Activity-dependent plasticity is a critical component of nervous systems. We show that in Caenorhabditis elegans, worms raised in isolation made smaller responses to mechanosensory stimulation and were smaller and slower to begin laying eggs than age-matched group-raised worms. The glutamate receptor gene GLR-1 was critical for the observed alterations in behavior but not in size, whereas the cGMP-dependent protein kinase gene EGL-4 was critical for the observed changes in size but not the changes in behavior. Mechanosensory stimulation during development reversed the effects of isolation on behavior and began to reduce the effects of isolation on size. In C. elegans, the six mechanosensory touch neurons synapse onto the four pair of command interneurons for forward and backward movement. Touch (mechanosensory) neurons of worms raised in isolation expressed lower levels of green fluorescent protein (GFP)-tagged synaptobrevin than touch neurons of worms raised in colonies. Command interneurons of worms raised in isolation expressed lower levels of GFP-tagged glutamate receptors than command interneurons of worms raised in groups. Brief mechanical stimulation during larval development rescued the expression of GFP-tagged glutamate receptors but not GFP-tagged synaptobrevin. Together, these results indicate that the level of stimulation experienced by C. elegans during development profoundly affects the development of neuronal connectivity and has widespread cellular and behavioral consequences.
In these studies the nematode Caenorhabditis elegans was used as a model to investigate ways to reverse the effects of mechanosensory deprivation on behavior and development. Rose et al. (J Neurosci 2005; 25:7159-7168) showed that worms reared in isolation responded significantly less to a mechanical tap stimulus, were significantly smaller, and expressed significantly lower levels of a postsynaptic glutamate receptor subunit on the command interneurons of the tap response circuit and a presynaptic vesicle marker in the tap sensory neurons compared with worms raised in groups. Here, brief mechanical stimulation at any time throughout development reversed the effects of isolation on the response to tap and on postsynaptic glutamate receptor expression on the command interneurons, suggesting there is no critical period for these measures. In contrast to the high level of plasticity in glutamate receptor subunit expression on the interneurons, low levels of stimulation only rescued vesicle expression in the tap sensory neurons early in development and progressively higher levels of stimulation were required as the worm developed, suggesting a sensitive period immediately after hatching, followed by a period of decreasing plasticity. Stimulation during the first three stages of larval development, but not later, rescued the effects of isolation on worm length, suggesting there is a critical period for this measure that ends in the third larval stage. These results indicate that different effects of early isolation required different amounts and/or timing of stimulation to be reversed.
a b s t r a c tEpidemiological evidence suggests a link between chronic oxygen starvation and fat accumulation/ obesity, however the underlying mechanism remains unclear. Using Caenorhabditis elegans we found extended oxygen deprivation resulted in activation of SBP-1, the worm homologue of SREBP1, a transcription factor important in maintaining lipid homeostasis. SBP-1 knockdown prevented hypoxia-induced fat accumulation and the associated increase in worm width/length ratio, demonstrating that SBP-1/SREBP1 plays an essential role in hypoxia-induced lipid accumulation and body shape alteration. This study provides the first evidence suggesting that activation of SREBP1 may be a critical pathogenic factor contributing to chronic hypoxia associated excessive fat accumulation/ obesity in humans.
Across health care disciplines research reflects the usefulness of integrating computer technology into administrative and clinical practices. Electroconvulsive therapy (ECT) researchers are often interested in examining 3 primary areas: patient characteristics, treatment characteristics, and treatment outcomes. Generating reports and conducting research analysis via the traditional patient chart review are a time-consuming and costly method. At Riverview Hospital, a tertiary care psychiatric hospital, the active use of a clinical database for patients receiving ECT allows for detailed treatment tracking and evaluation of pretreatment and posttreatment patient outcome measures. Initially, designed as part of a quality improvement process to readily access patient information and generate periodic reports, the ECT clinical database is now a central resource for ECT-specific patient, treatment, and outcome tracking. The relevance, design, content variables, and subsequent functions of the entry and storage of ECT-related administrative, treatment, outcome, and patient factors are clearly outlined and discussed. Strengths and limitations to the existing database are shared. Recommendations to other ECT services to implement this valuable documentation strategy are addressed. This approach can be an invaluable tool in providing the field of psychiatry with further contributions to ECT clinical outcomes.
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