholine and norepinephrine. These findings suggest that the MLR is under inhibitory GABAergic input. The substantia nigra is the only known afferent to the MLR located posterior to the brainstem transection, and is a likely source for this input. A model is proposed to account for our results, as well as those of others, and it provides a working hypothesis for the neurochemical events occurring in brainstem centers which modulate locomotor events.

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The mesencephalic locomotor region (MLR) in the rat.

These studies demonstrate the presence of the MLR in the rat brain. Controlled locomotion on a treadmill could be induced by low level stimulation (less than 50 microA) of an area in the posterior midbrain following a precollicular-prenigral brainstem transection. This area included the lateral part of the cuneiform nucleus and anterior as well as posterior portions of the pedunculopontine nucleus. In addition, the presence of a subthalamic locomotor region in the fields of Forel was determined in rats after prethalamic transections.

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Interstitial nucleus of Cajal (INC) projections to the region of Probst's tract.

These studies were designed to investigate projections of the interstitial nucleus of Cajal (INC) to the region of the contralateral Probst's tract (PrTr). In electrophysiological experiments, INC neurons were antidromically activated from the contralateral PrTr, the medial longitudinal fasciculus (MLF) at medullary levels and the MLF at spinal cord levels. Some INC cells could be antidromically activated only from PrTr and others from both PrTr and the MLF. Anatomical experiments confirmed the existence of an INC projection into the region of the contralateral PrTr. Following injections of fluorescent dyes into the PrTr area, retrogradely labeled neurons were observed in the contralateral INC, with only occasional labeling ipsilaterally. Injections which included the medial vestibular nucleus labeled a greater number of INC cells ipsilaterally. After injections of dyes into the medullary MLF, retrogradely labeled cells were observed bilaterally in INC, although in greater numbers ipsilaterally. In experiments in which different dyes were injected into PrTr and the MLF, double labeled cells were found in the contralateral INC.

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Activity in the mesencephalic locomotor region during locomotion.

The activity of single neurons in the mesencephalic locomotor region (MLR) was recorded extracellularly in cats during spontaneous locomotion on a treadmill. Although stimulation of the MLR is required to induce locomotion on a treadmill after a precollicular-postmamillary brain stem transection in the cat, spontaneous locomotion may occur after a precollicular-premamillary transection. The activity of flexor and extensor muscles of each limb also was recorded by EMG. Nearly 50% of the MLR neurons exhibited rhythmic firing patterns during locomotion. In about one-half of those cells, unit firing patterns could be correlated with the EMG activity in one or more muscles by using spike-triggered averaging. Single MLR neurons were found to be correlated to EMG activity in a single limb, and others were related to the EMG from muscles in two limbs or in all four limbs. Passive movement or stoppage of the limb(s) did not abolish rhythmicity in these neurons. In addition, somatosensory stimulation did not appear to affect the firing patterns of MLR neurons. Averaged EMGs of correlated forelimb muscles revealed a postspike mean latency of 7.1 ms. These measurements agreed well with reports of a 1- to 1.5-ms delay in MLR projections to reticulospinal neurons and a 5- to 6-ms delay (postspike) in reticulospinal activity correlated to EMGs during locomotion. These findings suggest that (a) MLR neurons are rhythmically active during locomotion, (b) the activity of MLR neurons can be correlated with that of EMGs in one or more limbs, (c) rhythmicity in MLR neurons may be independent of phasic sensory input, and (d) the downstream influence of the MLR may be relayed, at least in part, via reticulospinal neurons.

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Connections of the mesencephalic locomotor region (MLR) I. Substantia nigra afferents.

These studies were designed to determine whether or not substantia nigra (SN) neurons project to the mesencephalic locomotor region (MLR). An attempt was made to activate SN neurons antidromically from the same site which induced locomotion on a treadmill following a precollicular-postmammillary transection in the same animal. Less than 10% of posterior SN neurons were activated antidromically from the physiologically-identified MLR. These results support previous anatomical findings describing a sparse projection from the SN to the MLR [5]. Locomotion on a treadmill was elicited at low current strengths (20-50 muA) from an area around the cuneiform nucleus in the posterior mesencephalon. This area included the lateral central gray, mesencephalic trigeminal root, dorsal brachium conjunctivum and nucleus tegmenti pedunculopontinus (NTPP) and perhaps anterodorsal locus coeruleus. Stimulation of the area just described induced a complete stepping cycle with a flexion phase and a three-part extension phase. Stimulation of the posterior SN produced spastic locomotion on a treadmill at higher current strengths (70 muA) in cats with a precollicular-postmammillary transection.

Afferent Pathways↗

Connections of the mesencephalic locomotor region (MLR) II. Afferents and efferents.

Injections of a tritiated amino acid-fluorescent dye mixture were made unilaterally into the area of the mesencephalic locomotor region (MLR). After allowing for retrograde and anterograde transport, the same site was electrically stimulated to induce locomotion on a treadmill following a precollicular-postmamillary transection. The tritiated amino acid transported anterogradely primarily was found autoradiographically to descend in the area of Probst's tract and to ascend to the centremedian nucleus (CM) of the thalamus. Neurons labeled retrogradely by the fluorescent dye in the same injection-stimulation site were observed in the substantia nigra, entopeduncular nucleus, sub- and hypothalamus and amygdala. In subsequent experiments, injections of fluorescent tracers were made into the area of Probst's tract and CM. Neurons in the mesencephalic trigeminal root, cuneiform nucleus, nucleus tegmenti pedunculopontinus (NTPP), dorsal locus coeruleus and lateral central gray were labeled from Probst's tract injections. Neurons in medial and lateral central gray, as well as NTPP, were labeled from CM injections.

Afferent Pathways↗

Connections of the mesencephalic locomotor region (MLR) III. Intracellular recordings.

The responses of neurons in the area of the cat mesencephalic locomotor region (MLR) following stimulation of the entopeduncular nucleus (EN) were recorded intracellularly. At the end of each experiment a precollicular-postmamillary brainstem transection was performed and stimulation of the recording site(s) was employed to induce locomotion on a treadmill. This procedure was assumed to establish that intracellularly studied cells in the vicinity of a locomotion-inducing site were MLR neurons. About 10% of MLR neurons were found to respond to stimulation of the EN at short latencies. Stimulation of MLR efferent pathways was used to identify output neurons by antidromic activation. Very few MLR output neurons were found to receive EN projections (i.e. to respond at short latency following EN stimulation). These experiments support previous results describing a sparse projection from the EN to the MLR. This projection appears to be functionally varied (EPSP, IPSP and EPSP-IPSP responses were observed in MLR neurons following EN stimulation) and to exert its major influence on interneurons, not on output neurons, of the MLR.

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Effects of electrical stimulation on acetylcholine synthesis in cat caudate nucleus.

The concentration of endogenous- and deuterium-labeled acetylcholine (ACh) in the cat caudate nucleus was determined after stimulation of either the substantia nigra or the precruciate cortex. In this procedure the caudate nucleus is exposed surgically, and a coring device is used to obtain biopsy specimens which are immediately frozen in liquid nitrogen. Samples are collected at rest, 5 min after stimulation, and again 5 min after a resting period. An infusion of 2H9-choline is maintained during these manipulations to provide a label for ACh synthesis. Electrical stimulation of the substantia nigra, which increases the release of dopamine, produced a decrease in endogenous ACh and the newly synthesized deuterium-labeled ACh. Stimulation of the precruciate cortex produced no significant effect on the levels or synthesis of ACh, but attenuated the effect of subsequent nigral stimulation. These preliminary results indicate that stimulation of the substantia nigra has a net excitatory effect on ACh synthesis in the caudate. This stimulation apparently is modulated by input from the cortex.

Acetylcholine↗

Effects of caudate nuclear or frontal cortical ablation in neonatal kittens or adult cats on the spontaneous firing of forebrain neurons.

In this paper we have determined the long-lasting consequences of caudate and frontal cortical lesions on spontaneous neuronal firing. Lesions were made both in neonatal and adult cats. All recordings were made in adults. Qualitatively, the effects of the caudate ablations were similar whether they had been carried out in kittens or in adult cats. Caudate lesions produced long-lasting (greater than or equal to 1 year) decreases in the spontaneous firing of cortical neurons. These changes were more pronounced when made in neonates than in adults. The distributions of mean interspike intervals were also altered by these caudate lesions in the pallidum and in the ventral lateral nucleus of the thalamus. Again these effects were more marked if the animals were lesioned as neonates than as adults. Frontal cortical lesions inflicted upon adult cats produced more widespread changes in spontaneous firing rates than similar lesions made in neonates. In both groups frontal lesions slowed spontaneous firing and changed the distributions of mean interspike intervals of caudate neurons. These effects were long-lasting (greater than or equal to 1 year in neonatally-ablated animals). Cortical lesions made in adult cats markedly altered thalamic and pallidal spontaneous activity. Similar lesions made in neonates produced relatively small changes in thalamic and pallidal activity.

Action Potentials↗

Pallidal projections to the mesencephalic locomotor region (MLR) in the cat.

The entopeduncular nucleus (EN) in the cat, homologue of the primate internal globus pallidus and main output of the basal ganglia, is known to project to the mesencephalic tegmentum. We have been able to elicit antidromic responses in single EN neurons from a site in the posterior mesencephalon, then transect the brainstem (precollicular-postmamillary) and elicit locomotion and rhythmic movements of the limbs by stimulation of the same site in the same animal. These studies demonstrate the existence of a direct projection from the EN to the mesencephalic locomotor region (MLR). However, this is not a particularly large pathway since fewer than 5% of the EN cells appear to project to the MLR. In a parallel series of anatomical experiments, injections of fluorescent dyes into the area of the MLR induced retrograde labeling of cell bodies in the EN and motor cortex. Injections of tritiated amino acids into the motor cortex resulted in labeling in the area anterior to the MLR. We assume that these connections may be involved, in part, in the sequencing and ordering of series of voluntary movements in which locomotion is involved.

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