48 research outputs found
Leptin Promotes Striatal Dopamine Release via Cholinergic Interneurons and Regionally Distinct Signaling Pathways
No full textDopamine (DA) is a critical regulator of striatal network activity and is essential for motor activation and reward-associated behaviors. Previous work has shown that DA is influenced by the reward value of food, as well as by hormonal factors that reguate food intake and energy expenditure. Changes in striatal DA signaling also have been linked to aberrant eating patterns. Here we test the effect of leptin, an adipocyte-derived hormone involved in feeding and energy homeostasis regulation, on striatal DA release and uptake. Immunohistochemical evaluation identified leptin receptor (LepR) expression throughout mouse striatum, including on striatal cholinergic interneurons (ChIs) and their extensive processes. Using fast-scan cyclic voltammetry (FSCV), we found that leptin causes a concentration-dependent increase in evoked extra-cellular DA concentration ([DA]o) in dorsal striatum (dStr) and nucleus accumbens (NAc) core and shell in male mouse striatal slices, and also an increase in the rate of DA uptake. Further, we found that leptin increases ChI excitability, and that the enhancing effect of leptin on evoked [DA]o is lost when nicotinic acetylcholine (ACh) receptors are antagonized or when examined in striatal slices from mice lacking ACh synthesis. Evaluation of signaling pathways underlying leptin's action revealed a requirement for intracellular Ca2+, and the involvement of different downstream pathways in dStr and NAc core versus NAc shell. These results provide the first evidence for dynamic regulation of DA release and uptake by leptin within brain motor and reward pathways, and highlight the involvement of ChIs in this process.SIGNIFICANCE STATEMENT Given the importance of striatal dopamine (DA) in reward, motivation, motor behavior and food intake, identifying the actions of metabolic hormones on DA release in striatal subregions should provide new insight into factors that influence DA-dependent motivated behaviors. We find that one of these hormones, leptin, boosts striatal DA release through a process involving striatal cholinergic interneurons (ChIs) and nicotinic acetylcholine (ACh) receptors. Moreover, we find that the intracellular cascades downstream from leptin receptor (LepR) activation that lead to enhanced DA release differ among striatal subregions. Thus, we not only show that leptin regulates DA release, but also identify characteristics of this process that could be harnessed to alter pathologic eating behaviors
Eliminating Speckle Noises for Laser Doppler Vibrometer Based on Empirical Wavelet Transform
No full textThis paper presents a novel approach for eliminating speckle noises in Laser Doppler Vibrometer signals based on empirical wavelet transform (EWT). The moving root-mean-square thresholds are utilized to cut off signal drop-outs and produce noise discontinuity that EWT can identify. The extremum ratio behaves as the criterion to reject or accept the EWT decomposed components. While processing simulated signals, the EWT-based approach outperforms others and presents de-speckle robustness. In experiments, EWT reveals the actual vibration despite low signal-to-noise ratios, which indicates de-speckle efficiency.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Railway Engineerin
Russisch kolonel op bezoek
No full textFragment uit het boek "Den oceaan over. Reisherinneringen van B. Witkovsky", betreffende Witkovsky's bezoek aan Utrecht in 189
Activity-Dependent Phosphorylation of Tyrosine Hydroxylase in Dopaminergic Neurons of the Rat Retina
No full text
D2 dopamine receptor-mediated inhibition of a hyperpolarization-activated current in rod photoreceptors
No full text 1. Using the whole cell patch clamp method, we investigated the effect of dopamine on a hyperpolarization-activated current (Ih) in the inner segments of rod photoreceptors of the Xenopus retina. 2. Ih was elicited by hyperpolarizing voltage steps to -120 mV from a holding potential of -40 mV. Dopamine reversibly reduced Ih in a dose-dependent manner. Dopamine-mediated inhibition of Ih was blocked by the D2 dopamine antagonist sulpiride. 3. The D2 dopamine agonist quinpirole (0.1-20 microM) inhibited Ih whereas the D1 agonist SKF-38393 (100 microM) had no effect on Ih. Quinpirole-induced inhibition of Ih was blocked by sulpiride, but not by the D4 antagonist, clozapine. The D3 agonists (+/-)-7-hydroxy-2-dipropylaminotetralin hydrochloride and trans-7-hydroxy-2[N-propyl-N-(3'-iodo-2'-propenyl)amino]-tetralin maleate were, respectively, 5 and 100 times less effective than quinpirole in inhibiting Ih. 4. Quinpirole failed to reduce Ih when the internal solution contained GDP beta S (500 microM). Internal application GTP gamma S (300 microM) progressively and irreversibly reduced Ih and blocked a further reduction by quinpirole, indicating that the inhibition of Ih by quinpirole involves a G protein. 5. The inhibition of Ih by quinpirole was not affected by intracellularly applied adenosine 3',5'-cyclic monophosphate (cAMP) or by the protein kinase inhibitor H-7, indicating that a cAMP-mediated second messenger cascade does not participate in the dopamine-mediated inhibition. 6. Ih was not altered when the patch pipette contained a nominally Ca(2+)-free internal solution, but the inhibition of Ih by quinpirole was abolished, suggesting an involvement of Ca(2+) in the quinpirole-induced effect. 7. We conclude that a D2 dopamine receptor modulates Ih through the activation of a G protein and that intracellular Ca2+, but not cAMP, plays a key role in this process. 8. The reduction of Ih by dopamine may reduce the ability of rods to signal time-modulated light stimuli. </jats:p
Dependence of photoreceptor glutamate release on a dihydropyridine-sensitive calcium channel
No full textModulation of transient outward potassium current by GTP, calcium, and glutamate in horizontal cells of the Xenopus retina
No full text 1. Membrane currents of luminosity horizontal cells (L-HCs) and chromatic horizontal cells (C-HCs) isolated from the Xenopus retina were characterized using the whole-cell patch-clamp technique. 2. The current-voltage curve for the L-HC had a characteristic negative slope conductance in the voltage range of -30 to -10 mV that was not evident in the C-HC. 3. A transient outward 4-aminopyridine-sensitive potassium current (A-current) was the most prominent current in C-HCs but was also present in L-HCs. A-current characteristics in the two horizontal cell (HC) classes were closely similar. Its threshold of activation was above -45 mV. The half-voltage of inactivation was close to -70 mV. The decay of the A-current was fit by a single exponential with time constants of 30 and 40 ms at depolarizing voltage steps to -10 and +30 mV, respectively. 4. The voltage for 50% A-current inactivation shifted toward negative potentials shortly after we established the whole-cell configuration. This shift was changed to more positive potentials by internal application of guanosine 5'-triphosphate, resulting in a significant overlap of A-current activation and inactivation functions near -40 mV, which is well within the normal operating range of the HC. 5. Internal application of the G-protein activator GTP gamma S shifted the voltage-dependent inactivation of the A-current toward positive potentials by +15 mV. In contrast, GDP beta S shifted the inactivation curve by about -10 mV, similar to what was observed in untreated cells. 6. GTP and GTP gamma S increased the rate of recovery from inactivation and slowed down the rate of inactivation of the A-current enabled by a depolarizing prepulse. 7. Glutamate superfused in the bath solution significantly accelerated the rate of inactivation of A-current induced by depolarizing prepulses. The rate of A-current recovery from inactivation, however, was not affected by glutamate. 8. Removal of calcium from the bath solution reversibly decreased the amplitude of the A-current without a significant shift in its threshold of activation. </jats:p
