Abstract: By the middle of the 20th century, development of powerful genetic approaches had ensured that the fruit fly would remain a model organism of choice for genetic and developmental studies. But in the 1970s, a few pioneering groups turned their attention to the prospect of using the fly for neurophysiological experiments. They proposed that in a poikilothermic organism such as Drosophila, temperature-sensitive or “ts” mutations in proteins that controlled nerve function would translate to a “ts” paralytic phenotype. This was by no means an obvious or even a likely assumption. However, following directed screens these groups soon reported dramatic demonstrations of reversible ts paralysis in fly mutants. Resultantly, these “simple” experiments led to the isolation of a number of conditional mutations including shibire, paralytic, and comatose. All have since been cloned and have enabled deep mechanistic insights into synaptic transmission and nerve conduction. comatose (comt) mutations, for example, were found to map to missense changes in dNSF1, a neuron-specific fly homolog of mammalian NSF (N-ethylmaleimide–sensitive fusion factor). Studies on comt were also some of the first to discriminate between nuanced models of NSF function during presynaptic transmitter release that have since been borne out by experiments in multiple preparations. Here, the authors present an overview of NSF function as it is understood today, with an emphasis on contributions from Drosophila beginning with experiments carried out by Obaid Siddiqi in the Benzer laboratory. The authors also outline initial results from a genetic screen for phenotypic modifiers of comt that hold the promise of further elucidating NSF function at the synapse. Over the years, the neuromuscular system of Drosophila has served as a uniquely accessible model to unravel mechanisms underlying synaptic transmission. To this day, ts paralysis remains one of the most emphatic demonstrations of nerve function in an intact organism. 相似文献
The purpose of this study was to examine whether positive changes in consciousness level after applying a sensory stimulation programme exceed natural recovery. A single experimental group interrupted time series design was used. Subjects were brain-injured patients who were hospitalized at a university hospital in South Korea. The sensory stimulation programme was composed of auditory, visual, olfactory, gustatory, tactile and physical stimulation. Levels of consciousness were evaluated using the Glasgow Coma Scale. The intervention was carried out twice, first for 4 weeks, then a recession period was allowed for 4 weeks, and immediately after this the second intervention was implemented for 4 weeks. Results showed significant alterations in consciousness levels 2 weeks after starting intervention 1. This effect increased gradually and was maintained for 3-4 weeks. However, consciousness levels began to decrease 2 weeks after terminating intervention 1 and this decrement continued until starting intervention 2. The pattern of improvement of intervention 1 could be represented as a gradual onset and temporary duration model. At the beginning of intervention 2, consciousness levels were maintained at a low level. However, they began to increase again after 2 weeks and this increment continued even after terminating intervention 2. Therefore, the effect of intervention 2 could be represented as a gradual onset and permanent duration model. These results suggest that an intervention programme should be applied for more than 1 month to achieve a permanent effect on consciousness levels and that at least 2 weeks are required for any significant effect. 相似文献
Current models of synaptic vesicle trafficking implicate a core complex of proteins comprised of N-ethylmaleimide-sensitive factor (NSF), soluble NSF attachment proteins (SNAPs), and SNAREs in synaptic vesicle fusion and neurotransmitter release. Despite this progress, major challenges remain in establishing the in vivo functions of these proteins and their roles in determining the physiological properties of synapses. The present study employs glutamatergic adult neuromuscular synapses of Drosophila, which exhibit conserved properties of short-term synaptic plasticity with respect to mammalian glutamatergic synapses, to address these issues through genetic analysis. Our findings establish an in vivo role for SNAP-25 in synaptic vesicle priming, and support a zippering model of SNARE function in this process. Moreover, these studies define the contribution of SNAP-25-dependent vesicle priming to the detailed properties of short-term depression elicited by paired-pulse (PP) and train stimulation. In contrast, NSF is shown here not to be required for WT PP depression, but to be critical for maintaining neurotransmitter release during sustained stimulation. In keeping with this role, disruption of NSF function results in activity-dependent redistribution of the t-SNARE proteins, SYNTAXIN and SNAP-25, away from neurotransmitter release sites (active zones). These findings support a role for NSF in replenishing active zone t-SNAREs for subsequent vesicle priming, and provide new insight into the spatial organization of SNARE protein cycling during synaptic activity. Together, the results reported here establish in vivo contributions of SNAP-25 and NSF to synaptic vesicle trafficking and define molecular mechanisms determining conserved functional properties of short-term depression. 相似文献
To evaluate the effectiveness of endoscopic surgery for life-threatening large brain hemorrhage, we reviewed our empirical cases of comatose patients with large supratentorial intracerebral hemorrhage. Among 35 patients with putaminal or subcortical hemorrhage that was evacuated endoscopically, 14 cases (40%) presented both findings of neurological grade IV for severity and hematoma volume exceeding 70 mL in the recent 3 years (endoscope group), whereas 8 cases with the same conditions were treated by conventional craniotomy for the preceding 3-year period (craniotomy group). Between these two groups, mean age was higher and duration of surgery was shorter in the endoscope group, but no significant differences in hematoma size or evacuation rate were recognized. In the 10 cases that presented with signs of cerebral herniation (neurological grade IVb) and required emergent decompression, the preparation time for surgery tended to be shorter in the endoscope group, although the difference was not significant. Additional ventricular drainage was performed in 7 cases and showed a supplemental effect of reducing intracranial pressure (ICP). Consequently, all patients in the endoscope group were rescued without decompressive large craniectomy, even with symptoms of cerebral herniation. In conclusion, endoscopic surgery has the potential to offer an effective therapeutic option for comatose patients with large supratentorial intracerebral hemorrhages, matching conventional craniotomy for emergent treatment in terms of mortality and management of ICP. 相似文献
Datura stramonium is a toxic plant member of the Solanaceae family. Its consumption may result in severe anticholinergic toxicity. We report the intoxication of 5‐ and 4‐year‐old brothers with Datura stramonium, which presented in two different manners. The first child presented agitation, hallucination and mydriasis that improved rapidly with benzodiazepine medication. The second presented comatose, mydriasis and Babinski signs. Gastric lavage and activated charcoal administration were performed. The child was intubated and mechanically ventilated until consciousness improvement. Datura stramonium poisoning may be considered by physicians in case of acute onset of decreased consciousness or behaviour trouble associated with anticholinergic signs and symptoms. 相似文献
Purpose: The evaluation and treatment for patients with prolonged periods of seriously impaired consciousness following traumatic brain injury (TBI), such as a vegetative or minimally conscious state, poses considerable challenges, particularly in the chronic phases of recovery.
Method: This blinded crossover study explored the effects of familiar auditory sensory training (FAST) compared with a sham stimulation in a patient seven years post severe TBI. Baseline data were collected over 4 weeks to account for variability in status with neurobehavioral measures, including the Disorders of Consciousness scale (DOCS), Coma Near Coma scale (CNC), and Consciousness Screening Algorithm. Pre-stimulation neurophysiological assessments were completed as well, namely Brainstem Auditory Evoked Potentials (BAEP) and Somatosensory Evoked Potentials (SSEP).
Results: Results revealed that a significant improvement in the DOCS neurobehavioral findings after FAST, which was not maintained during the sham. BAEP findings also improved with maintenance of these improvements following sham stimulation as evidenced by repeat testing.
Conclusions: The results emphasize the importance for continued evaluation and treatment of individuals in chronic states of seriously impaired consciousness with a variety of tools. Further study of auditory stimulation as a passive treatment paradigm for this population is warranted.
Implications for Rehabilitation
Clinicians should be equipped with treatment options to enhance neurobehavioral improvements when traditional treatment methods fail to deliver or maintain functional behavioral changes.
Routine assessment is crucial to detect subtle changes in neurobehavioral function even in chronic states of disordered consciousness and determine potential preserved cognitive abilities that may not be evident due to unreliable motor responses given motoric impairments.
Familiar Auditory Stimulation Training (FAST) is an ideal passive stimulation that can be supplied by families, allied health clinicians and nursing staff of all levels.