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P M Groves

Publications and source records attributed to P M Groves.

At least 37 records · Page 2Linked to original sources
PubMed1991

Terminal excitability of the corticostriatal pathway. II. Regulation by glutamate receptor stimulation.

The influence of impulse activity and glutamate receptor stimulation on the electrical excitability of the corticostriatal terminal field was explored. Antidromic responses were recorded from prefrontal cortical neurons the electrical stimulation of their terminal field in the contralateral striatum. Terminal excitability was assessed by determining the percentage of subthreshold current stimulus presentations eliciting an antidromic response. Terminal excitability was found to be positively correlated with variations in spontaneous firing rate: increases and decreases in firing rate were accompanied by corresponding changes in the percentage of antidromic responses elicited by a subthreshold stimulus. Drugs were applied to the striatal stimulation site in a volume of 312 nl delivered over 5 min. Striatal administration of either the competitive NMDA antagonist D-alpha-aminoadipate (DAA) or D-2-amino-7-phosphonoheptanoate (AP-7) or the competitive non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) blocked the correlation between excitability and firing rate. Further examination revealed that the terminal field was rendered more excitable for a period of 20-80 ms following the arrival of an action potential. This post-impulse facilitation of terminal excitability was attenuated after local application of AP-7 (10 microM) or CNQX (20 microM). At half these doses, AP-7 or CNQX produced a non-significant effect, however when administered simultaneously a significant attenuation was observed. The participation of interneurons in these excitability effects was ruled out since they were still seen following kainic acid lesions. We propose that this impulse-dependent enhancement in terminal excitability results from the release of glutamate induced by the action potential in the terminal field and the subsequent stimulation of glutamate autoreceptors on the terminals.

2-Amino-5-phosphonovalerate↗
PubMed1991

A GABA immunocytochemical study of rat motor thalamus: light and electron microscopic observations.

A light and electron microscopic study of GABA-immunoreactive neurons and profiles in the ventroanterior-ventrolateral and ventromedial nuclei of rat dorsal thalamus was conducted using antiserum raised against GABA. Less than 1% of the neurons in these motor-related nuclei exhibited GABA immunoreactivity, confirming previous reports that these nuclei are largely devoid of interneurons. Immunoreactive neurons in the ventral anterior-ventral lateral complex and ventromedial nucleus were bipolar or multipolar in shape, and tended to be smaller than non-immunoreactive neurons. GABA immunoreactivity in the neuropil consisted of labeled axon terminals and myelinated and unmyelinated axons, and was lower in the ventral anterior-ventral lateral complex and ventromedial nucleus than in neighboring thalamic nuclei. The density of neuropil immunolabeling was slightly higher in ventral anterior-ventral lateral complex than in ventromedial nucleus. GABA-immunoreactive axon terminals, collectively termed MP boutons for their medium size and pleomorphic vesicles (and corresponding to "F" profiles of some previous studies of thalamic ultrastructure), formed symmetric synapses and puncta adhaerentia contacts predominantly with large and medium-diameter (i.e. proximal) non-immunoreactive dendrites. Approximately 12 and 18% of boutons in the ventral anterior-ventral lateral complex and ventromedial nucleus, respectively, were GABA-immunopositive. Many of these immunoreactive profiles probably arose from GABAergic neurons in the thalamic reticular nucleus, substantia nigra pars reticulata and entopeduncular nucleus. Two types of non-immunoreactive axon terminals were distinguished based on differences in morphology and synaptic termination sites. Boutons with small ovoid profiles and round vesicles that formed prominent asymmetric synapses onto small-diameter dendrites were observed. Mitochondria were rarely observed within these boutons, which arose from thin unmyelinated axons. These boutons composed approximately 82 and 74% of boutons in the ventral anterior-ventral lateral complex and ventromedial nucleus, respectively, and were considered to arise predominantly from neurons in the cerebral cortex. In contrast, boutons with large terminals that contained round or plemorphic vesicles and formed multiple asymmetric synapses predominantly with large-diameter dendrites were also observed. Puncta adhaerentia contacts were also common. Mitochondria were numerous within large boutons with round vesicles, which arose from myelinated axons. Many of the large boutons were likely to have originated from neurons in the cerebellar nuclei. Approximately 6% of the boutons in the ventral anterior-ventral lateral complex and 8% in ventromedial nucleus were of the large type.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Electrophysiological characteristics of cells within mesencephalon suspension grafts.

Both spontaneous and evoked extracellular electrophysiological activity of neurons within fetal mesencephalon suspension grafts to the dopamine-depleted striatum of rats were examined. In some cases, extracellular recording was combined with intracellular labeling to identify recorded neurons. Grafted rats displaying a complete cessation of ipsilateral rotations following amphetamine administration were examined at post-implantation time intervals of two, four, five, eight and nine months. Four separate classes of neurons were distinguished within the transplanted striatum based on electrophysiological properties. The first of these groups, the type I cells, appeared to be non-grafted striatal neurons. When spontaneously active, these striatal-like cells fired bursts of action potentials separated by periods of decreased activity. Evoked responses in these cells were characteristic of striatal cells. Type I cells which were intracellularly labeled were found outside the grafts and displayed the characteristic morphology of the medium spiny neuron of the neostriatum. The other three cell classes displayed electrophysiological properties similar to neurons recorded in situ within the reticular formation, substantia nigra pars compacta and substantia nigra pars reticulata. Neurons from these three groups which were labeled with an intracellular marker were found to lie within the suspension grafts. The spontaneous activity of the pars compacta dopaminergic-like neurons was predominantly irregular, with some cells also firing in a regular or pacemaker-like pattern. Infrequently, irregular firing dopaminergic-like neurons displayed episodes of doublet bursting. Many of the grafted neurons responded to electrical stimulation of prefrontal cortex and striatum, indicating that the graft was receiving functional inputs from host neurons. Comparison of the firing rate and pattern of grafted neurons to in situ mesencephalic neurons as a function of time following grafting suggested that the grafted neurons and/or the neuronal circuitry is slowly developing within the host environment. A prolonged time-course for the maturation of the graft may be reflected in the time required to achieve improvements in some behavioral deficits following transplantation. However, the relatively rapid recovery of drug-induced rotational asymmetry following grafting suggests that this form of recovery may not require mature functioning of the grafted neurons.

Animals↗
PubMed1991

Modulation of dopaminergic terminal excitability by D1 selective agents: further characterization.

We have previously shown that stimulation of striatal D1 receptors affects dopaminergic nigrostriatal terminal excitability, which is thought to be an index of biophysical events resulting from the activation of receptors on the presynaptic membrane. The experiments presented here further examine the locus and bases of these D1 effects in the rat. We now report that striatal administration of the D1 receptor selective antagonist R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazapine+ ++-7-ol-HCl (SCH 23390) produces a paradoxical agonist-like decrease in dopaminergic terminal excitability. This effect is blocked by pretreatment with the dopamine synthesis inhibitor, alpha-methyl-paratyrosine, suggesting that the action of SCH 23390 is dependent upon endogenous dopamine. Further, haloperidol pretreatment also prevents the SCH 23390-induced decrease in terminal excitability, confirming that dopamine, acting through a dopamine receptor, is responsible for this agonist-like action. Striatal application of the active R-(+) enantiomer of the dopaminergic D1-selective agonist 1-phenyl-2,3,4,5-tetrahydrol-(1H)-3-benzazepine-7,8-diol-HCl (R-SKF 38393) decreases terminal excitability in the alpha-methyl-paratyrosine pretreated animal, indicating that dopamine is not required for the agonist action. In an effort to ascertain the presynaptic or postsynaptic location of these actions, an extensive destruction of postsynaptic neurons in the neostriatum was produced by local administration of the neurotoxin, kainic acid. It was observed that the neurotoxin-induced neostriatal neuronal loss did not disrupt the action of R-SKF 38393 nor its reversal by SCH 23390.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Histological and ultrastructural evidence that D-amphetamine causes degeneration in neostriatum and frontal cortex of rats.

D-Amphetamine sulfate, continuously administered for 3 days subcutaneously via an implanted minipump, induced neural degeneration in Long-Evans and Sprague-Dawley rats at doses between 20 and 60 mg/kg/day. Using Fink-Heimer silver staining, axonal degeneration was detected in the neostriatum and the dorsal agranular insular cortex and degenerating pyramidal cells were observed in portions of the somatosensory neocortex in both strains. In contrast, dense axonal degeneration largely confined to layers 2 and 3 of frontal motor areas (Fr1, Fr2 and Fr3 of Zilles36) with occasional degenerating cells was seen reliably in Long-Evans rats but rarely in Sprague-Dawley rats. In the electron microscope, cortical degeneration consisted mainly of disrupted cell bodies and dark processes, including axons making asymmetric synapses. Damage in all cortical areas represents damage to non-monoamine neurons and processes since tyrosine hydroxylase and serotonin immunolabeling were normal. In contrast, the damage in neostriatum probably includes damage to dopamine axonal terminals since tyrosine hydroxylase immunolabeling was patchy with many swollen and distorted labeled axons. Serotonin and Leu-enkephalin labeling were normal. Electron microscopy confirmed that the neostriatum contained many tyrosine hydroxylase-labeled axons that were swollen and disrupted, although other labeled processes made normal symmetric synapses onto spines and dendrites. Additional degeneration found only in amphetamine-treated rats included many dark, shrunken profiles. Some of these appeared to be astrocytic processes and a few were myelinated axons, suggesting that some non-monoamine, possibly cortical afferents, are also degenerating in the neostriatum. Since similar degrees of behavioral activation, weight loss and lethality were seen in both strains, a genetic predisposition constrain amphetamine-induced motor cortex damage but not neostriatal damage.

Animals↗
PubMed1990

Effects of long-term administration of haloperidol on electrophysiologic properties of rat mesencephalic neurons.

Haloperidol (1.5-1.7 mg/kg/day) was administered to rats via their drinking water for periods of either 4 weeks or 13 to 14 months, after which the animals were withdrawn from the neuroleptic for 1 or 2 weeks, respectively. Rats given haloperidol for 13 to 14 months exhibited significantly more perioral dyskinesias than controls. Single-unit extracellular recordings were obtained from the substantia nigra and ventral tegmental area in subjects under urethane anesthesia. After 1 month and after 1 year of treatment, a significant decrease in the mean firing rate of substantia nigra pars reticulata neurons was found. Subtle changes in the response of pars reticulata neurons to striatal stimulation were seen after extended haloperidol intake. No consistent effects of haloperidol administration for 4 weeks or 13 to 14 months were found for either the number of spontaneously active dopamine neurons or their firing rates. Histopathologic assessment of tissue from dorsomedial, dorsolateral and ventrolateral sectors of the striatum revealed no significant effect of long-term haloperidol treatment on neuronal cell counts. The results are discussed with reference to neuroleptic-induced tardive dyskinesias.

Animals↗
PubMed1989

Quantitative Golgi study of anatomically identified subdivisions of motor thalamus in the rat.

A Golgi study of neurons in the ventroanterior-ventrolateral complex (VAL) and ventromedial (VM) nucleus in the dorsal thalamus of rats was performed. To facilitate the delineation of subdivisions of these nuclei, some animals received injections of horseradish peroxidase (HRP) into the afferent and efferent fields of VAL and VM, and alternate sections were processed for the histochemical detection of HRP. As an adjunct to subjective observations, a multivariate statistical analysis of morphometric variables was performed to provide an objective assessment of neuronal morphology. All Golgi-stained neurons in VAL and VM were tentatively identified as projection neurons; no cells with morphological features commonly ascribed to thalamic interneurons were impregnated. Four classes of morphologically distinct neurons were identified in VAL. Type 1 neurons, the most commonly impregnated cell, were found throughout the extent of VAL and resembled "tufted" or "multipolar bush" neurons described previously in many thalamic nuclei. The remaining three neuronal types differed in a number of morphometric parameters and were differentially distributed throughout VAL. Type 2 neurons, distinguished in part by dendritic spine morphology and elongated bipolar dendritic fields, were found only in the rostral sector of the dorsal division of VAL (VALD). Type 3 neurons, characterized by a large and evenly distributed dendritic field, were situated in rostral VAL (all subdivisions). Type 4 neurons had small soma and dendritic dimensions and were located in the ventromedial aspect of the ventral division of VAL (VALV) adjacent to VM. In contrast, the vast majority of neurons in VM were considered to be a single morphological class (similar in form to type 4 neurons in VAL), although a rarely impregnated second type of neuron was also observed. The apparent scarcity of interneurons in VAL and VM is consistent with previous evidence that the synaptic organization of motor thalamus in the rat is markedly different from that of higher-order mammals. Speculation about the functional attributes of the neuronal types in VAL and VM is necessarily restricted to considerations of afferent and efferent relations, since "motor modality" functions of neurons in these nuclei have yet to be elucidated.

Animals↗
PubMed1989

Dopamine D1 heteroreceptors on striatonigral axons are not stimulated by endogeneous dopamine either tonically or after amphetamine: evidence from terminal excitability.

The role of dopamine D1 heteroreceptors located on the axon terminals of striatonigral neurons was investigated. Local infusion of the direct acting, specific dopamine D1 agonist, R-SKF 38393, into the substantia nigra terminal field of antidromically identified neostriatal projection neurons decreased the electrical excitability of these axons. This effect was dose-dependent and could be partially reversed by subsequent infusion of the specific D1 antagonist, R-SCH 23390. In contrast, excitability was not affected by the systemic administration of SCH-23390 (0.3 and 0.6 mg/kg, iv), or the non-specific antagonist haloperidol (0.2 mg/kg, iv). Since activation of the D1 heterorecptors by R-SKF 38393 decreased excitability, the inability of these antagonists to modify excitability indicates that endogenous dopamine does not tonically activate these receptors. Systemic administration of the indirect acting agonist, amphetamine (1.0 and 5.0 mg/kg, iv) also failed to change terminal excitability suggesting that, even when unnaturally high levels of dopamine are released in the substantia nigra, endogenous dopamine does not affect neostriatal axons terminating in the substantia nigra. Thus it is unlikely that endogeneous dopamine modulates neostriatal control of the substantia nigra through these presynaptic terminal D1 heteroreceptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

A mechanism for the involvement of colocalized neuropeptides in the actions of antipsychotic drugs.

Evidence has accumulated to implicate neuropeptides localized within midbrain dopamine neurons (cholecystokinin, neurotensin, acetylcholinesterase) in synaptic transmission, mental disease, and pharmacotherapy. We suggest a means by which antipsychotic drugs alter the dynamics between dopamine and colocalized peptides: the intrinsic ability of these agents to stimulate dopamine neuronal activity while blocking dopamine receptors modulates the ratio of catecholaminergic to peptidergic transmission within the mesotelencephalic system. Imbalances of peptide and dopamine cotransmission and their modulation by neuroleptics may be relevant to the pathogenesis and pharmacotherapy of schizophrenia.

Animals↗
PubMed1989

Modulation of dopaminergic terminal excitability by D1 selective agents.

The effect of the active R (+) enantiomer of the dopaminergic selective D1 agonist 1-Phenyl-2,3,4,5-tetrahydrol-(1H)-3-benzazepine-7,8-diol HCL (R-SKF 38393) was examined on the excitability of antidromically identified nigro-striatal dopaminergic neurons. Striatal infusions of R-SKF 38393 produced a decrease in terminal excitability, which was reversed by subsequent infusion of the Dopaminergic D1 selective antagonist R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-o l-HCL (SCH 23390). The actions of these D1 specific agents are localized to the terminal fields of the dopaminergic neurons and are not nonspecific effects on the axonal membrane since application along the axons of these cells in the medial forebrain bundle produced no change (R-SKF 38393) or only a slight decrease (SCH 23390) in excitability. The results suggest that the terminal excitability of antidromically identified nigro-striatal dopaminergic neurons can be modified with specific Dopamine D1 receptor agents via a receptor mediated mechanism. Previous studies from this laboratory have demonstrated that the electrical excitability of nigro-striatal dopaminergic terminals is reduced by the dopaminomimetics apomorphine and amphetamine and is increased by the dopamine antagonists haloperidol, fluphenazine and sulpiride (Groves, Fenster, Tepper, Nakamura, and Young 1981; Tepper, Nakamura, Young and Groves 1984). Since, with the exception of sulpiride, these compounds affect both the D1 and D2 subclasses of dopamine receptors, it can not be concluded from these reports, which, if only one, of these receptors mediates the effect on terminal excitability.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Mesocortical dopaminergic neurons. 1. Electrophysiological properties and evidence for soma-dendritic autoreceptors.

Mesencephalic dopaminergic neurons were electrophysiologically identified by a variety of criteria, including antidromic activation from prefrontal or cingulate cortex, neostriatum, or nucleus accumbens in urethane-anesthetized rats. The mean firing rate of 98 mesocortical dopaminergic neurons was 2.9 +/- 0.3 spikes/sec and did not differ from the mean firing rate found for nigrostriatal or nucleus accumbens dopaminergic neurons. Spontaneously active mesocortical dopaminergic neurons were inhibited by intravenous administration of either apomorphine (6 micrograms/kg) or amphetamine (0.25 mg/kg). Whereas most antidromic responses of nigrostriatal and mesoaccumbens neurons consisted of the initial segment spike only, cortically-elicited antidromic responses typically consisted of a full initial segment-soma-dendritic spike. These findings are discussed with regard to the presence of soma-dendritic autoreceptors on mesocortical dopaminergic neurons.

Action Potentials↗
PubMed1989

Mesocortical dopaminergic neurons. 2. Electrophysiological consequences of terminal autoreceptor activation.

Measurement of drug- and stimulation-induced changes in the electrical excitability of dopaminergic terminals was employed to assess the effects of stimulation of dopamine terminal autoreceptors in the prefrontal cortex in urethane-anesthetized rats. Systemic or local administration of amphetamine decreased, whereas systemic administration of haloperidol increased the excitability of prefrontal cortical dopaminergic terminals of ventral tegmental area dopaminergic neurons. Mesoprefrontal dopaminergic terminal excitability was also responsive to spontaneous and stimulation-induced alterations in the rate of impulses reaching the terminal fields. These results are comparable to those previously reported for nigrostriatal and mesoaccumbens dopaminergic neurons, and are discussed with regard to the operational characteristics of autoinhibition in the mesocortical dopaminergic system.

Action Potentials↗
PubMed1989

Antidromically identified striatonigral projection neurons in the chronically implanted behaving rat: relations of cell firing to amphetamine-induced behaviors.

The effects of systematically administered amphetamine (0.25-5.0 mg/kg, sc) on neostriatal neurons recorded in chronically implanted behaving rats were studied. Projection neurons, identified by antidromic activation from the substantia nigra, fired very infrequently during most predrug behaviors (e.g., median rate, 0.02 spikes per second during locomotion; 17 of 18 fired less than 1 spike per second during all rated behaviors). Nonantidromic cells also tended to fire slowly (median rate, 0.02 spikes per second during locomotion; 20 of 24 cells fired less than 1 spike per second). Cells of both type showed up to 10-fold variations in firing rate across behaviors. For most neurons, amphetamine caused a reduction in the firing rate during related pre- and postdrug behaviors. For instance, the firing rate of 28 of 42 neurons was reduced during the initial amphetamine-induced locomotion as compared with the rate during predrug locomotion. Moreover, with the higher doses of amphetamine, there was a further reduction in firing rate corresponding to the transition from locomotion to stereotypies. In contrast to previous studies, which suggest that amphetamine generally increases neostriatal firing rate in behaving animals, these results suggest that amphetamine inhibits the numerous slowly firing neostriatal neurons, many of which were identified as projection neurons. Thus amphetamine alters the magnitude and pattern of neostriatal control of its neural targets.

Action Potentials↗
PubMed1988

Burst firing induced in midbrain dopamine neurons by stimulation of the medial prefrontal and anterior cingulate cortices.

Extracellular recordings were obtained from mesencephalic dopamine neurons in urethane-anesthetized rats. A population of neurons responded to electrical stimulation of the frontal cortex with bursts of action potentials. These bursts resembled those that occur spontaneously in midbrain dopamine neurons with regard to length, interspike interval and post-burst inhibition. This is the first afferent input known to elicit bursting in dopamine neurons.

Action Potentials↗
PubMed1988

Cocaine, in contrast to D-amphetamine, does not cause axonal terminal degeneration in neostriatum and agranular frontal cortex of Long-Evans rats.

Continuous three day administration via implanted minipumps of cocaine hydrochloride (50-450 mg/kg/day, sc and 100-250 mg/kg/day, iv) did not produce axonal degeneration in frontal agranular cortex or neostriatum that was detectable by Fink-Heimer silver staining or tyrosine hydroxylase immunolabeling. This is in contrast to the extensive axonal degeneration detectable in these regions following d-amphetamine sulfate (10-60 mg/kg/day) administered following an identical protocol. Doses of cocaine and amphetamine were equated using three measures: 1) weight loss, 2) lethality and 3) behavioral activation. Thus, cocaine resembles other catecholamine reuptake blockers and does not cause the neurodegenerative changes characteristic of other abused drugs that interact with the brain's dopamine systems.

Animals↗