Search PubMed⌕ Search

Biomedical subjects

L J Ryan

Publications and source records attributed to L J Ryan.

36 records · Page 2Linked to original sources
PubMed1987

Amphetamine alteration of amplitude and timing of cortical-neostriatal interactions.

Amphetamine (0.1 to 5.0 mg/kg, IV) altered frontal cortex stimulation evoked neostriatal potentials in rats. The amplitude of wave P1, which corresponds to an initial intracellular excitatory postsynaptic potential, was reduced, as was the latency to wave N3, which corresponds to the late rebound depolarization. Repetitive electric stimulation of the mesencephalic reticular formation at low currents (0.05 to 0.5 mA, 0.2-ms duration, 60 Hz square waves) produced similar effects. The peripherally acting sympathomimetics, norepinephrine (3 and 10 micrograms/kg, IV) and vasopressin (10 mU/kg, IV), increased blood pressure but did not alter the neostriatal evoked response. In rats with medial thalamic lesions induced by kainic acid, wave N3 was eliminated, and the effects of amphetamine and mesencephalic reticular formation stimulation on neostriatal evoked responses were reduced or eliminated. Thus many of the effects of systemic amphetamine on frontal cortex evoked neostriatal potentials may be mediated via extrastriatal sites, including the mesencephalic reticular formation and the medial thalamus.

Amphetamine↗
PubMed1986

Substantia nigra stimulation evoked antidromic responses in rat neostriatum.

Electrical stimulation of the substantia nigra of rats elicits a burst of small amplitude waves with a latency of 4-6 ms that may last for 10-15 ms throughout much of the neostriatum. Frontal cortex stimulation also elicits a burst response, which can occlude the substantia nigra response. The substantia nigra evoked burst response was still present after chronic neocortical ablation or thalamic transection or both treatments combined. The response corresponds to the first sharp negative wave of the substantia nigra evoked neostriatal field potential. Single substantia nigra evoked action potentials were recorded in neostriatum with a mean latency of 9.8 ms, ranging from 4-22 ms. These action potentials were considered to be antidromic because they were occluded during appropriate collision intervals by orthodromic action potentials elicited by frontal cortex stimulation. Subthreshold frontal cortex conditioning stimulation did not alter the threshold for activation from substantia nigra. The refractory period for the axon was at least as long as that for the soma and ranged between 0.8-2.0 ms. The antidromic responses failed to follow low frequency stimulation (less than 40 Hz for 3000 ms). This failure occurred in the axon between substantia nigra and globus pallidus. The burst response and first sharp negative wave of the field potential probably represent the antidromic activation of the ubiquitous and densely packed medium spiny neostriatal projection neurons. These responses occur at the same latency, respond in the same manner to twin pulse and repetitive stimulation and are occluded by frontal cortex stimulation in the same manner as antidromic action potentials.

Animals↗
PubMed1986

Frontal cortex stimulation evoked neostriatal potentials in rats: intracellular and extracellular analysis.

Evoked potentials, action potentials and intracellular events were recorded in the neostriatum of urethane anesthetized rats to electrical stimulation of frontal cortex white matter, motor cortex and pre-limbic cortex. Five major waves of the evoked potential were identified. Wave N1 (3.9 msec latency) was small, preceded cellular events and probably represents activation of corticostriate terminals. Wave P1 (10.8 msec latency to peak following white matter stimulation) coincided with an EPSP and neuronal firing. Both wave N2 (38.0 msec latency to peak) and P2 (approximately 110 msec duration) overlapped the intracellularly recorded hyperpolarization and inhibition of cell firing. Based upon this correspondence and upon the behavior of waves N2 and P2 with changing current and during conditioning-test paired pulse stimulation, it was concluded that the waves represent different processes contributing to the cellular hyperpolarization. A late wave, N3 (175 msec onset latency) corresponded to a late rebound firing and cellular depolarization. This late wave was eliminated from the neostriatum, but not from the overlying sensorimotor cortex, by kainic acid lesions that destroyed medial thalamus but left thalamic lateral nuclei and reticular nucleus intact.

Animals↗
PubMed1985

Amphetamine's effects on terminal excitability of noradrenergic locus coeruleus neurons are impulse-dependent at low but not high doses.

The actions of amphetamine in the locus coeruleus and its terminal fields in the frontal cortex were studied using extracellular recording to measure terminal excitability, firing rate and the probability of antidromic action potential invasion of the somatodendritic region in urethane anesthetized rats. At low dose (0.25 mg/kg), amphetamine increased terminal excitability. In comparison, subsequent administration of the highest dose (5.0 mg/kg, i.v.) of amphetamine tested suppressed neuronal firing and blocked antidromic action potential invasion of the somatodendritic region. Despite the absence of impulse traffic, high dose amphetamine reversed the effect of low dose amphetamine in the terminal field and decreased terminal excitability. The alpha 2 antagonist, yohimbine (0.5 mg/kg, i.v.), reversed the effects of high dose amphetamine on terminal excitability and somatodendritic invasion without reinstating neuronal firing. Noradrenergic autoreceptor agonists are known to decrease terminal excitability, whereas antagonists are known to increase terminal excitability. Thus, since low dose amphetamine produces the same effect on terminal excitability that antagonists do, it appears that low dose amphetamine may reduce autoreceptor activation by reducing norepinephrine release in frontal cortex as a consequence of inhibiting locus coeruleus neuronal firing. In contrast, high dose amphetamine acts like autoreceptor agonists do and decreased terminal excitability. Hence high dose amphetamine may increase norepinephrine release, even in the absence of impulse traffic.

Amphetamine↗
PubMed1985

Cholinergic regulation of neocortical spindling in DBA/2 mice.

Brief episodes of high-amplitude, bilaterally synchronous, seven-cycles-per-second spindles appear in the EEG of DBA/2 inbred mice during active waking, quiet waking, and slow-wave sleep. They do not occur during waking in C57BL/6 mice. This difference might result from differences in acetylcholine-mediated arousal as nicotine powerfully blocks brief spindle episodes in awake DBA/2 mice. The following results are reported. (i) Physostigmine (0.1 and 0.3 mg/kg, i.p.) desynchronized the EEG and produced behavioral immobility, but did not block brief spindle episodes in free-moving DBA/2 mice. (ii) Atropine (1.0 mg/kg, i.p.) reduced arousal and provoked slow waves without facilitating brief spindle episodes. (iii) Mecamylamine (1.0 mg/kg, i.p.) weakly activated spindles without producing any noticeable behavioral alterations. Because these treatments had little effect on spindle occurrence, the action of nicotine in brain stem-transected DBA/2 mice was investigated. Nicotine (1.0 mg/kg, i.p.) had no effect on brief spindle episodes released by rostropontine transection but powerfully blocked those provoked by pentylenetetrazol (20 mg/kg, i.p.) in midpontine-transected mice. Hence nicotine's antispindling action may be mediated in the rostral pons. As both nicotine and physostigmine produce behavioral immobility and EEG activation in free-moving DBA/2 mice, but only nicotine inhibits cortical spindling, the mechanisms that produce EEG desynchronization are probably not identical to those that prevent spindling. They may, though, be linked, parallel processes that are somehow dissociated in DBA/2 mice.

Animals↗
PubMed1985

Catecholamine regulation of neocortical spindling in DBA/2 mice.

The waking EEG of DBA/2 mice is punctuated by conspicuous bursts of high-amplitude, 6-7-cps spindles. Catecholamine depletion by 2.0 mg/kg, i.p., reserpine or 120 mg/kg, i.p., alpha-methyl-p-tyrosine increased the occurrence and duration of these brief spindle episodes (BSEs). This effect may reflect noradrenergic depletion because the beta-noradrenergic antagonist propranolol (10 mg/kg, i.p.) powerfully promoted BSE occurrence and increased BSE duration in freely-moving and midpontine-transected mice, whereas the dopamine antagonist haloperidol (2.0 mg/kg, i.p.) neither increased nor decreased BSE occurrence. The alpha-noradrenergic agonist clonidine (0.05 mg/kg, i.p.), which is known to inhibit noradrenergic neuronal firing as well as act at postsynaptic alpha receptors, also promoted BSE occurrence in transected mice. In addition, the dopamine agonist apomorphine (2.0 mg/kg, i.p.) increased BSE occurrence in freely-moving mice once the behavioral activation it produced subsided. These effects were blocked by 2.0 mg/kg haloperidol, i.p. The convulsant drug pentylenetetrazol, which is known to promote BSE occurrence at subconvulsant doses in DBA/2 mice, may activate BSEs, in part, by activating dopamine neurons: 2.0 mg/kg haloperidol, i.p., partially blocked the facilitation of BSEs by 20 mg/kg pentylenetetrazol, i.p., in midpontine DBA/2 mice. Thus, noradrenergic neurons may block spindle occurrence in DBA/2 mice whereas dopamine neurons may be one of several systems that can promote spindle occurrence.

Animals↗
PubMed1985

Neural mechanisms distinguishing the neocortical EEG of C57BL/6 mice from that of DBA/2 mice.

C57BL/6 inbred mice lack the 1-5 sec bursts of 6-7 cps spindles characteristic of the neocortical EEG of DBA/2 mice during waking. C57BL/6 mice (1) may be unable to generate any synchronized cortical EEG activity, (2) may lack the thalamocortical circuitry required to generate these brief spindle episodes (BSEs), (3) may lack mechanisms that can activate this circuitry or (4) may possess a potent mechanism to suppress BSE initiation and generation. Possibilities 1 and 2 have been eliminated because C57BL/6 mice generate pentobarbital, rostropontine-induced and sleep spindles, and because certain C57BL/6 sleep spindles resembled the BSEs seen in DBA/2 mice. Possibilities 3 and 4 were examined in the experiments reported here. In DBA/2 mice, pentylenetetrazol activates BSEs at subconvulsant doses. In contrast, neither 20 nor 50 mg/kg, IP, pentylenetetrazol activated BSEs in C57BL/6 mice, although the higher dose provoked 4-5 cps slow waves and myoclonic jerks. In DBA/2 mice, the beta-noradrenergic antagonist propranolol has been reported to powerfully release BSEs. In C57BL/6 mice, 10 and 15 mg/kg propanolol weakly released BSEs; fewer than 3 per hour occurred. Hence neither possibilities 3 and 4 are sufficient in themselves to explain the lack of BSEs during waking in C57BL/6 mice. However, simultaneous administration of 10 mg/kg propranolol and 20 mg/kg pentylenetetrazol provoked numerous BSEs in C57BL/6 mice. This suggests that perhaps C57BL/6 mice, as compared to DBA/2 mice, possess both a more powerful noradrenergic mechanism to suppress spindles and a more weakly functioning mechanism to activate BSEs. Hence possibilities 3 and 4 may both be correct.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Characterization of cortical spindles in DBA/2 and C57BL/6 inbred mice.

Continuous twenty-four hour EEG recordings were conducted on freely-moving DBA/2 and C57BL/6 inbred mice. No brief spindle episodes (BSEs: 6-7 cps, 1-5 sec duration, high amplitude spindle bursts) were seen in the waking EEG of C57BL/6 mice. BSEs were a conspicuous element of the EEG during active waking (AW) and quiet waking (QW) in DBA/2 mice. BSEs occurred at a 10X faster rate in QW than in AW and had a longer duration. Sleep spindle bursts resembling BSEs were seen in both C57BL/6 and DBA/2 mice, and occasionally were observed to follow a K-complex. Rostropontine, but not midpontine, brainstem transection released spindles in both strains. Pentobarbital produced spindles in both strains. The waveforms of the waves comprising BSEs, sleep spindles, transection-induced spindles and barbiturate spindles were quite similar, though differing in frequencies and amplitude. Genetic factors may be critical for the lack of BSEs during AW and QW in C57BL/6 mice and for the occurrence of BSEs during AW in DBA/2 mice. In contrast, most other rodents whow a third pattern: BSEs only during QW. Since C57BL/6 mice can generate spindles under some circumstances, the absence of spindles during waking reflects some alteration in the mechanisms that control the initiation of BSEs rather than a lack of the circuits required to generate a BSE. These mechanisms are distinct from those processes of arousal that produce the background EEG desynchronization of waking. Following both rostropontine and midpontine transection, the background EEG is desynchronized, yet after rostropontine, but not midpontine transection, BSEs occur freely, at a rate over 200 per hour.

Animals↗
PubMed1979

Techniques for the chronic cannulation of the jugular vein in mice.

The use of chronic intravenous cannulae implanted in the jugular vein of mice utilizing techniques previously developed for larger rodents is discussed. Two cannula designs and a chronic infusion chamber are illustrated. Cannula insertion depths for mice of three strains and various body weights, and estimates of operative mortality and cannula durability are given.

Animals↗
PubMed1979

Electrophysiological responses to ethanol, pentobarbital, and nicotine in mice genetically selected for differential sensitivity to ethanol.

Cortical electroencephalographic (EEG) changes induced by ethanol (4.3 and 1.4 g/kg, ip), pentobarbital (50 and 16 mg/kg), and nicotine (1.0 g/kg) were examined in long-sleep (LS) and short-sleep (SS) mice that were genetically selected for differential sleep times induced by a hypnotic dosage of ethanol. Ethanol (4.3 g/kg) caused EEG changes that paralleled the behavioral differences, whereas no differences between selected lines were observed following the activating dose (1.4 g/kg). Data support the notion that the known difference in ethanol sleep times is due not to greater SS sensitivity to ethanol activation but rather to greater LS sensitivity to ethanol hypnosis. No differences between selected lines were observed following 50 mg/kg pentobarbital, which again parallels previous behavioral data. The SS mice were more responsive to pentobarbital activation (16 mg/kg). Nicotine more severely reduced EEG power and heart rate in LS mice; a continuous iv infusion of nicotine elicited a distinct pattern of behavioral stereotypy for each selected line, with more profound motor and reflex depression in LS mice. The lines do not differ in rate of nicotine metabolism, hence they must differ in central nervous system sensitivity to nicotine. Thus, lines of mice selectively bred for differential sensitivity to ethanol also display marked differences in electrophysiological and behavioral responses to nicotine.

Animals↗
PubMedDate not supplied

Alteration of neuronal responses in the subthalamic nucleus following globus pallidus and neostriatal lesions in rats.

Kainic acid (2-4 days) or ibotenic acid (7-9 days) lesions of the globus pallidus or neostriatum altered the responsiveness of subthalamic nucleus neurons to electrical stimulation of the agranular frontal cortex. Three changes in responsiveness were seen following pallidal lesion: a) An increase in the proportion of responding cells as compared to controls (approximately 90% vs. 60%); b) an increase in the total duration of the evoked response (62.5 ms vs. 28.6 ms); 3) an increase in magnitude of response (9.76 spikes per stimulus vs. 3.24). Both an increase in firing rate (17.94 spikes/s vs. 8.23) and a change to a bursty spontaneous firing pattern were seen. Lesion of the neostriatum had fewer but opposite effects including decreased firing rate (7.21 spikes/s) and decreased total response duration (18.9 ms). These results suggest that the normal tonic inhibition of the subthalamic nucleus by the globus pallidus may play an important role in controlling subthalamic neuronal spontaneous activity and responsiveness. The neostriatum may influence the subthalamic nucleus via the globus pallidus. Globus pallidus lesions may have important consequences on the specificity of cortical control of the subthalamic nucleus and may alter subthalamic influence on basal ganglia output.

Animals↗