Syndromes of schizophrenia. Classic literature.
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Biomedical subjects
Publications and source records attributed to T Crow.
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Intrinsic changes have been identified in isolated and intact type A and type B photoreceptors following classical conditioning of the nudibranch mollusk Hermissenda. Aspects of various intrinsic, nonsynaptic modifications are expressed by alterations in the excitability of identified photoreceptors in response to the conditioned stimulus. In addition to changes in cellular excitability, changes in synaptic strength between identified neurons have been proposed as a possible mechanism of associative learning in several invertebrate preparations. Here we report that classical conditioning produces differential effects upon the strength of inhibitory monosynaptic connections between identified pairs of type B and type A photoreceptors. The amplitude of IPSPs elicited by an action potential in the medial type B photoreceptor and recorded from medical type A photoreceptors was significantly enhanced in conditioned animals as compared to pseudorandom controls. In contrast, the amplitude of IPSPs elicited by an action potential in the lateral type B photoreceptor and recorded from lateral type A photoreceptors did not show significant synaptic enhancement following conditioning. These results provide additional evidence for differential effects of conditioning upon cellular modifications in identified type A and type B photoreceptors, and further indicate that multiple sites of cellular plasticity exist in the visual system of conditioned Hermissenda.
Serotonin (5-HT) produces both short- and long-term enhancement of generator potentials in identified type B-photoreceptors of Hermissenda. The actions of 5-HT have been shown to modulate both light- and voltage-dependent conductances. To further examine light-dependent processes we studied spontaneous and light-elicited discrete waves in the presence of 5-HT. Serotonin significantly increased the frequency of light-elicited discrete waves without initially increasing spontaneous discrete waves recorded in the dark. The increase in discrete wave frequency produced by 5-HT could not be described by a simple Poisson process, since the observed interval distribution after 5-HT application deviated significantly from the predicted exponential interval distribution.
One-trial conditioning of Hermissenda produces short- and long-term enhancement of generator potentials in identified type B-photoreceptors. The induction of short-term enhancement is blocked by kinase inhibitors and down-regulation of protein kinase C. We now report that established short- and long-term enhancement produced by one-trial conditioning is not reversed by the kinase inhibitors H-7 or sphingosine. These results indicate that persistent protein kinase C activity is not required in the maintenance or expression of enhancement.
When monozygotic twins are discordant for the diagnosis of schizophrenia, this discordance has been traditionally attributed to environmental factors acting upon a genome susceptible for the schizophrenia phenotype. The study presented here was designed to examine the occurrence of a genetic event, such as a postzygotic mitotic crossover, that could account for the discordance. Such a postzygotic event could affect cis-acting sequences and result in a phenotype of variable severity. We used molecular genetic methods to evaluate such an event with 94 microsatellite repeat polymorphic markers distributed on all autosomes and the X chromosome in five pairs of monozygotic twins discordant for schizophrenia. In this search, no genetic marker discordances were identified between the co-twins. The lack of a genetic difference may implicate nongenetic factors that are responsible in eliciting or suppressing the phenotype. However, the experiments performed in this study cannot eliminate the possibility that a tissue-specific mitotic crossover might have occurred in one of the discordant twins, which could not have been detected in our current study.
1. The visual system of Hermissenda has been studied extensively as a site of cellular plasticity produced by classical conditioning. Previous research has shown that one-trial conditioning, consisting of light paired with serotonin (5-HT) results in short- and long-term enhancement of light-elicited generator potentials in identified type B-photoreceptors. Recent evidence suggests that 5-HT exerts its effects on the induction of short-term enhancement by activation of protein kinase C (PKC), a Ca(2+)-activated and phospholipid-dependent protein kinase. However, the contribution of protein kinases in general, and specifically PKC in long-term enhancement has not been established. 2. The protein kinase inhibitors H-7 and sphingosine blocked the induction of short-term enhancement when applied before one-trial conditioning. However, the conditions that are sufficient to block the induction of short-term enhancement do not block long-term enhancement. Sphingosine and H-7 do not block the induction and expression of long-term enhancement when applied before one-trial conditioning. 3. Pretreatment before conditioning with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which leads to down-regulation of PKC, also did not block long-term enhancement. Down-regulation by itself did not produce enhancement, although the transient peak of light-elicited generator potentials was reduced by pretreatment with TPA. 4. The results suggest that the induction of short- and long-term enhancement involve parallel processes, and thus the expression of long-term cellular plasticity produced by one-trial conditioning does not depend on the induction or expression of short-term enhancement.
1. In identified photoreceptors in the eyes of Hermissenda, serotonin (5-HT) enhances the peak and plateau phases of light-evoked generator potentials and modulates light-dependent and voltage-dependent currents. In addition, electrophysiological and morphological studies indicate that 5-HT may contribute to cellular plasticity detected in the visual system of Hermissenda produced by classical conditioning procedures. With the use of conventional two-electrode voltage-clamp techniques, we examined the effects of 5-HT on three distinct currents recorded across the soma membranes of identified lateral and medial type B photoreceptors in the isolated circumesophageal nervous system. 2. The inward rectifier (Iir), a putative K(+)-dependent conductance, activates in 0-Na artificial seawater at membrane potentials greater than -60 mV, is voltage dependent, noninactivating, and reaches steady-state within 800 ms to 3 s at -100 mV. Bath application of 10(-4) M 5-HT consistently enhanced the magnitude of Iir at all potentials tested (-60 to -100 mV) and, in some cases, allowed expression of Iir, which was not initially detectable before the application of 5-HT. 3. The major component of outward K+ current in type B photoreceptors with IA and IK(Ca) blocked is the delayed rectifier [IK(v)]. 5-HT (10(-4) M) produced both an increase as well as a decrease in the peak amplitude of IK(v) and consistently slowed its inactivation rate and reduced twin-pulse inactivation. 4. A previously identified outward K+ current in type B photoreceptors has properties that are similar to the A current (IA).(ABSTRACT TRUNCATED AT 250 WORDS)
Classical conditioning of Hermissenda produces neurophysiological correlates in the primary sensory neurons of the pathway mediating the conditioned stimulus (CS), the type B and type A photoreceptors. Biophysical and biochemical changes intrinsic to the type B photoreceptors have been studied extensively in conditioned animals. A second site for intrinsic modification with learning has been recently identified in type A photoreceptors. We have recorded from identified medial and lateral type A photoreceptors in conditioned animals and animals that received pseudorandom presentations of light (CS) and rotation (unconditioned stimulus). Here we report that conditioning produces differential effects upon CS-elicited spike frequency and intrinsic excitability detected in identified lateral and medial type A photoreceptors. Lateral type A photoreceptors from conditioned animals exhibited significant increases in spike frequency elicited by the CS as compared to pseudorandom controls. In contrast, CS-elicited spike frequency recorded in medial type A photoreceptors was not significantly different from random controls. The amplitude of the peak and plateau phases of the generator potential of medial and lateral type A photoreceptors was decreased in conditioned animals as compared to random controls. In addition, only lateral type A photoreceptors exhibited enhanced cellular excitability as expressed by increased spike discharges produced by the injection of extrinsic depolarizing current pulses. Conditioning also decreased spike frequency accommodation in lateral type A photoreceptors. In normal controls, medial type B photoreceptors produced stronger synaptic inhibition of medial type A photoreceptors than the lateral type B photoreceptors inhibition of lateral type A photoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Light paired with serotonin (5-HT) in vivo produces both short- and long-term enhancement of generator potentials in identified B-photoreceptors in Hermissenda. The role of intracellular Ca2+ in the induction of enhancement in B-photoreceptors was assessed by buffering intracellular Ca2+ with the iontophoretic injection of BAPTA. Blocking light-elicited photoreceptor desensitization with BAPTA loading prior to applying 5-HT was used as an indication of the effectiveness of Ca2+ buffering. Enhancement was blocked in preparations that received BAPTA loading prior to the application of 5-HT while typical enhancement was elicited by light and 5-HT in control preparations. These results indicate that enhancement involves a Ca(2+)-dependent process.
Cellular correlates of classical conditioning were examined in two recently identified light responsive pedal neurons. The correlates of conditioning consisted of significant decreases in the pedal cells' responses to light (conditioned stimulus) recorded from conditioned animals compared to random controls. Pedal cell P7, which exhibits an inhibitory response to light in naive animals, showed significantly less inhibition during a 5 min light step in conditioned animals as compared to random controls. Pedal neuron P9, which exhibits an excitatory response to light in naive animals, showed significantly less excitation during a 10 s light step in conditioned animals as compared to random controls. The changes in the response to light recorded from pedal neurons P7 and P9 in conditioned animals were not accompanied by any significant changes in membrane potential, action potential amplitude or dark-adapted spike frequency.
The 1987 amendments to the Older Americans Act mandate a special effort to serve low-income minority elderly persons. A literature review showed that "practice-oriented" research on service use has focused primarily on identifying barriers with much less attention to identification of strategies for overcoming the barriers. This paper identifies and describes strategies used throughout Texas. Strategies addressing the "lack of knowledge" barrier included use of influential groups, working with significant individuals, and the media. Strategies addressing the "lack of access" barrier included transportation, affordability, and availability. Strategies addressing the "lack of intent" barrier focused on cultural differences, making services attractive, and overcoming negative attitudes toward service use.
As part of the analysis of the circuitry underlying phototaxis, 4 light-responsive pedal neurons were identified and characterized. The 4 newly identified neurons have been designated as pedal neurons P7, P8, P9 and P10. Pedal cell P7 has an inhibitory response to light, lasting several minutes. Pedal cells P8, P9 and P10 exhibit excitatory 'on' responses to light that last for a few seconds after light onset. Lucifer yellow fills showed that each identified pedal cell has only one process which exits the nervous system through one of the pedal nerves. Various procedures were used to investigate the responses to illumination expressed by the 4 identified pedal neurons. The results indicate that: (1) the light responses are not intrinsic, but are due to synaptic input from other light-responsive cell(s), and (2) the sources of the synaptic input to the pedal cells are the photoreceptors of the eye, and not extraocular photoreceptors or light sensitive neurons within the circumesophageal nervous system.
Light paired with serotonin (5-HT) in vivo produces both short and long-term enhancement of generator potentials in identified B-photoreceptors in Hermissenda. The contribution of protein kinase C to the induction of enhancement was assessed by pretreatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which produces a depletion or down-regulation of protein kinase C. Presentation of light and 5-HT after an 8 h pretreatment with TPA blocked the induction of enhancement of light-evoked generator potentials. Typical enhancement produced by light and 5-HT was observed after pretreatment with an inactive phorbol (4 alpha-phorbol). These results indicate that activation of protein kinase C is an important step in the induction of enhancement.
An in vivo conditioning procedure consisting of light paired with the direct application of 5-HT to the exposed but otherwise intact nervous system of Hermissenda produces a long-term modification of phototactic behavior. The long-term change in phototactic behavior produced by in vivo conditioning is dependent upon pairing light with 5-HT. In this paper, we investigate neural correlates of in vivo conditioning detected in 2 different identified photoreceptors. We found that in vivo conditioning produces a short-term and long-term enhancement of light-evoked generator potentials recorded from medial and lateral B-photoreceptors. We show that short-term enhancement is not dependent upon pairing light with 5-HT, is observed in both lateral and medial B-photoreceptors, and is expressed by a larger peak and plateau phase of light-evoked generator potentials. In contrast to short-term enhancement, we found that long-term enhancement is dependent upon pairing light with 5-HT, is detected in only lateral B-photoreceptors, and is expressed by a larger steady-state plateau phase of light-evoked generator potentials. We also present evidence that the direct action of 5-HT interacting with light- and/or voltage-dependent processes is sufficient to mimic the effects of in vivo conditioning on long-term enhancement. These results suggest that long-term enhancement may contribute to modified phototactic behavior in Hermissenda produced by 1-trial in vivo conditioning.
A one-trial in vivo conditioning procedure produces short- and long-term cellular changes that can be detected in identified sensory neurons of the pathway mediating the conditioned stimulus. The memory of the associative experience in the conditioned stimulus pathway is expressed by short- and long-term enhancement of light-evoked generator potentials recorded from identified lateral and medial type B photoreceptors within the eyes of Hermissenda. To identify mechanisms of the induction and expression of short- and long-term enhancement in identified photoreceptors, we have investigated the effects of inhibiting protein synthesis during the application of the one-trial in vivo conditioning procedure. Anisomycin (1 microM) present during and after the conditioning trial blocked long-term enhancement without affecting the induction or expression of short-term enhancement. Application of a control compound, deacetylanisomycin (1 microM), or delaying the application of anisomycin until 1 hr after the conditioning trial did not block either long- or short-term enhancement. These results indicate that synthesis of proteins during or shortly after training may be a critical step in the formation of long-term memory of the associative experience.
We report an unusual case of deep vein thrombosis following minor trauma in an adolescent who presented with a swollen, tender, lower extremity. Work-up consisted of a venogram which demonstrated occlusion of the deep venous system in the proximal leg. The patient was hospitalized for intravenous heparin followed by oral anticoagulation therapy. The problem of deep venous thrombosis in adolescents and the approach to diagnosis are discussed.
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A conditioning procedure consisting of pairing-specific stimulation of the eyes and gravity-detecting statocysts in Hermissenda results in a long-term modification of normal positive phototactic behavior. The learning is expressed by a significant suppression of the initiation of locomotion in the presence of light. We now report that an analogue of the classical conditioning procedure, consisting of light paired with serotonin (5-HT) applied directly to the exposed circumesophageal nervous system of otherwise intact animals, mimics the effect of conditioning on long-term changes in phototactic behavior. The effect of the conditioning analogue on behavior shows some specificity with 5-HT since light paired with dopamine or octopamine does not significantly affect phototactic behavior. The conditioning analogue exhibits pairing specificity since unpaired light and 5-HT and 5-HT applied in the dark do not produce behavioral suppression. Animals that initially received unpaired light and 5-HT do show behavioral suppression after receiving paired light and 5-HT. These results indicate that light (the conditioned stimulus) paired with the putative transmitter of the unconditioned stimulus pathway (5-HT) is sufficient to produce long-term phototactic suppression.