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P M Groves

Publications and source records attributed to P M Groves.

At least 19 recordsLinked to original sources
PubMed1992

Ultrastructural examination of enkephalin and substance P input to cholinergic neurons within the rat neostriatum.

Enkephalin and substance P-containing inputs to cholinergic perikarya were examined in the rat neostriatum using an ultrastructural immunocytochemical double-labeling protocol. Sections of rat neostriatum were double-labeled for either choline acetyltransferase (ChAT) and substance P or ChAT and enkephalin using silver intensified colloidal gold and peroxidase as labels. Regions containing both ChAT-positive neurons and peroxidase reaction product were identified in the light microscope prior to sectioning for electron microscopy. Substance P-containing terminals which contained round synaptic vesicles and made symmetrical synaptic contacts were commonly observed in the neostriatum. Substance P synapses onto ChAT-positive perikarya and dendrites were frequently observed: up to 5 synaptic contacts were observed onto a ChAT-positive dendrite. Enkephalin labeling was also seen in a population of axon terminals containing round synaptic vesicles and exhibiting symmetrical synaptic specializations. In contrast to substance P-containing terminals, relatively few synaptic contacts were observed onto ChAT-positive labeled perikarya and dendrites although enkephalin-labeled terminals were seen in frequent contact with perikarya and dendrites of unlabeled spiny neurons. Since enkephalin and substance P are contained within different populations of striatal spiny neurons, the results of the present study suggest that these two types of neurons differ in their intrinsic striatal connections.

Acetylcholine↗
PubMed1992

Presynaptic long-term changes in excitability of the corticostriatal pathway.

We employed measurements of striatal terminal excitability to monitor the presynaptic effects of tetanic stimulation of corticostriatal fibers. Cortical tetanic stimulation (CTS) initiated a long-lasting decrease in terminal excitability. With higher current CTS, a transient increase in excitability preceded the decrease. However, a long-term increase was induced (1) by a second tetanus applied during the brief elevation in excitability initiated by a previous CTS or (2) when dopamine and GABA transmission were disrupted. A long-term increase also occurred following tetanic stimulation of the striatal terminal field (STS). The direction of the long-lasting change in excitability may depend on the level of polarization of the membrane. These presynaptic mechanisms could be important for the long-term selective modification of striatal synaptic transmission.

Animals↗
PubMed1992

Effects of frequency and pattern of medial forebrain bundle stimulation on caudate dialysate dopamine and serotonin.

In vivo microdialysis was employed to detect changes in extracellular dopamine and serotonin in the rat caudate in response to electrical stimulation of the medial forebrain bundle. Extracellular dopamine concentrations increased linearly as a function of the frequency (4-33 Hz) of evenly spaced stimuli in both the presence and absence of cocaine added to the dialysate. Because dopamine neurons are known to fire in single-spike and burst patterns, stimulation pulses were also delivered in a bursting pattern. The response of extracellular dopamine was augmented in both the presence and absence of cocaine when the same number of stimuli were delivered in bursts as compared to an evenly spaced pattern. Serotonin, which was only assessed in the presence of cocaine, similarly increased linearly with frequency, but, in contrast to the dopamine response, levels of serotonin were not augmented by stimuli presented in bursts. These results suggest that microdialysis can be used to detect physiological changes in synaptic transmitter concentrations.

Animals↗
PubMed1991

Terminal excitability of the corticostriatal pathway. I. Regulation by dopamine receptor stimulation.

Glutamatergic cortical and dopaminergic nigral afferents converge onto neurons of the neostriatum forming synapses in close proximity. Studies, mainly using pharmacological methods, suggest presynaptic interactions between these afferents. The influence of dopaminergic transmission on the cortical terminal fields in the striatum was assessed electrophysiologically using the terminal excitability method. Antidromic action potentials recorded from neurons in the prefrontal cortex were elicited by bipolar electrical stimulation (250 microns wire, 0.5 mm tip separation) of the cortical terminal field in the contralateral dorsomedial neostriatum. Threshold excitability was defined as the minimum current sufficient to elicit 95-100% antidromic response on non-collision trials. Under control conditions, the mean threshold current was 1.7 +/- 0.2 mA. Drugs were applied in a volume of 312 nl delivered over 5 min to the striatal stimulation site. Following local striatal administration of amphetamine (10 microM) or electrical stimulation of the nigrostriatal pathway (1-2 pulses, 1.5 mA/0.5 ms/1 Hz) an increase in striatal stimulating current was required in order to reinstate threshold levels of antidromic response. This decrease in the excitability of corticostriatal afferents could be reversed by local infusion of haloperidol (1 microM) or L-sulpiride (10 nM) and did not occur following depletion of dopamine stores with alpha-methylparatyrosine and reserpine. The possible participation of postsynaptic dopamine receptor stimulation was ruled out as these effects were still seen in animals with kainic acid induced lesions of the striatum. In addition, terminal excitability was not modified by the muscarinic agonist carbachol (10 microM). Striatal administration of apomorphine (10 microM) decreased terminal excitability similar to amphetamine. The specific D-2 agonist, quinpirole (10-20 microM) did not affect excitability. These results indicate that manipulations which have been shown to increase the release of endogenous dopamine decrease the excitability of prefrontal corticostriatal afferents by stimulation of presynaptic dopamine receptors which are insensitive to low doses of quinpirole but sensitive to L-sulpiride and apomorphine. The mechanisms underlying dopamine-induced changes in terminal excitability are likely to be similar to those which have been shown to alter conductance at postsynaptic sites.

Amphetamines↗
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↗