A recent paper in the Journal of Gerontology by Brandeis Ph.D. program alumnus Dr. Nicole Rosa and Professor Angela Gutchess attempts to answer this question. During an interview with ElderBranch, Dr. Nicole Rosa discusses the relationship between self-referencing and false memory. For more information, please read the article on ElderBranch.
Rectifying electrical synapses are more interesting than they might seem at first. Our recent study finds that they have the potential to allow a circuit to control how robust the circuit output is to modulation of synaptic strength.
Gap junctions allow neurons to communicate quickly by serving as a direct conduit of electrical signals. Non-rectifying gap junctions probably come to mind first for most neuroscientists when they think about electrical synapses, since they are the idealized textbook variety. The electrical current that passes through the non-rectifying type of gap junction is simply a function of the voltage difference between the coupled neurons. However, this is only the case when the two hemi-channels that form a gap junction pore have the same voltage-dependencies.
We know from past electrophysiology studies that a single neuron can express a diverse set of gap junction hemi-channels, enabling it to form similarly diverse gap junction channels with another neuron. This could result in rectifying electrical synapses in which current flows asymmetrically between neurons so that current flow can either be permitted or restricted depending on whether the current is positive or negative. What we didn’t know were the consequences of electrical synapse rectification for a pattern-generating circuit of competing oscillators. Our recently published study in J. Neuroscience addressed this question and led us to conclude that rectifying electrical synapses can change how a neuronal circuit responds to modulation of its synapses – including its chemical synapses. Although we used a computational model for our study, our results indicate that rectifying electrical synapses in biological networks can be an important component in neuronal circuits that produce rhythmic patterns, such as those found in motor systems.
Gabrielle Gutierrez obtained her PhD in Neuroscience from Brandeis earlier this year, and is currently doing a postdoc with Sophie Deneuve at the Ecole Normale Superieure in Paris
Gutierrez GJ, Marder E. Rectifying electrical synapses can affect the influence of synaptic modulation on output pattern robustness. J Neurosci. 2013;33(32):13238-48.
Between vacation and some busy weeks at work, we didn’t get much of a chance to post stuff about new science from Brandeis. To make up for it, some stuff that we noticed in July:
[...] nef2 links the Drosophila core clock to fas2, neuronal morphology, and circadian behavior [...]: Postdoc Anna Sivachenko et al. look at the links between the circadian clock and activity-dependent neuronal remodeling (Rosbash lab)
The insulin receptor cellular IRES confers resistance to eIF4A inhibition: MCB grad students Calla Olson, Marissan Donovan, and Mike Spellberg look at how translation of the insulin receptors is controlled during times of stress. (Marr lab) [story at BrandeisNOW]
The annual summer meeting of Sloan-Swartz Centers for Computational Neuroscience will be held at Brandeis this weekend (July 26-28). Neuroscientists from centers at 11 major US educational institutions will convene to talk about research progress from the last year. Talks by professors, postdocs, and grad students will be held Friday through Sunday in the Shapiro Campus Center Auditorium – the schedule is online. The poster session, including posters from Brandeis undergraduates and grad students, will be held on Friday evening. All welcome to attend talks. Food available for those who have preregistered.
To utilize the information contained within a cell’s genes, the enzyme RNA polymerase must find the beginning of each gene (the promoter). Finding the beginning is a prodigious task: RNAP must start at a particular base pair of DNA, but the cell contains millions of base pairs to choose from. It has been proposed that gene-finding challenge is aided by a process termed ‘facilitated diffusion’ (FD). In FD, RNA polymerase first binds to a random position on DNA and then slides along the DNA like a bead on a string until it encounters the target DNA sequence.
In a recently published study in PNAS (1), biophysicists Larry Friedman and Jeffrey Mumm worked with Prof. Jeff Gelles in the Brandeis Biochemistry department to test key predictions of the FD model. They used a novel light microscope that Friedman and colleagues invented and built at Brandeis, a microscope that can directly observe the binding of an individual RNA polymerase to a single DNA. The scientists studied the σ54 RNA polymerase holoenzyme, an RNA polymerase found in most species of bacteria. Surprisingly, none of the three predictions of the FD model that the experiments tested were found to be valid, demonstrating that target finding by the polymerase is not accelerated by sliding along DNA. Friedman and colleagues instead propose that RNA polymerases are present in such large numbers that they can diffuse through the cell and efficiently bind to their target sites directly. The absence of FD may explain how other proteins can bind to positions on the DNA that flank gene start sites and yet not interfere with RNA polymerase finding the gene.
Is this the end of the story? Not likely, given previous publications suggesting FD plays a role for some other DNA binding proteins. Using single-molecule techniques like those developed in the Gelles lab, scientists in next few years should give us a better idea if FD is very rare or very common. [editor: as a chemical engineer, I'm sad to see FD not have a role -- it seemed like such a nice theory...]
Friedman LJ, Mumm JP, Gelles J. RNA polymerase approaches its promoter without long-range sliding along DNA. Proc Natl Acad Sci U S A. 2013 May 29. [Epub ahead of print]
There are two main types of synaptic connections in the mammalian brain: excitatory glutamatergic synapses and inhibitory GABAergic synapses. The balance between excitatory and inhibitory inputs a neuron receives regulates the overall activity of neuronal networks; disruptions to this balance can cause epilepsy.
A new paper in J. Neuroscience from the Paradis lab shows that treatment of cultured neurons with the extracellular domain of the protein Sema4D causes a rapid increase (i.e. within 30 minutes) in the density of functional GABAergic synapses. Further, addition of Sema4D to neurons drives GABAergic synapse formation through a previously unappreciated mechanism: the splitting of pre-existing assemblies of the Gephyrin scaffolding protein. To our knowledge this is the fastest demonstration of synapse formation reported thus far and has significant implications for our understanding of the mechanisms of GABAergic synapse formation.
While the underlying mechanism of epileptogenesis is largely unknown, recurrent seizures emerge when there is an increase in network activity. One possible therapeutic treatment would be to restore normal network activity by increasing network inhibition. In an in vitro model of epilepsy, acute treatment with the protein Sema4D rapidly silences neuronal hyperexcitability, suggesting a possible use of Sema4D as a disease-modifying treatment for epilepsy.
Lead authors on the paper were Marissa Kuzirian, a grad student in the Neuroscience Ph.D. program, and Anna Moore, a Brandeis Neuroscience postdoctoral fellow.
We’ve all been busy this spring writing grants and teaching courses and doing research and graduating(!), so lots of publications snuck by that we didn’t comment on. Here’s a few I think that might be interesting to our readers.
- From Chris Miller‘s lab, bacterial antiporters do act as “virtual proton efflux pumps”:
- Tsai MF, Miller C. Substrate selectivity in arginine-dependent acid resistance in enteric bacteria. Proc Natl Acad Sci U S A. 2013;110(15):5893-7.
- Tsai MF, McCarthy P, Miller C. Substrate selectivity in glutamate-dependent acid resistance in enteric bacteria. Proc Natl Acad Sci U S A. 2013;110(15):5898-902.
- Are ninja stars responsible for controlling actin disassembly? Seems like the Goode lab might think so.
- Chaudhry F, Breitsprecher D, Little K, Sharov G, Sokolova O, Goode BL. Srv2/cyclase-associated protein forms hexameric shurikens that directly catalyze actin filament severing by cofilin. Mol Biol Cell. 2013;24(1):31-41.
- What do you get from statistical mechanics of self-propelled particles? The Hagan and Baskaran groups team up to find out.
- Redner GS, Hagan MF, Baskaran A. Structure and dynamics of a phase-separating active colloidal fluid. Phys Rev Lett. 2013;110(5):055701.
- From John Lisman and Ole Jensen (PhD ’98), thoughts about what the theta and gamma rhythms in the brain encode
- Lisman JE, Jensen O. The theta-gamma neural code. Neuron. 2013;77(6):1002-16.
- From Mike Marr‘s lab, studeies using genome-wide nascent sequencing to understand how transcrption bursting is controlled in eukaryotic cells
- Pennington KL, Marr SK, Chirn GW, Marr MT, 2nd. Holo-TFIID controls the magnitude of a transcription burst and fine-tuning of transcription. Proc Natl Acad Sci U S A. 2013;110(19):7678-83.
- From the Lau and Sengupta labs, RNAi pathways contribute to long term plasticity in worms that have gone through the Dauer stage
- Hall SE, Chirn GW, Lau NC, Sengupta P. RNAi pathways contribute to developmental history-dependent phenotypic plasticity in C. elegans. RNA. 2013;19(3):306-19.
- Can nanofibers selectively disrupt cancer cell types? Early results from Bing Xu‘s group.
- Kuang Y, Xu B. Disruption of the Dynamics of Microtubules and Selective Inhibition of Glioblastoma Cells by Nanofibers of Small Hydrophobic Molecules. Angew Chem Int Ed Engl. 2013.
The ‘Insight Awards‘ is a video contest showcasing research imagery from the physical and life sciences which utilize Andor technology to capture data. This year, the Dogic Lab submitted a research video to the competition and garnered first prize in the Physical Sciences division for their video of Oscillating Microtubule Bundles.
From the competition notes:
Microtubules are a bio-polymer composed of the protein tubulin and are used extensively in the cell for cellular division, cell motility, and transportation of cargo within the cell. Here, we investigate the material properties of mixtures of microtubules, a depletion agent, and the molecular motor Kinesin. The microtubules, driven by Kinesin motors, spontaneously organize into bundles of microtubules that oscillate in a manner reminiscent of flagella and cilia found in biology. This engineered system will allow us to studying systems of self-propelled and self-organized matter that exist far from equilibrium in the field known as Active Matter.
We use standard fluorescent microscopy to image labeled microtubules in a thin, flow cell microscope chamber. An Andor Clara camera was used in conjunction with a Nikon Ti Eclipse microscope to capture this video.
Video and Entry by Stephen DeCamp.