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P M Groves

Publications and source records attributed to P M Groves.

At least 73 records · Page 4Linked to original sources
PubMed1983

A theory of the functional organization of the neostriatum and the neostriatal control of voluntary movement.

A theory of the intrinsic, functional organization of the neostriatum and the neostriatal control of voluntary movement is presented. The cell types of neostriatum are described in accordance with the classification scheme of Pasik, Pasik and DiFiglia (ref. 204) and their suspected neurotransmitters are identified. The functional relations between the afferent projections to neostriatum and the intrinsic elements of neostriatum are described. A division of the neostriatal efferents into two functional cell systems is conceived, in which one efferent system, the Spiny I cell matrix, is thought to be represented by a lateral inhibitory network comprised of the common Spiny I neurons which inhibit their targets, while another is termed the Spiny II cell cluster and consists of the far less numerous excitatory efferents of neostriatum (the Spiny II cells) and is represented by clusters of neurons, the members of each cluster consisting of one excitatory efferent neuron and three interneurons. The implications of this view for neostriatal input--output relations are discussed, and the theory is developed by reference to a variety of converging lines of empirical evidence, and is used to interpret the effects of various pharmacologic strategies which have been employed to achieve symptom management in disorders of voluntary movement. In the course of this review, there emerges an integrative theory of the principles governing the neostriatal control of voluntary movement.

Afferent Pathways↗
PubMed1983

Three-dimensional structure of dendritic spines in the rat neostriatum.

Dendritic spines of rat neostriatal neurons were examined by light microscopy and high voltage stereo electron microscopy (HVEM) following selective staining by intracellular microinjection of horseradish peroxidase. Conventionally prepared material also was used for quantitative analysis of dendritic spines from serial thin sections of neostriatum. Stereo electron microscopy of semithin sections from rat neostriatum fixed using a protocol designed to preserve cytoskeletal integrity was employed to examine the organization of the dendritic spine cytoplasm. Light microscopic and HVEM examination of spiny dendrites and quantitative analysis of serial thin sections from normal material revealed no distinct spine types but rather continuous and independent variation of spine head diameter, stalk diameter, and stalk length. Likewise, there was no systematic relationship between any of these spine dimensions and dendritic diameter. Spine head membrane surface area was directly related to the area of the synaptic junctional membrane of the spine head. In semithin sections, the cytoplasm of the spine contained membranous saccules of spine apparatus and a delicate cytoskeletal network composed of microfilaments and a set of finer and more variable cytoskeletal filaments. It is proposed that this cytoskeletal network together with the spine apparatus is responsible for the maintenance and alteration of spine shape and in this way controls the effectiveness of axospinous synapses.

Animals↗
PubMed1982

Dopaminergic terminal excitability following arrival of the nerve impulse: the influence of amphetamine and haloperidol.

Variations in the excitability of the axons and terminal fields of dopaminergic neurons of the substantia nigra were examined as a function of time following the nerve impulse in urethane-anesthetized, immobilized rats. Excitability was measured by determining the threshold, defined as the minimum current required to consistently activate dopaminergic neurons antidromically. Threshold currents were maximal immediately following the action potential and declined exponentially to a plateau. The interval during which threshold current declined, the phasic period, was significantly longer for stimulation of neostriatal terminal fields as contrasted to stimulation of axons along the medial forebrain bundle. A positive correlation was observed between antidromic response latency and the duration of this phasic period for both sites of stimulation, an observation consistent with the view that the site of initiation of the antidromic action potential is of smaller diameter in the neostriatum than in the medial forebrain bundle Amphetamine, which promotes dopamine release and/or re-uptake blockade, reduced dopaminergic terminal excitability in the neostriatum at all intervals examined. This effect increased at successively shorter intervals during the phasic portion of the excitability curve. Haloperidol, a dopamine antagonist, increased the excitability of dopaminergic terminal fields, an effect which was also more marked earlier in the phasic interval. Neither amphetamine nor haloperidol had a significant effect on the excitability of dopaminergic axons in the medial forebrain bundle. Variations in dopaminergic terminal excitability after impulse arrival, and the effects of amphetamine and haloperidol on this phenomenon suggest that terminal excitability is determined by events related to arrival of the nerve impulse including activation of presynaptic 'autoreceptors' by dopamine released from the synaptic ending.

Amphetamine↗
PubMed1982

Noradrenergic terminal excitability: effects of opioids.

The local infusion of morphine or D-Ala2, Met5-enkephalinamide into the frontal cortical terminal fields of noradrenergic neurons of the nucleus locus coeruleus resulted in a decrease in the excitability of the axon terminal regions to direct electrical stimulation. These effects were concentration dependent and could be blocked or partially reversed by the local infusion of naloxone. Some evidence was obtained for a differential antagonizing effect of naloxone upon the effects of morphine and D-Ala2, Met5-enkephalinamide. These results are discussed with respect to an effect of opioids on the polarization and/or ionic conductance of the terminal fields of locus coeruleus neurons, and to the possible regulation of neurotransmitter release by presynaptic opiate receptors.

Animals↗
PubMed1982

Changes in noradrenergic terminal excitability induced by amphetamine and their relation to impulse traffic.

The effects of amphetamine upon the terminal excitability of noradrenergic neurons of the nucleus locus coeruleus were studied in urethane anesthetized rats. Terminal excitability was measured by determining the stimulus currents necessary to evoke antidromic responses in locus coeruleus neurons from terminals in the frontal cortex. In most cases, terminal excitability was decreased following local infusion of amphetamine into the frontal cortex, while intravenous administration of the drug tended to increase terminal excitability. The decreased terminal excitability induced by local infusion of amphetamine appeared to be due to activation of alpha-adrenergic receptors located on the terminals of locus coeruleus neurons, since this effect mimics that of clonidine, a direct acting alpha-adrenergic agonist, and since the effect was abolished by pretreatment with alpha-methyl-p-tyrosine which disrupts the catecholamine liberating properties of amphetamine. Phentolamine, a direct acting alpha-adrenergic receptor antagonist was also found to block or reverse the effect of amphetamine. The changes in terminal excitability following intravenous injection of amphetamine appeared to be related to changes in the spontaneous activity of locus coeruleus neurons. A large decrease in spontaneous activity following intravenous administration of amphetamine was associated with increased terminal excitability, whereas when smaller changes in spontaneous activity occurred, terminal excitability was found to be decreased. These results are discussed with respect to the pharmacological properties of catecholaminergic neurons and the mechanisms of action of amphetamine.

Animals↗
PubMed1982

Subsensitivity of catecholaminergic neurons to direct acting agonists after single or repeated electroconvulsive shock.

Spontaneous firing rates and changes in firing rate in response to an intravenously administered dose of apomorphine were measured after various electroconvulsive shock (ECS) treatment regimens from dopaminergic cells of the substantia nigra in urethane-anesthetized rats. Similar measurements were obtained from noradrenergic neurons of the locus coeruleus before and after intravenous injection of clonidine. A significant decrement in the inhibition of spontaneous firing in response to intravenous administration of these agonists was observed following multiple or single ECS treatment in both substantia nigra and locus coeruleus cells. There was a consistent but nonsignificant tendency for cells in both areas of the brain from treated animals to display higher rates of spontaneous firing than their respective sham-shocked controls. Both the effects on base-line rates of spontaneous activity and on the depression of firing rate in response to drug administration were found to be independent of repeated treatment. A significant negative correlation was obtained between base-line firing rate and percentage depression to the autoreceptor agonist, but this correlation alone was insufficient to account for the observed differences in the drug response. These results are discussed with respect to possible mechanisms of action of electroconvulsive therapy in the treatment of depression.

Animals↗
PubMed1981

Neurophysiological consequences of presynaptic receptor activation: changes in noradrenergic terminal excitability.

Experiments were carried out to explore the view that activation of presynaptic receptors on the terminals of noradrenergic neurons is accompanied by alterations in their excitability to direct electrical stimulation. Antidromic action potentials evoked from frontal cortex of urethane anesthetized rats were recorded extracellularly from nucleus locus coeruleus. The threshold current necessary to evoke antidromic action potentials varied as a result of infusion of adrenergic agonists and antagonists into frontal cortex within 50 micrometer of the stimulating electrode. Local infusion of the alpha-adrenergic agonist clonidine produced a marked decrease in terminal excitability, while the alpha-antagonist phentolamine produced an increase in terminal excitability and was shown to reverse the effect of the agonist. Infusion of the beta-adrenergic agonist isoproterenol was without effect, although the beta-antagonist propranolol resulted in a decrease in terminal excitability. Infusions of potassium increased excitability of locus coeruleus terminals. Terminal excitability was seen to vary inversely with the rate of spontaneous or high frequency stimulation-induced firing of locus coeruleus neurons. From these observations, it may be inferred that activation or blockade of alpha-adrenergic presynaptic receptors results in changes in polarization and/or conductance of the noradrenergic synaptic endings. These results are discussed with respect to phenomena associated with the possible presynaptic regulation of neurotransmitter release.

Animals↗
PubMed1981

Spontaneous firing patterns of identified spiny neurons in the rat neostriatum.

Spontaneous firing patterns of 94 unidentified neurons and 34 identified spiny neurons were compared in the neostriatum of locally anesthetized immobilized rats. Intracellular and extracellular recordings were analyzed using first order interval histograms and autocorrelograms, and neurons were identified by their somatodendritic morphology after intracellular injection of horseradish peroxidase. All neostriatal neurons tended to fire in irregular phasic bursts of activity. Considerable variation in mean firing rate, burst duration, interburst interval and the occurrence and rate of firing between bursts was apparent in both groups of neurons. There was no apparent difference between spiny neurons and the sample of unidentified extracellularly recorded neurons along any of these firing pattern parameters. Intracellular recordings from identified spiny neurons revealed noisy irregular periods of maintained 5-20 mV membrane depolarizations which corresponded to the occurrence of bursts of firing in spontaneously active neurons. These depolarizations occurred in neostriatal neurons exhibiting no spontaneous activity but were of insufficient amplitude to trigger impulse activity.

Animals↗
PubMed1981

Dopamine receptor changes following destruction of the nigrostriatal pathway: lack of a relationship to rotational behavior.

Phenomena consistent with postsynaptic supersensitivity developed in the rat neostriatum following the destruction of dopaminergic afferent neurons. A gradual increase in the density of binding sites for [3H]spiperone occurred over a 2-3 week period. This increase was apparent only after the almost complete loss of dopamine-containing nerve terminals as measured by the depletion of endogenous dopamine. The properties of the receptor labeled by [3H]spiperone were not altered by denervation. Elimination of dopamine-containing nerve endings in the neostriatum was accompanied by the gradual development of an increase in dopamine-sensitive adenylate cyclase activity in homogenates of the caudate ipsilateral to the lesion as compared to the contralateral side. The administration of apomorphine led to pronounced circling behavior. This effect occurred rapidly and was maximal within 3 days following destruction of dopaminergic neurons. The increase in the density of dopamine receptors and in a receptor-mediated function may partially account for the development of enhanced electrophysiological responses to dopamine agonists in the neostriatum. However, the results do not explain the drug-induced rotational behavior which develops after destruction of the dopamine-containing nigrostriatal pathway. This behavioral phenomenon clearly preceded the appearance of receptor alterations in the corpus striatum.

Adenylyl Cyclases↗
PubMed1980

Fine structure and synaptic connections of the common spiny neuron of the rat neostriatum: a study employing intracellular inject of horseradish peroxidase.

Medium-sized spiny neurons of the neostriatum, identified by intracellular injection of horseradish peroxidase, were examined at both light and electron microscopic levels. These neurons were characterized by their heavy investment of dentritic spines, beginning about 20 micron from the soma and continuing to the tips of the dendrites. Their axons arose from the soma or from a large dendritic trunk very near the soma, and tapered rapidly to form a main axonal branch from which arose several smaller initial collaterals. These arborized extensively throughout an area of about the same size as, and highly overlapping with, the dendritic field of the cell, while the main axon could be followed for distances of up to 1 mm in the direction of the globus pallidus. Three major synaptic types were seen in contact with spiny neurons. Boutons containing small round synaptic vesicles formed synapses exclusively with spiny regions of the dendrites, and most of these were axo-spinous. Small, very pleomorphic synaptic vesicles characterized a second bouton type of unknown origin, which made contacts with somata, initial segments, and dendrites, but not dendritic spines. Boutons containing large pleomorphic synaptic vesicles had the most widespread distribution, contacting all regions including dendritic spines. Spines receiving these contacts also were postsynaptic to boutons containing small round vesicles. Axon collaterals of spiny cells formed synapses with large pleomorphic vesicles and made synapses with somata, initial segments of axons, dendrites, and dendritic spines of striatal neurons, including other spiny cells.

Animals↗
PubMed1980

Fine structure of rat locus coeruleus.

Locus coeruleus of the rat was studied in material prepared by aldehyde-osmium fixation. Cell bodies of locus coeruleus neurons possess large nuclei with a prominent nucleolus, a homogeneous karyoplasm of moderate density, and occasional indentations of the nuclear membrane. The cytoplasm is rich in organelles, including an extensive network of endoplasmic reticulum which forms well organized Nissl bodies. The highly developed Golgi apparatus surrounds the nucleus and extends into large dendritic trunks. In coronal section, cell bodies appear elongated along an approximate dorso-ventral axis, and most dendrites as well as axons appear in cross-section. In parasagittal sections the cells are very elongate, with dendrites and axons in the neuropil mostly cut longitudinally. Thus, locus coeruleus neurons possess disc-shaped dendritic fields parallel to the anterior-posterior axis of the brainstem, with predominantly longitudinal axo-dendritic synaptic configurations. Presynaptic profiles in locus coeruleus neuropil were classified according to the characteristics of their vesicle populations and other features. The most frequently encountered synaptic ending was characterized by small, round, densely packed synaptic vesicles, and comprised approximately 41% of the total sample of 775 synapses. Another group having large, rounded synaptic vesicles, which could be traced in a number of instances to large myelinated axons, accounted for 20% of the sample. Synaptic endings having large, flattened vesicles were also numerous, comprising 23% of the total. Another category of presynaptic endings was identified as those possessing numerous, small, flattened vesicles and comprising about 11% of the sample. Presynaptic endings having many vesicles of mixed sizes accounted for 2% of the total, and another group of the same proportion having small, rounded synaptic vesicles but also an unusually large number of larger, dense-cored vesicles was also present. Two other categories of synaptic endings were encountered, each comprising less than 1% of the total. One of these was derived from small, unmyelinated axons and contained clusters of pleomorphic synaptic vesicles. The other consisted of dendro-dendritic synapses between locus coeruleus neurons and also displayed small clusters of pleomorphic synaptic vesicles near the zone of synaptic apposition. Quantitative analysis revealed that most afferents to the nucleus synapse onto dendrites ranging between 0.5 and 2.5 micrometers in diameter and onto spine-like appendages derived from somata and dendrites. There were no significant differences between different categories of afferent terminals and their spatial distribution onto various postsynaptic targets of locus coeruleus neurons.

Animals↗
PubMed1980

Monoaminergic presynaptic axons and dendrites in rat locus coeruleus seen in reconstructions of serial sections.

Locus coeruleus was studied in rats pretreated with intraventricularly administered 5-hydroxydopamine 1/2 to 3 hours prior to conventional aldehydeosmium fixation. Presynaptic profiles in locus coeruleus neuropil were classified according to the characteristics of their vesicle populations and other features, as in our previous report. Similar categories of endings were observed, and the sites of postsynaptic innervation were identical to those described previously, that is, a majority of synapses were made with dendrites between 0.5 and 2.5 micrometers in cross-sectional diameter, a significant proportion was seen ending onto somatic and dendritic spines, with a relative paucity of synapses made with spine-free membrane of somata and large dendritic trunks. There were no significant differences between different morphological categories of afferent terminals and their spatial distribution onto various postsynaptic targets on locus coeruleus neurons. In addition to various membrane-bound compartments of the cytoplasm, three categories of synaptic endings were labelled by the synaptic marker, while all others were unlabelled. One of these was identified previously as containing small, rounded synaptic vesicles and an unusually large number of large, dense core vesicles. The synaptic vesicles were lightly labelled with scattered, small, eccentrically placed opaque cores inside the synaptic vesicles, apparently randomly distributed throughout the terminal. This terminal is thought to be serotonergic. A second category of labelled synapse has been previously identified as that derived from small, unmyelinated axons having clusters of pleomorphic synaptic vesicles in which the vesicles are heavily labelled by 5-hydroxydopamine. These are believed to represent catecholaminergic synaptic endings derived from recurrent collaterals as well as extrinsic catecholaminergic innervation of locus coeruleus. A final category of heavily labelled profile was identified as presynaptic dendrites, which, along with recurrent catecholaminergic axon collaterals, probably play an important part in the intrinsic regulation of nucleus locus coeruleus. When 59 labelled synapses were examined in adjacent serial sections, every vesicle-containing profile was associated with a synaptic contact having characteristic membrane specializations. A similar result was obtained when 132 other unlabelled terminals of different categories were examined in serial sections.

Animals↗
PubMed1980

The effect of long-term amphetamine administration on the activity of dopaminergic neurons of the substantia nigra.

Spontaneously active neurons from the pars compacta region of the substantia nigra were studied in chloral hydrate anesthetized, immobilized rats which had been pretreated with daily intraperitoneal saline or D-amphetamine injections according to several schedules. The spontaneous firing rates of these neurons were not altered by any of the pretreatment regimens. In addition, the intravenous dose of D-amphetamine sulfate which was required to reduce the spontaneous firing rate of these cells by at least 50% (threshold dose) was not modified by amphetamine pretreatment. There was a significant positive linear correlation between the threshold dose and the initial spontaneous firing rate of the neurons from animals pretreated with multiple saline injections, but not from those receiving long-term D-amphetamine. These results demonstrate that there are no alterations in the sensitivity of dopaminergic neurons to amphetamine under conditions known to produce the enhanced effects of the drug on motor behaviors which develop during multiple injections.

Animals↗
PubMed1980

Synaptic endings and their postsynaptic targets in neostriatum: synaptic specializations revealed from analysis of serial sections.

Neostriatal tissue from rat brain was examined in ribbons of serial sections, using tissue from subjects in which the synaptic marker 5-hydroxydopamine had been injected into the lateral ventricle. A total of 440 synaptic terminals, identified by the presence of a population of vesicles, was studied, including those labeled by 5-hydroxydopamine and all those unlabeled in the surrounding neuropil. Three categories of synaptic profiles innervating neostriatal dendrites could be discerned. One category contained small rounded or slightly pleomorphic vesicles and consisted of a sample of 375 endings, 53 of which exhibited light to heavy label inside the synaptic vesicles. All of these, labeled and unlabeled, showed evidence of membrane specializations and other conventional criteria of synaptic contact, mostly in the form of asymmetric synaptic contacts with the heads of dendritic spines. A second category of 40 terminals, 3 of which were lightly labeled, contained large rounded or slightly pleomorphic vesicles and made predominantly symmetric contacts with the shafts of dendritic spines or spine-free portions of dendritic membrane. None of these synaptic endings appeared to lack synaptic contact with postsynaptic targets in the neostriatum. A third category of 25 terminals, 3 of which were labeled, contained small flattened vesicles, and these endings also invariably made synaptic contact, mostly onto spine-free dendritic membrane, and were characterized by symmetric membrane thickenings at the point of apposition. Our evidence supports the view that dopaminergic and other synaptic terminals in the rat caudate-putamen make synaptic contact with postsynaptic targets in the neostriatum and, at least in the adult, do not exist in appreciable numbers in the form of terminals that are not apposed to membranes of postsynaptic targets in the neostriatum.

Animals↗
PubMed1979

A simple and rapid section embedding technique for sequential light and electron microscopic examination of individually stained central neurons.

A method for section embedding of central nervous tissue, and its application to light and electron microscopic examination of neurons stained by intracellular injection of horseradish peroxidase, is described. After primary fixation in aldehydes, thick (10--80 micrometer) sections are cut on a Vibratome. They are then treated for the histochemical demonstration of peroxidase, postfixed in osmium tetroxide, dehydrated and infiltrated with Spurr's low viscosity resin. Infiltrated sections are embedded between glass slides and coverslips coated with a transparent layer of teflon and polymerized. The resulting mount allows protracted storage and high resolution light microscopic examination of sections. When desired, the glass components can be removed and the specimen cemented to a blank block for thin sectioning and electron microscopic examination.

Animals↗