Dori Henderson

Optimization of a Goal Maintenance Task for Use in Clinical Applications

BACKGROUND We sought to develop a Dot Pattern Expectancy task (DPX) to assess goal maintenance for use in clinical trials. Altering the standard task created 5 versions of the DPX to compare-a standard version and 4 others. Alterations in the interstimulus interval (ISI) length and the strength of a learned prepotent response distinguished the different tasks. These adjustments were designed to decrease administration time and/or improve reliability of the data. METHODS We determined participant eligibility in an initial session (the first of 3) using clinical interviewing tools. The initial session also included a demographic assessment and assessments of community functioning and symptom severity. All versions of the DPX were administered, across 3 sessions. Specific deficits on the context processing compared with difficulty control condition were evaluated using mixed-effects logistic regression within a hierarchical linear model. RESULTS We analyzed the data from 136 control participants and 138 participants with schizophrenia. Relative to a difficulty control condition, patients performed worse than controls on context processing conditions that required goal maintenance. ISI did not predict errors. Stronger prepotency was associated with increased errors in the difficulty control relative to context processing condition for controls, which improved the interpretability of findings for patients. Reliability was acceptable for a version of the task with a 10-minute running time. CONCLUSIONS The best compromise between task duration and interpretability occurred on a version with a short ISI and a strong prepotency.

Thermal and Feeding Reactions of Pigeons during Food Scarcity and Cold

Birds living in the cold face energetic challenges from low ambient temperatures (Ta) as well as from food scarcity which often accompanies cold in nature. Birds react to low Ta with complex thermoregulatory and metabolic adjustments, and they also alter their foraging and feeding behavior rather dramatically when the availability of food becomes limited. In reaching a full understanding of adaptation to cold, it will be necessary to take into account the ways birds adapt to food scarcity as well as their thermal/metabolic adaptations to low Ta. This is a particularly interesting problem because of the interplay between thermoregulation and feeding. For example, when feeding strategies fail to produce sufficent food to maintain energy reserves, some birds reduce energy costs by lowering their body temperature (Tb). Also, exposure to cold not only activates the bird’s thermoregulatory defenses, but alters feeding strategies in a way that results in increased food intake if sufficient food is available in the environment. Furthermore, food intake has short term thermogenic consequences which can be significant in certain circumstances.

Cyclic GMP-activated channels of the chick pineal gland: Effects of divalent cations, pH, and cyclic AMP

Chick pineal cells maintained in dissociated cell culture express an intrinsic photosensitive circadian oscillator, but the mechanisms of phototransduction in avian pinealocytes are not fully understood. In this study, we have used inside-out patches to examine the characteristics of cyclic GMP-activated channels of chick pinealocytes in more detail, concentrating on the effects of factors known to modulate the secretion of melatonin and/or the function of circadian pacemakers. In most patches, the predominant conductance state was 19 pS in symmetrical 145 mM NaCl. But in some patches, a second cyclic GMP-activated channel with a unitary conductance of 29 pS was also present. The current flowing through cyclic GMP-activated channels was not affected by application of salines containing 1 μM Ca2+ to the cytoplasmic face of the patch membrane. By contrast, application of 1 mM Ca2+ caused a partial reduction in cyclic GMP-activated current at all membrane potentials. Application of 1–5 mM Mg2+ ions caused a virtually complete blockade of current at positive membrane potentials, but caused only a small decrease in current at negative membrane potentials. No obvious differences in the gating of cyclic GMP-activated channels were observed in pH 8.2, 7.4 or 6.2 salines. Application of salines containing 100 μM, 500 μM, or 1 mM cyclic AMP did not cause activation of the channels, but 5 mM cyclic AMP evoked a low level of channel activity. Application of 5 mM but not 100 μM cyclic AMP decreased the probability of channel activation caused by 20–100 μM cyclic GMP and also increased the percentage of openings to an 11 pS subconductance state. Thus, cyclic AMP acts as a weak partial agonist. Nevertheless, the gating of these channels does not seem to be controlled directly by physiologically relevant changes in intracellular Ca2+, pH, or cyclic AMP.

Calcium channel immunoreactivity in the salamander retina

This study reports the distribution of the α1D and α1E calcium channel subunits in the neotenous tiger salamander retina based on immunohistochemical techniques. Confocal and light microscopy were used to localize staining with fluorescently tagged antibodies to α1D and α1E in cross-sectional and flatmount preparations of retina. α1D-immunoreactivity (α1D-IR) was localized to the inner and outer plexiform layers (IPL and OPL, respectively), ganglion cell layer (GCL), and optic fiber layer. α1E-IR was found predominantly in the IPL, with scattered, weak representation in the OPL. α1E-IR was not detected in the GCL or fiber layer. These findings suggest that different α1 calcium channel proteins have distinctive distributions in retina, which may reflect their unique and different roles in retinal processing and homeostasis.

Ingestive behavior and body temperature of pigeons during long-term cold exposure.

Pigeons well adapted to living in 21 degrees C ambient temperature (T(a)) were continuously exposed to cold T(a) for 6 days (Experiment 1) or 30 days (Experiment 2). The pigeons lived on a 12:12 L:D cycle where they could obtain short access to food and water at any time in the light phase by making 12 keypeck responses. Across the two experiments, the levels of cold exposure were 6 degrees C, 1 degrees C, and 0.6 degrees C. In cold, total daily food intake increased gradually across the first few days of the exposure, and the new level of food intake was inversely related to T(a). The daily ratio of total water drunk to total food eaten averaged approximately 1.3 in 21 degrees C, fell to approximately 1.0 on day 1 of cold exposure, and remained at that level for as long as 30 days. The day-night cycle in core body temperature was not changed by cold exposure. The bimodal temporal pattern of feeding in the light phase, which is characteristic of pigeons in moderate T(a), was preserved in the cold although the absolute level of feeding activity was enhanced. An analysis of the ways individual pigeons achieved total daily food intake by combining a number of feeding episodes with an average amount eaten per episode revealed considerable variation between birds, but a relatively constant feeding style within bird over time. In the colder temperatures used, however, the pigeons all increased the number of feeding episodes per day. The results provide the first detailed analysis of cold-induced changes in ingestive behavior in the pigeon and raise several questions about the behavioral expression of cold-sensitive regulatory processes.

Voltage- and Ca2+-activated ionic currents in acutely dissociated cells of the chick pineal gland

Previous research on cultured chick pineal cells suggests that melatonin production is modulated by Ca2+ influx through voltage-dependent Ca2+ channels. The possible existence of other ionic currents was investigated by means of whole-cell recordings from acutely isolated cells. Several different inward and outward currents were identified. Inward currents included L-type Ca2+ currents and voltage-activated tetrodotoxin (TTX)-sensitive Na+ currents. Sodium currents have not been reported previously in pineal cells of any species. These two inward currents were present in the majority of cells. Chick pineal cells also expressed several types of voltage-dependent and Ca(2+)-dependent K+ currents that differed in voltage dependence, kinetics, and pharmacology. These included two Ca(2+)-dependent outward currents which differed in sensitivity to tetraethylammonium chloride (TEA), and at least two distinct voltage-activated K+ currents. Considerable cell-to-cell variation in the amplitude and nature of the evoked outward currents was observed. These ionic currents may be important for the regulation of melatonin synthesis and the modulation of circadian rhythmicity.

Evidence for low-voltage-activated (LVA) calcium currents in the dendrites of tiger salamander retinal ganglion cells.

We have evaluated the spatial distribution of low-voltage-activated calcium currents in ganglion cells of the tiger salamander retina. Whole-cell recordings were obtained from ganglion cells in a retinal slice preparation and from acutely dissociated ganglion cells that were identified through retrograde dye injection. In single dissociated cells, we estimated the magnitude (pA) and current density (pA/pF) of LVA currents in ganglion cells, both with and without dendritic processes. Ganglion cells that retained a portion of their dendritic arbor had larger LVA calcium currents and higher LVA current densities than those which lacked processes. When cell capacitance measurements were used to derive the surface area of the soma and dendritic processes, we concluded that a higher LVA current density was present in the dendrites; we estimate that, on average, the current density in the dendrites is approximately five times that of the soma. The presence of a significant density of LVA calcium channels in the dendrites of ganglion cells suggests that they could be involved in a number of cellular functions, including dendritic integration of synaptic currents, impulse generation, and homeostatic functions related to changes in the intradendritic calcium concentration.

Low-voltage activated calcium currents in ganglion cells of the tiger salamander retina: Experiment and simulation

We examined the functional properties of a low-voltage-activated (LVA) calcium current in ganglion cells of the neotenous tiger salamander (Ambystoma tigrinum) retina. Our analysis was based on whole-cell recordings from acutely dissociated ganglion cell bodies identified by retrograde dye injections. Using a continuously perfused cell preparation, the LVA current was isolated with the use of potassium channel blocking agents added to the bathing medium and the pipette solution, while tetrodotoxin was added to the bathing medium to block Na+ channels. Approximately 70% of ganglion cells had an easily identified LVA current. The LVA current activated at membrane potentials more positive than -90 mV, and inactivated rapidly. It was relatively insensitive to nickel (IC50 > 500 microM) and amiloride (IC50 > 750 microM). Voltage- and current-clamp studies allowed us to generate a model of this current using the NEURON simulation program. Studies were also carried out to measure the LVA Ca2+ current in ganglion cells with dendrites to confirm that it had a significant dendritic representation. Physiological mechanisms that may depend on LVA Ca2+ currents are discussed with an emphasis on the role that dendrites play in ganglion cell function.