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P M Groves

Publications and source records attributed to P M Groves.

At least 55 records · Page 3Linked to original sources
PubMed1988

Continuous amphetamine administration induces tyrosine hydroxylase immunoreactive patches in the adult rat neostriatum.

Continuous 3-day administration of d-amphetamine sulfate via a subcutaneous minipump induced the appearance of tyrosine hydroxylase immunoreactive patches in the neostriatum of adult Sprague-Dawley and Long-Evans rats at doses (greater than 20 mg/kg/day) that also produced axonal terminal degeneration as evidenced by Fink-Heimer silver grain deposition. The tyrosine hydroxylase patches coincided with striosomes identified by Leu-enkephalin immunoreactivity on adjacent sections. Sham-operated control, naive control, low dose amphetamine- (less than 15 mg/kg/day) and cocaine- (less than 125 mg/kg/day, IV) treated rats did not show tyrosine hydroxylase neostriatal patches nor axonal degeneration. These results suggest that the diffuse neostriatal dopamine system may be more susceptible to the neurotoxic, degenerative action of continuously administered amphetamine than is the islandic dopamine system.

Animals↗
PubMed1988

Three-dimensional pattern of enkephalin-like immunoreactivity in the caudate nucleus of the cat.

Recent anatomical investigations of the mammalian neostriatum have uncovered discrete neurochemical zones characterized by low levels of AChE and high levels of enkephalin-like immunoreactivity (ELI) compared with the surrounding neostriatal tissue. These regions, termed striosomes, which appear as patches in individual sections, have been associated with specific afferent and efferent pathways that differ from those of the surrounding neostriatal tissue. In the present study, the 3-dimensional distribution of these enkephalin-rich compartments in the caudate nucleus of the adult cat was investigated using computer-assisted 3-dimensional reconstruction techniques. Series consisting of coronal, sagittal, and horizontal tissue sections were obtained. In individual sections, discrete patches of intense enkephalin-like immunoreactivity appeared against a lighter-staining background. Three-dimensional reconstructions revealed that these patches overlapped across sections to form a highly inter-connected structure within the head and body of the caudate nucleus. Several structural features were evident in these reconstructions that appeared to be similar across animals. One consistent pattern was the formation of enkephalin-labeled finger-like structures radiating from the ventricular edge diagonally across the width of the nucleus. Smaller crossbridges were seen connecting the fingers, which often resulted in the formation of claws or rings of enkephalin-like immunoreactivity. These elements appear to align across planes to form a lattice-like structure outlining continuous regions of matrix. This structure may provide a basis for the orderly interaction between the patch and matrix compartments.

Animals↗
PubMed1987

Acute ultrastructural and behavioral effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice.

Acute actions of MPTP on behavior and on neostriatal ultrastructure were examined in young C57 Black mice. Autonomic, motor, and toxic effects of MPTP exhibited dependence on dose (20-40 mg/kg) and time during the first 4 h after subcutaneous injection. The ultrastructure of the neostriatum was altered very quickly (2-24 h) after single injections of MPTP. Darkened glial processes were found within 2-8 h, followed by dark degeneration of synaptic boutons, especially those making small symmetric synapses. More rarely, swollen axons and postsynaptic degeneration were also observed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Do antidromic latency jumps indicate axonal branching in nigrostriatal and hypothalamo-neurohypophysial neurons?

Neurons in many brain regions exhibit discontinuous decreases in antidromic latency with small increases in stimulating current. We used an electrophysiological test requiring a single stimulating electrode to determine whether these 'latency jumps' are due to shifts in the site of spike initiation to the same or different axon branches. Latency jumps in response to stimulation of the striatal terminal fields of substantia nigra, pars compacta neurons represent spike initiation on different branches while those seen in paraventricular neurons with pituitary stalk stimulation usually reflect a change in site on a single branch.

Animals↗
PubMed1987

Relation of pontine choline acetyltransferase immunoreactive neurons with cells which increase discharge during REM sleep.

The purpose of this study was to determine whether neurons in the medial pontine reticular formation with high discharge rates during REM sleep could be localized in regions of the brainstem having neurons displaying choline acetyltransferase immunoreactivity. Six cats were implanted with sleep recording electrodes and microwires to record extracellular potentials of neurons in the pontine reticular formation. Single-units with a S:N ratio greater than 2:1 were recorded for at least two REM sleep cycles. A total of 49 units was recorded from the pontine reticular formation at medial-lateral planes ranging from 0.8 to 3.7 mm. The greatest proportion of the units (28.6%) showed highest discharge during active waking and phasic REM sleep compared to quiet waking, non-REM sleep, transition into REM sleep or quiet REM sleep periods. A percentage (20.4%) of the cells had high discharge associated with phasic REM sleep periods while 8.2% of the cells showed a progressive increase in discharge from waking to REM sleep. Subsequent examination of the distribution of choline acetyltransferase immunoreactive cells in the PRF revealed that cells showing high discharge during REM sleep were not localized near presumed cholinergic neurons. Indeed, we did not find any ChAT immunoreactive somata in the medial PRF, an area which has traditionally been implicated in the generation of REM sleep. These results suggest that while increased discharge of PRF cells may be instrumental to REM sleep generation, these cells are not cholinergic.

Animals↗
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↗
PubMed1987

Electrophysiologically identified nigral dopaminergic neurons intracellularly labeled with HRP: light-microscopic analysis.

Intracellular recordings were obtained in vivo from neurons of the rat substantia nigra, pars compacta. Neurons that were identified as dopaminergic by a variety of electrophysiological criteria, including antidromic activation from ipsilateral neostriatum or globus pallidus, were microiontophoretically injected with horseradish peroxidase and examined at the level of the light microscope. Dopaminergic neurons were of medium size and had ovoid, polygonal, or fusiform cell bodies that emitted from 3-6 primary dendrites. Much of the sparse and relatively unbranched dendritic arborization of these neurons remained within pars compacta, except for 1 or 2 large dendrites that were directed ventrally or ventrolaterally into pars reticulata, roughly perpendicular to the plane of the pars compacta. In coronal sections, the dendrites of ovoid- or polygonal-shaped pars compacta neurons were oriented mainly along the dorsoventral axis, whereas fusiform-shaped neurons had dendrites that were oriented primarily mediolaterally. Although some of the dendrites of dopaminergic neurons exhibited variations in diameter, most were not markedly varicose. Dendrites were sometimes sparsely invested with spinelike appendages or other dendritic extrusions, particularly along their distal portions. The axons of dopaminergic pars compacta neurons were emitted from primary or proximal secondary dendrites, and were extremely fine processes, 0.5 micron or less in diameter. No local axon collaterals were observed.

Animals↗
PubMed1986

Autoreceptor-mediated changes in dopaminergic terminal excitability: effects of potassium channel blockers.

The effects of the potassium channel blockers, 4-aminopyridine (4-AP) and tetraethylammonium (TEA), on autoreceptor-mediated changes in dopaminergic terminal excitability were examined in urethane-anesthetized rats. Local infusions of 4-AP or TEA into neostriatal terminal fields of nigral dopaminergic neurons led to marked decreases in terminal excitability, as measured by the increase in stimulating current required to activate the neurons antidromically from the site of the infusion. The decreased excitability resulting from 4-AP could be reversed by subsequent i.v. injection of haloperidol, and was blocked in rats that had been depleted of endogenous dopamine by prior treatment with alpha-methyl-p-tyrosine (AMpT). Thus, the decrease in excitability elicited by the potassium channel-blockers was indirect, and apparently due to increased autoreceptor stimulation resulting from enhanced transmitter release. In addition, co-infusion of 4-AP and apomorphine in AMpT-treated animals led to decreased terminal excitability that did not differ from the effects of apomorphine alone, indicating that 4-AP did not block the effects of exogenous autoreceptor agonist administration. These results provide in situ electrophysiological evidence that autoreceptor-mediated processes occurring at dopaminergic terminals are not mediated by 4-AP- or TEA-sensitive potassium channels. Furthermore, our findings suggest that, as in other types of presynaptic terminals, blockade of voltage-sensitive potassium channels in dopamine terminals leads to enhanced release of transmitter.

4-Aminopyridine↗
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

Antidromic activation of dorsal raphe neurons from neostriatum: physiological characterization and effects of terminal autoreceptor activation.

Three types of neurons, distinguished on the basis of their spontaneous firing rates and patterns, extracellularly recorded waveforms and responses to neostriatal stimulation, were observed in the dorsal raphe nucleus in urethane-anesthetized rats. Type 1 neurons (presumed to be serotonergic) fired spontaneously from 0.1 to 3 spikes/s in a regular pattern, with initial positive-going bi- or triphasic action potentials. Type 1 cells exhibited long-latency antidromic responses to neostriatal stimulation (mean +/- S.E.M. 24.9 +/- 0.3 ms) that sometimes occurred at discrete multiple latencies, and supernormal periods persisting up to 100 ms following spontaneous spikes. Type 2 cells fired spontaneously in an irregular, somewhat bursty pattern from 0 to 2 spikes/s with initial negative-going biphasic spikes, and were antidromically activated from neostriatal stimulation at shorter latencies than Type 1 cells (21.8 +/- 0.9 ms). Type 3 cells were characterized by initial positive-going biphasic waveforms and displayed a higher discharge rate (5-30 spikes/s) than Type 1 or Type 2 cells. Type 3 cells could not be antidromically activated from neostriatal stimulation. The relatively long conduction time to neostriatum of the Type 1 presumed serotonergic neuron is discussed with respect to previous interpretations of the synaptic action of serotonin in the neostriatum. In conjunction with these antidromic activation studies, the neurophysiological consequences of serotonergic terminal autoreceptor activation were examined by measuring changes in the excitability of serotonergic terminal fields in the neostriatum following administration of the serotonin autoreceptor agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). The excitability of serotonergic terminal fields was decreased by intravenous injection of 40 micrograms/kg 5-MeODMT, and by infusion of 10-50 microM 5-MeODMT directly into the neostriatum. These results are interpreted from the perspective of mechanisms underlying autoreceptor-mediated regulation of serotonin release.

Animals↗
PubMed1984

Autoreceptor-mediated changes in dopaminergic terminal excitability: effects of increases in impulse flow.

The effect of spontaneous and stimulation-induced alterations in impulse flow on the antidromic excitability of nigrostriatal dopaminergic neurons were investigated in urethane-anesthetized rats. Terminal excitability was found to be inversely related to the rate of spontaneous activity of nigral neurons. Conditioning stimulation applied to dopaminergic axons in the medial forebrain bundle was found to decrease terminal excitability, but axonal conditioning stimulation was without effect on antidromic responses evoked from the medial forebrain bundle. Decreases in terminal excitability induced by medial forebrain bundle stimulation could be blocked by local infusions of haloperidol into the region of the terminal fields, suggesting that the effect was receptor-mediated. These results are consistent with the proposal that nigrostriatal dopaminergic neurons may modulate the impulse-dependent release of dopamine from striatal nerve terminals as a function of firing rate by autoreceptor-mediated alterations in the electrical properties of the terminal membrane.

Animals↗
PubMed1984

Autoreceptor-mediated changes in dopaminergic terminal excitability: effects of striatal drug infusions.

The neurophysiological correlates of autoinhibition at the terminals of nigrostriatal dopaminergic neurons were studied by measuring the changes in antidromic excitability of nigrostriatal neurons following local infusions of various catecholamine agonists and antagonists into the neostriatum. Infusions of apomorphine or amphetamine reduced terminal excitability whereas the dopamine antagonists, haloperidol, fluphenazine or sulpiride, led to increases in terminal excitability. Alterations in antidromic excitability were constrained to the terminal regions and were not observed when infusions and excitability testing were performed in the medial forebrain bundle. The alpha-2 agonist, clonidine, did not alter dopaminergic terminal excitability. Our results indicate that pharmacological manipulations which have been shown to reduce the amount of stimulation-induced transmitter release from dopaminergic terminals are associated with a dopamine autoreceptor-mediated hyperpolarization and/or alteration in ionic conductance of the terminal membranes. These results are discussed with respect to mechanisms of autoinhibition in the central nervous system.

Animals↗
PubMed1983

Dendro-dendritic synapses in substantia nigra: descriptions based on analysis of serial sections.

Dendro-dendritic synapses were studied in serial sections of rat substantia nigra in subjects pretreated with intraventricularly administered 5-hydroxydopamine, a monoaminergic synaptic label. These synapses had symmetrical membrane thickenings and small clusters of heavily labeled pleomorphic vesicles in the presynaptic dendrites, which were assumed to extend from the dopaminergic cells of pars compacta. Dendro-dendritic synapses were seen in the pars compacta of the substantia nigra, but were not found in blocks trimmed to include only the nondopaminergic pars reticulata. The presynaptic dendrites did not receive other synapses near the sites of dendro-dendritic synapses. These dendrites were frequently apposed to other dendrites for long distances with no intervening glial processes. In many cases, several adjacent dendro-dendritic contacts were made by a single presynaptic dendrite onto several different postsynaptic dendrites. Presynaptic dendrites did not participate in reciprocal synapses, serial synapses, or dendro-axonic synapses. Presynaptic and postsynaptic dendrites engaged in dendro-dendritic synaptic contact were of similar appearance and both had cross-sectional diameters of 0.23-1.9 microns. In several cases, label could also be detected in the postsynaptic dendrite in cisternae of smooth endoplasmic reticulum, providing evidence for dendro-dendritic synapses between dopaminergic neurons. Release of dopamine from dopaminergic dendrites and their role in the control of neuronal activity in substantial nigra are discussed.

Animals↗