Midbrain dopamine seems to play an outsized role in motivated behavior and learning. Widely associated with mediating reward-related behavior, decision making, and learning, dopamine continues to generate controversies in the field. While many studies and theories focus on what dopamine cells encode, the question of how the midbrain derives the information it encodes is poorly understood and comparatively less addressed.
View Article and Find Full Text PDFJ Neurol Neurosurg Psychiatry
November 2018
Movement disorders arise from the complex interplay of multiple changes to neural circuits. Successful treatments for these disorders could interact with these complex changes in myriad ways, and as a consequence their mechanisms of action and their amelioration of symptoms are incompletely understood. Using Parkinson's disease as a case study, we review here how computational models are a crucial tool for taming this complexity, across causative mechanisms, consequent neural dynamics and treatments.
View Article and Find Full Text PDFThe bradykinesia and other motor signs of Parkinson's disease (PD) are linked to progressive loss of substantia nigra dopamine (DA) neurons innervating the striatum. However, the emergence of idiopathic PD is likely preceded by a prolonged subclinical phase, which may be masked by a variety of pre- and postsynaptic compensatory mechanisms. It is often considered self-evident that the signs of PD manifest only when nigrostriatal degeneration has proceeded to such an extent that putative compensatory mechanisms fail to accommodate the depletion of striatal DA levels.
View Article and Find Full Text PDFOptogenetics is an emergent technology that combines light-sensitive proteins derived from algae, so-called opsins, with genetics. Viral vectors encoding opsins are injected into selective brain regions whereby specific cell populations can be controlled with high precision light pulses delivered via implanted optical fibres. This review focuses on explaining basic principles of optogenetics and describes important insights into neuropsychiatric mechanisms provided by the technology.
View Article and Find Full Text PDFDopamine (DA) D2-like autoreceptors are an important component of the DA system, but their influence on postsynaptic DA signaling is not well understood. They are, directly or indirectly, involved in drug abuse and in treatment of schizophrenia and attention deficit hyperactive disorder: DA autoreceptors influence the behavioral effect of cocaine and methylphenidate and may be the target of antipsychotic medications such as haloperidol. DA autoreceptors are active at two levels: Somatodendritic autoreceptors mainly influence firing rate of DA neurons, and presynaptic autoreceptors control release of neurotransmitter at axonal terminals.
View Article and Find Full Text PDFFunctionalized polymer nanoparticles are used as binders for inorganic materials in everyday technologies such as paper and coatings. However, the functionalization can give rise to two opposing effects: It can promote adhesion via specific interactions to the substrate, but a high degree of functionalization can also hamper spreading on substrates. Here, we studied the spreading kinetics of individual functionalized vinyl acetate-co-ethylene polymer nanoparticles on inorganic substrates by atomic force microscopy (AFM) imaging.
View Article and Find Full Text PDFJ Aerosol Med Pulm Drug Deliv
December 2009
Background: Mass-weighted aerodynamic particle-size distribution (APSD) is a key attribute for pharmaceutical products developed to deliver drugs to or through the lungs. In development and quality control, APSD is primarily determined using multistage cascade impactors. For impactor techniques, particle reentrainment is critical because it may lead to an overestimation of the respirable fraction.
View Article and Find Full Text PDFPhys Rev E Stat Nonlin Soft Matter Phys
May 2006
In a nanoscale system out of thermodynamic equilibrium, it is important to account for thermal fluctuations. Typically, the thermal noise contributes fluctuations, e.g.
View Article and Find Full Text PDFWe present an experimental method based on video microscopy to perform nanometer scale position detection of a micrometer bead in the direction along the propagation of the detection light. Using the same bead for calibration and detection significantly improves the in depth resolution in comparison to video microscopy methods from literature. This method is used together with an optical trap to measure interaction potentials between a glass surface and colloids made of polystyrene or silica at different electrolyte concentrations.
View Article and Find Full Text PDFWe investigate the axial position detection of a trapped microsphere in an optical trap by using a quadrant photodiode. By replacing the photodiode with a CCD camera, we obtain detailed information on the light scattered by the microsphere. The correlation of the interference pattern with the axial position displays complex behavior with regions of positive and negative interference.
View Article and Find Full Text PDFUsing optical tweezers and single particle tracking, we have revealed the motion of a single protein, the lambda-receptor, in the outer membrane of living Escherichia coli bacteria. We genetically modified the lambda-receptor placing a biotin on an extracellular site of the receptor in vivo. The efficiency of this in vivo biotinylation is very low, thus enabling the attachment of a streptavidin-coated bead binding specifically to a single biotinylated lambda-receptor.
View Article and Find Full Text PDF