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Biomedical subjects

R W Greene

Publications and source records attributed to R W Greene.

At least 37 records · Page 2Linked to original sources
PubMed1996

NMDA-dependent modulation of CA1 local circuit inhibition.

Whole-cell and extracellular recording techniques were used to examine local circuit inhibition in the CA1 region of the rat hippocampus in vitro. Activation, primarily of the recurrent inhibitory circuit by alvear stimulation, elicited an IPSP in pyramidal neurons that was dependent, in part, on NMDA receptor activation. Application of a tetanizing stimulus to the alveus evoked long-term potentiation (LTP) of the intracellularly recorded recurrent IPSPs. This LTP also was NMDA-dependent and was more sensitive to blockade by the NMDA antagonists 2-amino-5-phosphonovalerate (APV) and N-acetyl-aspartyl-glutamate, than the excitatory LTP produced by Schaffer collateral stimulation. With regard to APV, the sensitivity of inhibitory LTP was an order of magnitude greater. A biophysical simulation of hippocampal CA1 circuitry was used in a model of learned pattern recognition that included LTP in both excitatory and inhibitory recurrent circuits. In this model, selective blockade of inhibitory LTP produced aberrant spread of lateral excitation, resulting in confusion of normally distinguishable patterns of neuronal activity. Consideration is given to the possibility that selective disruption of NMDA-dependent modulation of local circuit inhibition may serve as a model for some aspects of dysfunction associated with NMDA-antagonist exposure and schizophrenia.

2-Amino-5-phosphonovalerate↗
PubMed1996

Glycine-mediated inhibitory postsynaptic potentials in the medial pontine reticular formation of the rat in vitro.

Glycinergic neurotransmission was examined in rat medial pontine reticular formation neurons in vitro. Intracellular recordings using glass microelectrodes were made in acutely prepared brainstem slices 400 microns thick. Spontaneous and electrically evoked synaptic activity was blocked by the glycine antagonist strychnine (1-5 microM) but not by the GABA antagonists bicuculline methiodide (40 microM) or picrotoxin (40 microM). Strychnine-sensitive spontaneous and evoked postsynaptic potentials persisted in the presence of the glutamate antagonist (kynurenate, 1 mM). Whole-cell voltage-clamp recordings were carried out in organotypic cultures of rat brainstem. The reversal potential of synaptic currents and responses to exogenously applied glycine were similar and were sensitive to manipulations of the chloride equilibrium potential. Synaptic activity but not responses to exogenous glycine were blocked by tetrodotoxin (0.3 microM). These results indicate the presence of robust, chloride ion-mediated glycinergic inhibition of medial pontine reticular formation neurons, and suggest that glycinergic neurons play an important role in controlling pontine premotor circuitry.

Animals↗
PubMed1996

Toward a new psychometric definition of social disability in children with attention-deficit hyperactivity disorder.

OBJECTIVE: To investigate a new mechanism for identifying social disability in children with attention-deficit hyperactivity disorder (ADHD), employing psychometric methodology used in defining learning disabilities. METHOD: Two groups of index children were examined: 140 children with ADHD (referred from both psychiatric and pediatric sources) and 120 non-ADHD comparison children. Subjects were defined as socially disabled if they had a value greater than 1.65 on a standardized discrepancy score between observed and expected scores on a measure of social functioning (with expected scores derived as a function of the child's estimated Full Scale IQ). Children identified as socially disabled were compared with non-socially disabled probands on psychopathology, familiality, cognitive functioning, school history, and treatment history. RESULTS: Using this psychometric approach, 22% of the ADHD probands qualified as socially disabled, whereas none of the comparison probands qualified (p < or = .001). Socially disabled ADHD probands were significantly more impaired than were non-socially disabled ADHD probands in global and specific measures of social functioning and patterns of psychiatric comorbidity. CONCLUSIONS: The psychometrically defined construct of social disability may identify children with ADHD who are at very high risk for severe social dysfunction and whose course and prognosis may vary from those of other children with ADHD. This subgroup of children with ADHD may be at heightened risk for poor outcome, and their identification may facilitate the development of clinical interventions aimed at ameliorating their specific difficulties.

Adolescent↗
PubMed1996

Is childhood oppositional defiant disorder a precursor to adolescent conduct disorder? Findings from a four-year follow-up study of children with ADHD.

OBJECTIVE: To evaluate the overlap between attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), addressing whether ODD is subsyndromal form of conduct disorder (CD) and, if so, whether it is a precursor or prodrome syndrome of CD. METHOD: Assessments from multiple domains were used to examine 140 children with ADHD and 120 normal controls at baseline and 4 years later. RESULTS: Of children who had ADHD at baseline, 65% had comorbid ODD and 22% had CD. Among those with ODD, 32% had comorbid CD. All but one child with CD also had ODD that preceded the onset of CD by several years. ODD+CD children had more severe symptoms of ODD, more comorbid psychiatric disorders, lower Global Assessment of Functioning Scale scores, more bipolar disorder, and more abnormal Child Behavior Checklist clinical scale scores compared with ADHD children with non-CD ODD and those without ODD or CD. In addition, ODD without CD at baseline assessment in childhood did not increase the risk for CD at the 4-year follow-up, by midadolescence. CONCLUSIONS: Two subtypes of ODD associated with ADHD were identified: one that is prodromal to CD and another that is subsyndromal to CD but not likely to progress into CD in later years. These ODD subtypes have different correlates, course, and outcome.

Adolescent↗
PubMed1994

Abnormal fear response and aggressive behavior in mutant mice deficient for alpha-calcium-calmodulin kinase II.

Mice deficient for the gene encoding alpha-calcium-calmodulin-dependent kinase II (alpha-CaMKII knockout mice) provide a promising tool to link behavioral and cellular abnormalities with a specific molecular lesion. The heterozygous mouse exhibited a well-circumscribed syndrome of behavioral abnormalities, consisting primarily of a decreased fear response and an increase in defensive aggression, in the absence of any measured cognitive deficits. Unlike the heterozygote, the homozygote displayed abnormal behavior in all paradigms tested. At the cellular level, both extracellular and whole-cell patch clamp recordings indicated that serotonin release in putative serotonergic neurons of the dorsal raphe was reduced. Thus, alpha-CaMKII knockout mice, in particular the heterozygote, may provide a model for studying the molecular and cellular basis underlying emotional disorders involving fear and aggression.

Aggression↗
PubMed1994

Adenosine inhibition of mesopontine cholinergic neurons: implications for EEG arousal.

Increased discharge activity of mesopontine cholinergic neurons participates in the production of electroencephalographic (EEG) arousal; such arousal diminishes as a function of the duration of prior wakefulness or of brain hyperthermia. Whole-cell and extracellular recordings in a brainstem slice show that mesopontine cholinergic neurons are under the tonic inhibitory control of endogenous adenosine, a neuromodulator released during brain metabolism. This inhibitory tone is mediated postsynaptically by an inwardly rectifying potassium conductance and by an inhibition of the hyperpolarization-activated current. These data provide a coupling mechanism linking neuronal control of EEG arousal with the effects of prior wakefulness, brain hyperthermia, and the use of the adenosine receptor blockers caffeine and theophylline.

Adenosine↗
PubMed1994

Effect of metabolic alterations on the accumulation of technetium-99m-labeled d,l-HMPAO in slices of rat cerebral cortex.

It is widely recognized that the distribution of technetium-99m-labeled d,l-hexamethylpropylene amine oxime (99mTc-HMPAO) in the brain is determined by the regional blood flow. However, other factors may affect this process including the metabolism of the brain tissue. To examine this possibility we studied the effects of metabolic alterations on 99mTc-HMPAO uptake in rat brain cortex slices, with concurrent measurement of oxygen consumption (QO2). 99mTc-HMPAO uptake was determined by incubating slices of rat cerebral cortex at 37 degrees C in Krebs-Ringer phosphate glucose medium containing 99mTc-HMPAO with and without test substances. Differential gradients for 99mTc activity between the tissue and the suspending medium (T/M ratio) were derived from the equation T/M[99mTc] = counts per gram of tissue/counts per milliliter of medium. The QO2 of the brain slices was measured using a biological oxygen monitor equipped with a polarographic oxygen probe. Inhibitors affecting oxidative phosphorylation caused parallel suppression of the T/M ratio and QO2. Agents that uncouple oxidation from phosphorylation increased the QO2 and decreased the T/M ratio. Incubation of slices at 22 degrees C depressed the T/M ratio and QO2. The presence of inhibitors of oxidative phosphorylation in the incubation medium increased the release of 99mTc activity from slices that had been prelabeled with 99mTc-HMPAO. These findings suggest that the altered metabolic status of the brain tissue modulates the kinetics and net accumulation of 99mTc-HMPAO at the cellular level by either depressing uptake, increasing back-diffusion, or both.

2,4-Dinitrophenol↗
PubMed1994

The mechanism of noradrenergic alpha 1 excitatory modulation of pontine reticular formation neurons.

The alpha 1 adrenergic receptor occurs in all major divisions of the CNS and is thought to play a role in all behaviors influenced by norepinephrine (NE). In the medial pontine reticular formation (mPRF), the proposed site of adrenergic enhancement of startle responses (Davis, 1984), alpha 1 agonists excite most neurons (Gerber et al., 1990). We here report that alpha 1 excitation results from a reduction of a voltage- and calcium-dependent potassium current, not previously recognized as ligand-modulated. The calcium sensitivity is suggested by its antagonism with Mg2+, Cd2+, Ba2+, low concentrations of tetraethylammonium, and charybdotoxin. The voltage sensitivity of this conductance falls within the membrane potential range critical to action potential generation. Based on this voltage sensitivity, the change in repetitive firing characteristics may be predicted according to a mathematical model of the mPRF neuronal electrophysiology. The predicted response to a 50% decrease in the phenylephrine (PE)-sensitive conductance is similar to the observed responses, with respect to both the current response under voltage-clamp conditions and alterations of the AHP and frequency/current curve. In contrast, modeling a reduction of a voltage-insensitive leak current predicts none of these changes. Thus, the noradrenergic reduction of this current depolarizes the membrane, increases the likelihood of an initial response to depolarizing input, and increases firing rate during sustained depolarization in a manner consistent with an NE role as an excitatory neuromodulator of the mPRF.

Animals↗
PubMed1993

Nicotinic depolarizations of rat medial pontine reticular formation neurons studied in vitro.

Either muscarinic or nicotinic cholinergic activation of the medial pontine reticular formation evokes a behavioral state, indistinguishable in most respects from that of natural rapid eye movement sleep. However, the presence of physiologically relevant nicotonic receptors has not been described. Intracellular current and single electrode voltage clamp recordings were used to analyse the electrophysiological responses of rat medial pontine reticular formation neurons to nicotinic activation in vitro. In response to the nicotonic agonist, 1,1-dimethyl-4-phenylpiperazinium iodine, depolarization in association with an inward current was observed in 70% of the medial pontine reticular formation neurons. This effect was insensitive to the muscarinic antagonist atropine and the nicotinic ganglionic antagonists mecamylamine and hexamethonium. However, the neuromuscular nicotinic antagonist D-tubocurare and dihydro-beta-erythroidine were effective. This is consistent with a cholinergic activation of medial pontine reticular formation neurons evoking a rapid eye movement sleep-like behavioral state, at least in part, by nicotinic receptors on these neurons.

Animals↗
PubMed1993

Inhibitory action of muscarinic agonists on neurons in the rat laterodorsal tegmental nucleus in vitro.

1. The effects of the mixed cholinergic agonist carbachol and the muscarinic agonist methacholine (MCh) on neurons of the laterodorsal tegmental nucleus (LDT) were studied with the use of intracellular and whole-cell patch-clamp recordings in a rat brain stem slice preparation. 2. Neurons were classified into one of two categories on the basis of their intrinsic membrane properties: those that displayed a prominent low-threshold calcium burst (LTB, 60%) and those that did not exhibit such a burst (non-LTB, 40%). 3. Neurons from which recordings were obtained were filled with biocytin, visualized with Texas-red avidin, and identified as cholinergic or noncholinergic with NADPH-diaphorase histochemistry. Eighty percent of the LTB neurons that were processed in this manner were cholinergic, and 60% of the non-LTB neurons were cholinergic. 4. Carbachol elicited a membrane hyperpolarization associated with a decrease in input resistance in 95% of the cells tested. Under voltage clamp this response was shown to be due to an outward current that reversed near the equilibrium potential for potassium and displayed marked inward rectification. The conductance/voltage relationship was fit to the Boltzmann equation with a mean V1/2 = -73 +/- 4 (SD) mV and a mean k value of 10 +/- 4. The carbachol-evoked current was fully blocked by extracellular barium. 5. There was no significant effect of carbachol on the transient currents IA or IT. 6. The carbachol-evoked current was mimicked by the specific muscarinic agonist methacholine and blocked by high concentrations of the muscarinic receptor antagonist pirenzepine (IC50 = 580 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1992

Distribution of NADPH-diaphorase positive somata in the brainstem of the monitor lizard Varanus exanthematicus.

The distribution and size of presumptive cholinergic somata in the brainstem of the Savanna monitor lizard Varanus exanthematicus were determined using the enzyme histochemical marker NADPH-diaphorase. Numerous neurons were labelled in the lizard brainstem with this technique. A three dimensional computer reconstruction of this population revealed that it shows marked similarity to the laterodorsal tegmental/pedunculopontine tegmental cholinergic cell column, an NADPH-diaphorase positive population in the mesopontine tegmentum of the mammalian brainstem.

Animals↗
PubMed1992

Serotonin hyperpolarizes cholinergic low-threshold burst neurons in the rat laterodorsal tegmental nucleus in vitro.

Serotonergic suppression of cholinergic neuronal activity implicated in the regulation of rapid eye movement sleep and its associated phenomenon, pontogeniculooccipital waves, has long been postulated, but no direct proof has been available. In this study, intracellular and whole-cell patch-clamp recording techniques were combined with enzyme histochemistry to examine the intrinsic electrophysiological properties and response to serotonin (5-HT) of identified cholinergic rat laterodorsal tegmental nucleus neurons in vitro. Sixty-five percent of the recorded neurons demonstrated a prominent low-threshold burst, and of these, 83% were cholinergic. In current-clamp recordings 64% of the bursting cholinergic neurons tested responded to the application of 5-HT with a membrane hyperpolarization and decrease in input resistance. This effect was mimicked by application of the selective 5-HT type 1 receptor agonist carboxamidotryptamine maleate. Whole-cell patch-clamp recordings revealed that the hyperpolarizing response was mediated by an inwardly rectifying K+ current. Application of 5-HT decreased excitability and markedly modulated the discharge pattern of cholinergic bursting neurons: during a 5-HT-induced hyperpolarization these neurons exhibited no rebound burst after hyperpolarizing current input and a burst in response to depolarizing current input. In the absence of 5-HT, the relatively depolarized cholinergic bursting neurons responded to an identical hyperpolarizing current input with a burst and did not produce a burst after depolarizing current input. These data provide a cellular and molecular basis for the hypothesis that 5-HT modulates rapid eye movement sleep phenomenology by altering the firing pattern of bursting cholinergic neurons.

Action Potentials↗
PubMed1992

Adenosine-mediated synaptic inhibition: partial blockade by barium does not prevent anti-epileptiform activity.

Adenosine-induced inhibition of evoked postsynaptic potentials (PSPs) and epileptiform burst firing in the CA1 subfield of rat hippocampal slices was studied with intracellular recordings in vitro. Adenosine (50 microM) caused a membrane hyperpolarization which was abolished during superfusion with 2 mM Ba2+. The adenosine-induced inhibition of the PSPs was still evident, although the magnitude of the effect was significantly reduced. Adenosine also reduced Ba(2+)-induced burst firing, but less effectively than it did bursts evoked by TEA (5 mM). The results suggest that adenosine inhibits synaptic transmission and epileptiform activity by at least 2 mechanisms: a postsynaptic barium-sensitive increase in gK and a presynaptic effect independent of this adenosine-evoked outward potassium conductance.

Action Potentials↗
PubMed1992

Serotonin1 and serotonin2 receptors hyperpolarize and depolarize separate populations of medial pontine reticular formation neurons in vitro.

The action of serotonin on medial pontine reticular formation neurons was examined using intracellular electrophysiological methods in rat brainstem slices in vitro. A hyperpolarization associated with a decrease in input resistance was elicited by serotonin in 34% of the neurons, and a depolarization associated with an increase in input resistance was produced in 56% of the neurons. Both responses persisted in the presence of tetrodotoxin. The hyperpolarization resulted from a steady-state increase in outward current which varied with the external potassium concentration in a manner consistent with a conductance increase primarily to this ion. This response was mimicked by the serotonin1 agonist, 5-carboxamidotryptamine, as well as by the serotonin1a agonist, 8-hydroxy-dipropyl aminotetralin hydrobromide, and was blocked by spiperone, an antagonist of serotonin1 sites. The depolarization resulted from a steady-state decrease in outward current which varied with external potassium. The depolarization was mimicked by the serotonin2 agonist, alpha-methyl-5-hydroxytryptamine, and was blocked by the serotonin2 antagonist, ketanserin. Neither of these agents had any effect upon serotonin-induced hyperpolarizations. In conclusion, the excitability of medial pontine reticular formation neurons is influenced by serotonin acting to increase or decrease potassium conductance(s). These opposing effects reflect actions on distinct serotonin receptor subtypes that are segregated to distinct populations of medial pontine reticular formation neurons.

Animals↗
PubMed1992

Sociometric status and academic, behavioral, and psychological adjustment: a five-year longitudinal study.

Six hundred fourth-graders rated how much they liked to play with each of their classmates and then nominated their three best friends; 296 of the 600 children were assigned sociometric classifications of popular, neglected, average, controversial, or rejected status (the remaining 304 children failed to meet inclusion criteria). Five years later, 267 of the 296 classified children (90.2%) were evaluated on measures of academic performance, social behavior, and psychological adjustment. The number and type of contacts with the juvenile justice system were also determined. In general, children classified as rejected or controversial tended to fare more poorly on indices of long-term adjustment than did children classified as popular, neglected, or average. Results are discussed in terms of the predictive validity of sociometric rating and nomination procedures and their utility in identifying children at risk for later maladjustment.

Achievement↗
PubMed1992

Excitatory amino acid-mediated responses and synaptic potentials in medial pontine reticular formation neurons of the rat in vitro.

Neurons of the medial pontine reticular formation (mPRF) are involved in the execution of numerous behaviors including initiation of locomotion, eye movements, startle responses, and rapid eye movement sleep phenomena. Approximately half of the afferent projections to mPRF neurons come from within the reticular formation (Shammah-Lagnado et al., 1987). In spite of the importance of reticulo-reticular connections, virtually nothing is known about transmitters mediating these synapses. In order to identify a candidate excitatory neurotransmitter, the actions of excitatory amino acids (EAAs) on the membrane properties of mPRF neurons recorded in rat brainstem slices in vitro were studied. Standard intracellular recording methods, including single-electrode voltage clamp, were used to examine the postsynaptic actions of EAAs. We also tested whether EAA antagonists block EPSPs evoked by stimulation of the contralateral reticular formation in the slices. mPRF neurons responded to both non-NMDA and NMDA agonists. NMDA-induced conductances were voltage dependent and depressed by physiological concentrations of magnesium. Stimulation of the contralateral reticular formation elicited EPSPs that were depressed by the general EAA antagonist kynurenate. Evoked EPSPs were partially depressed by 6,7-dinitroquinoxaline-2,3-dione. The evoked EPSP was further reduced by the NMDA antagonist (+/-)-2-amino-5-phosphonopentanoic acid in some cases. These results suggest that excitatory reticulo-reticular neurotransmission is mediated by an EAA. Both non-NMDA and NMDA receptors contribute to EAA neurotransmission in the mPRF formation and play an integral role in reticular formation function.

Amino Acids↗
PubMed1991

Sociometric status: its stability and validity among neglected, rejected and popular children.

Although important distinctions among sociometrically rejected, neglected, and popular children have been reported in the literature, concerns have been raised about use of negative peer nominations in identifying these children. A revised procedure developed by Asher and Dodge [Developmental Psychology, 22, 444-449 (1986)] eliminates the need to obtain negative peer nominations. In the present study, the construct validity of this revised procedure was explored and its long-term stability examined over 6, 12 and 18 months. Our findings establish significant differences on several indices among rejected, neglected and popular children. However, the differences between rejected and popular children were more robust than those between neglected and popular children, who failed to differ from one another on most of the measures. Moreover, fairly good long-term stability was found for popular and rejected status, whereas the long-term stability for neglected status was quite poor. These findings were addressed in the context of similar research employing negative nomination methods. Implications for the identification of at-risk children were also discussed.

Aggression↗