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Biomedical subjects

E Garcia-Rill

Publications and source records attributed to E Garcia-Rill.

At least 37 records · Page 2Linked to original sources
PubMed1999

Reduced sensory gating of the P1 potential in rape victims and combat veterans with posttraumatic stress disorder.

The P1 midlatency auditory evoked potential was studied in female rape victims with Posttraumatic Stress Disorder (PTSD) and compared to an age-matched female control group; and in male combat veterans with PTSD and compared to three groups of age-matched male control subjects. Sensory gating of the P1 potential was determined using a paired click stimulus paradigm in which the stimuli were presented at 250, 500 and 1000 msec interstimulus intervals (ISI). Results showed that sensory gating of the P1 potential was significantly decreased at the 250 msec ISI, and that there was a numerical, but not a statistically significant, decrease in sensory gating at the other intervals tested in both male and female PTSD subjects compared to all control groups. Since the P1 potential may be generated, at least in part, by the reticular activating system, dysregulation of sensory processing by elements of this system may be present in PTSD.

Acoustic Stimulation↗
PubMed1999

Neurochemical modulation of the P13 midlatency auditory evoked potential in the rat.

Previous studies have shown that the vertex-recorded P13 auditory evoked potential in the rat appears to be the rodent equivalent of the human P1 (or P50) potential. This sleep state-dependent potential appears to be generated, at least in part, by cholinergic pedunculopontine nucleus projections. The present studies used localized microinjections of neuroactive compounds into the region of the pedunculopontine nucleus in order to modulate the vertex-recorded P13 potential. Both the GABAergic agonist, muscimol, and the noradrenergic alpha2 receptor agonist, clonidine, were found to reduce the amplitude of the P13 potential in a dose-dependent manner. The suppressive effect of clonidine on P13 potential amplitude was blocked by pretreatment with the noradrenergic alpha2 receptor antagonist, yohimbine. In addition, habituation of the P13 potential, measured using a paired stimulus paradigm, was increased by micro-injection of a dose of muscimol or clonidine which did not change the amplitude of the P13 potential induced by the first stimulus of a pair. In contrast, microinjection of yohimbine decreased habituation of the P13 potential. These results show that the vertex-recorded P13 potential and its habituation can be modulated by activation of known inhibitory synapses, both GABAergic and noradrenergic, at the level of the pedunculopontine nucleus. This provides further evidence that the P13 potential is generated, at least in part, by pedunculopontine nucleus outputs.

Adrenergic alpha-Agonists↗
PubMed1998

Disinhibition of the sleep state-dependent p1 potential in Parkinson's disease-improvement after pallidotomy.

We previously reported that the P1 or P50 midlatency evoked potential underwent decreased habituation or disinhibition in patients with Parkinson's Disease. This sleep state-dependent response appears to be generated by cholinergic elements of the reticular activating system. We attempted to determine if the decreased habituation or disinhibition of the P1 potential would be altered by bilateral pallidotomy. Twenty-three patients who met inclusion criteria for surgery underwent pre- and post-operative evaluation using a Modified United Parkinson's Disease Rating Scale (UPDRS) and P1 potential recordings. Decreased habituation of the P1 potential was determined using a paired stimulus paradigm in which click stimuli were presented at 250, 500 and 1000 msec interstimulus intervals (ISI). Pre-operatively, patients showed disinhibition of the P1 potential at the 250 msec ISI (60 37% vs. 21 20%) and 500 msec ISI (78 47% vs. 43 31%) compared to age-matched control subjects. Post-operatively, the same patients showed a significant improvement in habituation of the P1 potential at the same ISIs (250 msec 37 21%; 500 msec 43 32%). UPDRS scores for these patients pre-operatively were 59 18 and 24 11 post-operatively, resulting in a significant reduction in symptom severity. We conclude that bilateral pallidotomy resulted in a significant improvement in symptom ratings and reduced the disinhibition of the P1 midlatency evoked response.

Analysis of Variance↗
PubMed1997

Developmental changes in serotonergic receptor-mediated modulation of embryonic chick motoneurons in vitro.

Intracellular recordings were obtained from antidromically identified motoneurons in an embryonic chick spinal cord slice preparation at two developmental stages (embryonic days 12 and 18, E12 and E18) which bracket a critical period in spinal cord growth. The resting membrane potential of chick motoneurons did not change significantly between E12 and E18, but there was a significant decrease in neuronal input resistance. A small inward rectification was present in cells of both ages, although a lower proportion of E12 motoneurons exhibited inward rectification compared to E18 motoneurons. Injection of depolarizing current pulses revealed that most E12 motoneurons exhibited spike adaptation, while the majority of E18 motoneurons showed high frequency tonic firing. Bath application of serotonin (5-HT) and its agonists 5-carboxamido-tryptamine (5-CT, a 5-HT1 agonist) and alpha-methyl 5-HT (a 5-HT2 agonist) produced hyperpolarizing responses accompanied by decreased input resistance in all E12 motoneurons studied. The same three agonists produced depolarizing responses and increased input resistance in all E18 motoneurons studied. The effects of serotonergic agonists on motoneuronal excitability were tested using depolarizing current pulses. In most cases, serotonergic agonists caused a decrease in firing frequency during the hyperpolarizing response in E12 neurons. At E18, bath application of 5-HT, 5-CT or alpha-methyl 5-HT produced an increase in firing frequency in all motoneurons during the depolarizing response. Our results indicate that both 5-HT1 and 5-HT2 receptor subtypes contribute to modulation of chick motoneuron excitability and appear to reverse the polarity of their effects on membrane potential after a critical period in development of the spinal cord.

Analysis of Variance↗
PubMed1997

Decreased habituation of midlatency auditory evoked responses in Parkinson's disease.

The P1 midlatency auditory evoked potential was studied in patients with Parkinson's disease and compared to that in age-matched controls. Habituation of the potential was determined by using a two-click stimulus paradigm in which the stimuli were presented at 250-, 500-, and 1,000-ms interstimulus intervals. Results showed that habituation of the P1 potential had a statistically significant decrease at the 250-ms and 500-ms interstimulus intervals in patients with Parkinson's disease compared to normal controls. The degree of decreased habituation was found to increase with severity of the disease such that stage 5 patients showed greater decreases in habituation compared to stage 4, as did stage 4 compared to stage 3. These findings may be explained by the presence of a dysregulation of sensory processing, possibly by elements of the reticular activating system, including the pedunculopontine nucleus, in Parkinson's disease.

Aged↗
PubMed1997

Combat veterans with posttraumatic stress disorder exhibit decreased habituation of the P1 midlatency auditory evoked potential.

The current study used a paired stimulus paradigm to investigate the P1 midlatency auditory evoked potential in Vietnam combat veterans with posttraumatic stress disorder (PTSD) and three comparison groups: alcohol dependents, combat-exposed normals, and combat-unexposed normals. Compared to each comparison group, PTSD subjects exhibited significantly diminished habituation of the P1 potential. P1 potential habituation within the PTSD group, correlated significantly with intensity of PTSD reexperiencing symptoms, such as trauma-related nightmares and flashbacks. These findings are discussed as consistent with a sensory gating defect at the brainstem level in PTSD, and are further discussed in the context of other psychophysiological measures in PTSD and of P1 potential findings in psychiatric disorders other than PTSD.

Analysis of Variance↗
PubMed1997

Disorders of the reticular activating system.

The organization of components of the reticular activating system and their role in sleep-wake mechanisms and arousal are described. A functional model is proposed based on known neuroanatomical and neurophysiological findings. The involvement of these elements of the reticular activating system in various neurological and psychiatric disorders is discussed. A series of hypotheses are advanced to account for the role of these nuclei in such diverse disorders as schizophrenia, post-traumatic stress disorder, REM behavior disorder, Parkinson's disease and narcolepsy. This line of reasoning suggests that, when neurological or psychiatric disorders manifest symptoms related to arousal and sleep-wake control, disturbances of elements of the reticular activating system must be considered responsible.

Animals↗
PubMed1996

Effects of exercise and fetal spinal cord implants on the H-reflex in chronically spinalized adult rats.

This study investigated the modulation of hindlimb reflex excitability after transection of the spinal cord in adult rats. After transection, the H-reflex exhibited decreased depression at high stimulation frequencies compared to intact animals. Groups of animals which received a spinal cord transection followed by either an exercise regimen for the hindlimbs or a fetal spinal cord implant, showed high stimulation frequency depression similar to controls. This suggests that each of these palliative strategies helped to "normalize' the excitability of specific spinal reflexes.

Animals↗
PubMed1996

HLA class II genes associated with REM sleep behavior disorder.

Twenty-five white men with rapid eye movements (REM) sleep behavior disorder, but without narcolepsy, underwent HLA class II antigen typing: 84% (N=21) were DQwl (DQB1*05,06) positive (28% [N=7] were DR2 positive); DQB1*0501 (N=9) and DQB1*0602 (N=7) were the most common phenotypes. The 84% DQwl rate in men with REM sleep behavior disorder was significantly greater (p=0.015) than the 56% DQwl rate found in a local white comparison group (N=66), and was greater than the 39 to 66% DQwl rates published for 12 white groups (N=40-418/group). Thus, another disorder of REM sleep dysregulation (besides narcolepsy) appears to be strongly associated with specific HLA class II genes.

Electromyography↗
PubMed1996

Synaptic evoked potentials from regenerating dorsal root axons within fetal spinal cord tissue transplants.

Previously injured dorsal roots were electrically stimulated to determine if regenerating sensory axons can form physiologically active synaptic contacts with neurons within fetal spinal cord tissue transplants. Dorsal rootlets, sectioned at their spinal cord entry zone, were apposed to intraspinal transplants of fetal spinal cord tissue grafted along each side of a nerve growth factor treated nitrocellulose implant. Two to six months later, the rootlets were transected between the spinal cord and their respective ganglia and electrically stimulated. Evoked potentials were recorded from the dorsal surface of the transplant, but were absent from adjacent ipsilateral and contralateral spinal cord regions. A glass micropipette was advanced through the transplant and used to record intramedullary field potentials evoked by dorsal root stimulation. Maximal negative potentials occurred 400-700 micron below the dorsal surface of the transplant, shifting to positive potentials deeper into the transplant. Additionally, both spontaneous and electrically evoked single neuronal action potentials were observed along the microelectrode track. Evoked potentials were abolished following transaction of the rootlets between the stimulation site and the transplant. Immunocytochemical evidence of the production of fos protein following electrical stimulation of the regenerated dorsal rootlets was demonstrated within transplant neurons and some ventrally located host neurons, providing an anatomical correlate to the electrophysiological recordings of synaptic activation. These results provide evidence of the structural and functional integration of regenerated sensory axons with both transplant and host neurons.

Animals↗
PubMed1996

Midlatency auditory evoked potentials and the startle response in the rat.

The P13 midlatency auditory evoked potential in the rat is (i) sleep state dependent, (ii) undergoes rapid habituation and (iii) is blocked by the cholinergic antagonist scopolamine. As such, the P13 potential in the rat shows the same characteristics as the P1 (or P50) potential in the human. These potentials are thought to be mediated, at least in part, by the cholinergic arm of the reticular activating system. Previous studies have linked the reticular activating system with the startle response. The present study was undertaken to explore this relationship by simultaneously recording the P13 potential and the electromyographically recorded startle response using stimuli designed to elicit each response. Simultaneous recordings from the vertex and neck musculature following auditory click stimuli showed that: (i) the mean threshold of the P13 potential was 69.3 +/- 1.9 dB, while that for the startle response was 87.9 +/- 6.4 dB; (ii) the P13 potential was present during waking and paradoxical sleep, but absent during slow-wave sleep, while the startle response was present reliably only during waking; (iii) both responses habituated in response to paired stimuli, but the startle response was more habituated than the P13 potential; and (iv) both responses were facilitated by trains of stimuli in a similar manner. Recordings carried out from the auditory cortex verified that the primary cortical response had properties different from the P13 potential; i.e. it was present during all sleep-wake states, had a lower threshold and did not habituate rapidly. Finally, different patterns of startle responses were detected in the neck muscles. In every case, the P13 potential occurred during the middle, inhibitory phase of the startle response. These results suggest that the P13 potential and the startle response share response features, but the P13 potential appears to be more sensitive to auditory stimulation and to sleep-wake states. The startle response may be modulating descending systems by priming the spinal cord to respond in a "fight vs flight" fashion. On the other hand, the P13 response may be modulating ascending systems by triggering thalamocortical activity and resetting descending systems to allow novel motor strategies.

Animals↗
PubMed1996

Developmental changes in the effects of serotonin and N-methyl-D-aspartate on intrinsic membrane properties of embryonic chick motoneurons.

A spinal cord slice preparation was developed in order to study developmental changes in intrinsic membrane properties and in responses to N-methyl-D-aspartate and serotonin in embryonic chick motoneurons. Transverse spinal cord slices were obtained from chick embryos over a series of developmental stages (embryonic days 12-18). Intracellular recordings were obtained from 87 antidromically identified motoneurons. During the stages examined, the average resting membrane potential did not vary significantly, the voltage threshold of current-evoked action potentials became significantly more negative, there was a non-significant trend towards a decrease in the recorded input resistance, but there were no significant changes observed in the membrane time constant. There were significant developmental changes in the waveform of the current-evoked action potentials. The average amplitude of the action potentials increased over the stages studied, while the action potential duration measured at half-amplitude decreased. All of the motoneurons examined were maximally depolarized by bath application of 50 microM N-methyl-D-aspartate. The depolarization persisted in the presence of tetrodotoxin but was blocked by 100 microM 2-amino-5-phosphonopentanoic acid and, therefore, was at least partially due to a direct action of N-methyl-D-aspartate on motoneuronal receptors. The average amplitude of the N-methyl-D-aspartate-induced depolarizations decreased significantly over the stages examined. In contrast, bath application of 50 microM serotonin produced either depolarizing or hyperpolarizing responses depending on the developmental age of the motoneuron. Serotonin induced a depolarization in about 50% of the motoneurons at embryonic day 12, 69% of the motoneurons at embryonic day 15 and 100% of the motoneurons recorded from at embryonic day 18. These findings reveal important developmental changes in intrinsic membrane responses and action potential properties of chick motoneurons recorded from a slice preparation. We have also documented changes in the motoneuronal responses to serotonin, a neurotransmitter used by a major descending projection, and N-methyl-D-aspartate, which activates glutamate receptors known to contribute to synaptic activity in segmental circuits.

Action Potentials↗
PubMed1995

The pedunculopontine nucleus--auditory input, arousal and pathophysiology.

This review describes the role of the pedunculopontine nucleus (PPN) in various functions, including sleep-wake mechanisms, arousal, locomotion and in several pathological conditions. Special emphasis is placed on the auditory input to the PPN and the possible role of this nucleus in the manifestation of the P1 middle latency auditory evoked response. The importance of these considerations is evident because the PPN is part of the cholinergic arm of the reticular activating system. As such, the auditory input to this region may modulate the level of arousal of the CNS and, consequently, abnormalities in the processing of this input can be expected to have serious consequences on the level of excitability of the CNS. The involvement of the PPN in such disorders as schizophrenia, anxiety disorder and narcolepsy is discussed.

Animals↗
PubMed1995

Mesopontine neurons in schizophrenia.

Findings reported here show that there is a significant increase in the number of neurons in the pedunculopontine nucleus in most schizophrenic patients compared to age-matched controls. Nicotinamide adenine dinucleotide phosphate diaphorase histochemistry was used to label putative cholinergic neurons in the pedunculopontine nucleus and laterodorsal tegmental nucleus, while noradrenergic locus coeruleus neurons were labeled immunocytochemically using an antibody to tryosine hydroxylase. Cell counts of these neuronal groups were carried out using a Biographics image analysis system. We found significantly increased cell numbers in the pedunculopontine nucleus of schizophrenic patients compared to controls. The number of laterodorsal tegmental nucleus neurons was increased but this was not statistically significant. However, the total cell counts for pedunculopontine and laterodorsal tegmental nuclei were significantly higher in schizophrenic subjects. The number of locus coeruleus noradrenergic neurons was similar in both groups. These results implicate the brainstem reticular formation as a pathophysiological site in at least some patients with schizophrenia. In addition, these findings suggest a developmental etiology for the disease and account for some, but not all, of the symptoms of schizophrenia, including sensory gating abnormalities, sleep-wake disturbances and, perhaps, hallucinations. Overdriving of thalamic and substantia nigra function by cholinergic afferents from the midbrain may account for some of the symptoms seen in schizophrenia. These findings suggest that, at least in some schizophrenic patients, there is an increased number of neurons in the cholinergic arm of the reticular activating system. This may explain some of the symptoms of schizophrenia and points to a prenatal disturbance as one of the possible causes of the disease.

Aged↗
PubMed1995

Auditory input to the pedunculopontine nucleus: II. Unit responses.

The pedunculopontine nucleus (PPN) has been implicated in sleep-wake control, arousal responses, and motor functions. The PPN also has been implicated in the generation of the P1 middle-latency auditory-evoked potential. The present study was undertaken to determine the nature of the responsiveness of single neurons in and around the PPN following auditory stimulation. Somatosensory responsiveness also was tested in some cells. These results demonstrate a) the presence of a significant proportion of PPN neurons that respond to auditory click stimuli; b) two populations of neurons showing either low threshold/short latency/low habituation or high threshold/longer latency/high habituation; c) the responses of longer latency neurons precede the onset and peak of depth- and vertex-recorded middle-latency auditory-evoked potentials; d) thresholds of longer latency neurons similar to the threshold for wave A in the intact cat, the P13 potential in the intact rat, or the startle reflex; and e) convergent somatosensory and auditory responses at a similar latency in a number of PPN neurons. These findings suggest that neurons in and around the PPN may participate in auditory and somatosensory information processing related to arousal, and may contribute to the manifestation of the P1 auditory middle-latency evoked potential.

Acoustic Stimulation↗
PubMed1995

Auditory input to the pedunculopontine nucleus: I. Evoked potentials.

The pedunculopontine nucleus (PPN) has been implicated in sleep-wake control, arousal responses, and motor functions. The PPN also has been implicated in the generation of the P1 middle-latency auditory-evoked potential. The present study was undertaken to determine the topographical distribution, threshold, and response properties of depth-recorded potentials following auditory click stimulation. Experiments were conducted in both decerebrate cat and rat, with a view towards determining the presence of P1-like middle-latency auditory-evoked potentials in the midbrain of both species. These results demonstrate a) the presence in and around the PPN of a P1-like potential in the decerebrate rat similar to that described in the accompanying article as the P13 in the intact rat; b) the presence in and around the PPN of a P1-like potential in the decerebrate cat similar to that previously described by others as wave A in the intact cat; c) although thresholds for these potentials were similar to those of intact preparations, following frequencies were higher in the decerebrate preparations, i.e., responsiveness to repetitive stimulation was higher; and d) depth-recorded somatosensory-evoked potentials also were studied in the cat and found to show an evoked potential at a similar latency as middle-latency auditory depth-recorded potentials. These findings suggest that click stimulus-evoked, depth-recorded potentials are present in and around the PPN in the decerebrate rat and cat, i.e., in the absence of cortex, at a similar latency as in intact preparations.

Acoustic Stimulation↗