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S J Young

Publications and source records attributed to S J Young.

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

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↗
PubMed1979

Sites of action of amphetamine intrinsic to catecholaminergic nuclei: catecholaminergic presynaptic dendrites and axons.

1. It is now well established that the behavioral actions of amphetamine, especially locomotor and stereotyped behaviors, are dependent in part upon the release of catecholamines in the central nervous system. 2. A variety of empirical evidence has established that the release of catecholamines by amphetamine leads to changes in neuronal activity in regions postsynaptic to catecholaminergic nerve terminals. In addition, release of catecholamines is accompanied by a marked inhibition of neuronal firing in catecholaminergic neurons. 3. At least two conceptions have been advanced to account for this marked decrease in catecholaminergic neuronal activity. (a) In one of these, release of catecholamines from presynaptic terminals is thought to lead to a compensatory decrease in neuronal firing rate by means of a postsynaptic neuronal feedback loop from regions innervated by catecholaminergic neurons. (b) In the other, decreased neuronal activity is hypothesized to result from local release of catecholamines onto or near catecholaminergic neuronal dendrites and somata, a phenomenon that has been characterized as self-inhibition. 4. For dopaminergic neurons, recent biochemical, neuropharmacological and neuroanatomical evidence suggests that the latter process could be subserved by dopamine released from dopaminergic neuronal dendrites, i.e., "presynaptic" dendrites.

Amphetamine↗
PubMed1978

Phencyclidine-induced psychosis.

During a 13-month period, 9 patients with phencyclidine-induced psychosis were admitted to Darnall Army Hospital. They exhibited hostility agitation, and tangentiality and had delusions of influence and religious grandiosity. Six subjects reported auditory hallucinations, and 4 were disoriented in at least 1 sphere. Despite treatment with antipsychotic medication, the psychotic episodes often persisted for more than 30 days. Our clinical finding of prolonged psychotic reactions, together with previous reports of the effects of phencyclidine, suggests that phenycyclidine provides an intriguing drug model for schizophrenia.

Adolescent↗
PubMed1976

Psychiatric illness and the irritable bowel syndrome. Practical implications for the primary physician.

Twenty-nine consecutive outpatients with irritable bowel syndrome were given structured psychiatric interviews, as were 33 consecutive medical controls who did not have irritable bowel syndrome. All were from an internal medicine group practice. Seventy-two percent of irritable bowel syndrome subjects had psychiatric illness, with hysteria and depression the most prevalent syndromes. Only 18% of controls had psychiatric illness. The primary physician made an accurate psychiatric assessment in only 28% of the subjects. An awareness of his patient's psychiatric illness is necessary for the physician to provide effective treatment, as for depression, and to spare the patient needless medications, hospitalizations, and surgery, as with hysteria.

Colonic Diseases, Functional↗