The slow and regular pacemaking activity of midbrain dopamine (DA) neurons requires proper spatial organization of the excitable elements between the soma and dendritic compartments, but the somatodendritic organization is not clear. Here, we show that the dynamic interaction between the soma and multiple proximal dendritic compartments (PDCs) generates the slow pacemaking activity in DA neurons. In multipolar DA neurons, spontaneous action potentials (sAPs) consistently originate from the axon-bearing dendrite. However, when the axon initial segment was disabled, sAPs emerge randomly from various primary PDCs, indicating that multiple PDCs drive pacemaking. Ca2+ measurements and local stimulation/perturbation experiments suggest that the soma serves as a stably-oscillating inertial compartment, while multiple PDCs exhibit stochastic fluctuations and high excitability. Despite the stochastic and excitable nature of PDCs, their activities are balanced by the large centrally-connected inertial soma, resulting in the slow synchronized pacemaking rhythm. Furthermore, our electrophysiological experiments indicate that the soma and PDCs, with distinct characteristics, play different roles in glutamate-induced burst-pause firing patterns. Excitable PDCs mediate excitatory burst responses to glutamate, while the large inertial soma determines inhibitory pause responses to glutamate. Therefore, we could conclude that this somatodendritic organization serves as a common foundation for both pacemaker activity and evoked firing patterns in midbrain DA neurons.

PURPOSE:Prolonged cold ischemia has been shown to be an important factor in the development of post-transplant renal dysfunction. The exact mechanisms have not been completely defined. The expression of ICAM-1 (CD-54) in rat kidneys stored at 0, 4, 12, 24 and 48 hours in University of Wisconsin (UW) solution was studied in an attempt to correlate ischemia time with increased immunogenicity of the graft. METHODS: Kidneys from male Lewis rats were perfused with UW solution, removed and bathed in UW solution at 4 degrees C for 4, 12, 24, and 48 hours respectively. For the evaluation of expression of ICAM-1, immunohistochemical staining, Western blotting and RT-PCR were performed. RESULTS: Immunohistochemical staining in normal non-ischemic kidneys revealed that glomerular capillaries expressed ICAM-1 but that tubular cells did not. The preserved kidneys were analyzed with immunohistochemistry, Western blotting and semi-quantitative RT-PCR and showed increased transcription and expression of ICAM-1 in the cortex of the kidney. This expression reached a maximum at 24 hours and declined at 48 hours. The ICAM-1 protein expression in the preserved kidney cortex was increased at 4 hours (1.68+/-0.60 fold of control kidneys, (p=0.06)), 12 hours (2.38+/-0.90 fold, (p=0.02)), 24 hours (3.70+/-1.29 fold, (p=0.01)), and 48 hours (2.00+/-0.54 fold, (p=0.01)). The mRNA expression (the ratio of ICAM-1/GAPDH) in preserved kidneys cortex relative to control kidneys was increased at 4 hours (1.19+/-0.14 fold of control kidneys), 12 hours (1.38+/-0.16 fold),24 hours (1.77+/-0.29 fold), and 48 hours (1.19+/-0.12 fold) (p<0.05 for all time points). CONCLUSION: We conclude that cold preservation of rat kidneys in UW solution induces increasing levels of ICAM-1 cell surface expression and gene transcription. This increase in adhesion molecule expression can be a contributing factor in the development of post-transplant renal dysfunction by increasing the immunogenicity of the graft.
Animals ; Baths ; Blotting, Western ; Capillaries ; Cold Ischemia ; Humans ; Immunohistochemistry ; Intercellular Adhesion Molecule-1* ; Ischemia ; Kidney Cortex ; Kidney Transplantation ; Kidney* ; Male ; Rats* ; RNA, Messenger ; Transplants ; Wisconsin

BACKGROUND: The purpose of this study was to assess the effect of our new video-assisted asthma education program on patients' knowledge regarding asthma and asthma control. METHODS: Adult asthmatics who were diagnosed by primary care physicians and followed for at least 1 year were educated via smart devices and pamphlets. The education sessions were carried out three times at 2-week intervals. Each education period lasted at most 5 minutes. The effectiveness was then evaluated using questionnaires and an asthma control test (ACT). RESULTS: The study enrolled 144 patients (mean age, 56.7±16.7 years). Half of the patients had not been taught how to use their inhalers. After participating in the education program, the participants' understanding of asthma improved significantly across all six items of a questionnaire assessing their general knowledge of asthma. The proportion of patients who made errors while manipulating their inhalers was reduced to less than 10%. The ACT score increased from 16.6±4.6 to 20.0±3.9 (p<0.001). The number of asthmatics whose ACT score was at least 20 increased from 45 (33.3%) to 93 (65.3%) (p<0.001). The magnitude of improvement in the ACT score did not differ between patients who received an education session at least three times within 1 year and those who had not. The majority of patients agreed to the need for an education program (95.8%) and showed a willingness to pay an additional cost for the education (81.9%). CONCLUSION: This study indicated that our newly developed education program would become an effective component of asthma management in primary care clinics.
Adult ; Asthma* ; Education* ; Humans ; Nebulizers and Vaporizers ; Pamphlets ; Physicians, Primary Care ; Primary Health Care*