1. Probing Repetitive Firing in Pyramidal Neurons
Steven A. Prescott, Stéphanie Ratté, Yves De Koninck, and Terrence J. Sejnowski
In response to a continuous stimulus, some neurons slow their firing rate, an adaptation process that is mediated by slow, voltage-dependent potassium channels such as IM and IAHP. This week, Prescott et al. show that adaptation can be modulated by membrane conductance, or shunting, as occurs with background synaptic activity. In experiments and simulations, adaptation was sufficient to interrupt firing in CA1 pyramidal neurons when membrane conductance was high, but firing persisted when conductance was low. According to their model, shunting, by increasing the voltage threshold for spike generation, also enhances subthreshold activation of IM, which in turn abolishes repetitive firing. Because adaptation can minimize background spiking, the nonlinear interaction between shunting and adaptation can make for a more precise neuronal response at low firing rates by acting like a coincidence detector rather than an integrator.
2. A Well-Rounded View of the Fly Synapse
Natasha M. Viquez, Caroline R. Li, Yogesh P. Wairkar, and Aaron DiAntonio
Fly fishing in St. Louis can be quite interesting it appears. This week, Viquez et al. went fishing for regulators of the Drosophila neuromuscular junction (NMJ) and pulled out a subunit of protein phosphatase 2A (PP2A), a serine threonine phosphatase required for many cellular processes. The authors generated >2500 transposable P-element insertion lines in which the yeast upstream activating sequence promoter was randomly inserted into the fly genome. After selecting lines with altered synapse morphology, they identified four in which the P-element insertion was positioned to overexpress the gene encoding the regulatory B′ subunit of PP2A. Null mutants of the gene, dubbed well-rounded (wrd), had markedly fewer synaptic boutons and decreased synaptic strength compared with wild-type flies. Inhibition of wrd and PP2A resulted in a higher proportion of unbundled microtubules in synapses, suggesting that wrd positively regulates PP2A to stabilize the synaptic cytoskeleton.
3. Stimulus Orientation and Human Stereo Vision
Having two eyes comes in handy when gauging distances. Because each eye receives a slightly different image of an object on the retina, the disparity allows us to compute the distance to the object, as well as its position relative to nearby objects. The conventional view is that depth perception has little to do with the actual appearance of an object, but work by Farell suggests otherwise. Subjects viewed a series of visual stimuli on a computer screen consisting of a central circular patch and a surrounding ring and judged whether the central element was closer to or farther from the surrounding one. When the patterns on the two elements were in the same orientation, the observer could judge relative depth more accurately than when orientations differed. Thus, in the "real world," the orientation of textures on the surfaces of objects can affect our perception of their relative depth.
4. Mutant α-Synucleins and Cytosolic Catecholamines
Eugene V. Mosharov, Roland G. W. Staal, Jordi Bové, Delphine Prou, Anthonia Hananiya, Dmitriy Markov, Nathan Poulsen, Kristin E. Larsen, Candace M. H. Moore, Matthew D. Troyer, Robert H. Edwards, Serge Przedborski, and David Sulzer
Parkinson's disease (PD) is caused by the demise of dopamine neurons. This week, Mosharov et al. probe the role of α-synuclein, a protein mutated in some patients with PD and a major component of the telltale Lewy bodies. The authors used intracellular patch electrochemistry to specifically determine the cytosolic concentrations of catecholamines in adrenal chromaffin cells and L-DOPA-treated PC12 cells. Overexpression of wild-type or mutant α-synucleins increased cytosolic catecholamine concentrations to levels that could overwhelm the capacity of neurons to buffer against the oxyradicals produced by dopamine oxidation. Addition of α-synucleins to isolated chromaffin granules disrupted the vesicular pH gradient, indicating that the observed increase in cytosolic catecholamine resulted from the leaking of neurotransmitter from vesicles. Mutant α-synucleins produced a greater increase in cytosolic neurotransmitter than their wild-type counterpart, possibly because of their propensity to produce membrane-damaging protofibrils.
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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