Fast-spiking interneurons and the critical period

How do children learn to play instruments and speak languages so much easier than adults, and why does brain damage result in worse outcomes in the mature brain vs. the young brain?  These questions are central to the study of how “critical periods” are regulated in the brain.

fs-interneuron

Electron micrograph from a single 70 nm cross-section through a fast-spiking parvalbumin-containing (gold labeling = white dots) presynaptic terminal forming a synapse (red dots) with a pyramidal soma. Original colors are inverted, contours have been raised and membranous structures are highlighted in aqua for ease of visualization. Presynaptic vesicles (colored ovals) within perisomatic fast spiking terminals mostly cluster within ∼200 nm of the synapse, with a few close enough (≤2 nm) to be deemed docked.

Critical periods in brain development define temporal windows when neuronal physiology and anatomy are most sensitive to changes in sensory input or experience (e.g. sound, touch, light, etc.).  The maturation of inhibitory cells that release the neurotransmitter GABA, especially a subset called fast-spiking (FS) interneurons, is thought to gate this period of neuronal ‘plasticity’ in the mammalian primary visual cortex.  However, it has remained unclear what aspects of FS cell development are important for permitting this period of neuronal malleability in the visual cortex. A new paper in Journal of Neuroscience from the Turrigiano lab addresses the question.

To explore how FS cell development might be linked to critical period plasticity, Brandeis postdoc Marc Nahmani and Professor Gina Turrigiano employed a well-established assay for cortical plasticity in visual cortex called monocular deprivation (MD), and measured FS cell connections using confocal and electron microscopy, as well as optogenetic stimulation of the FS cell population (i.e. shining light onto FS cells possessing light-gated channels to make them fire action potentials).

Following up on previous work from the Turrigiano lab (Maffei et al., 2006), they found that MD induces a coordinated increase in FS interneuron to pyramidal cell (the major excitatory output cells of the cortex) pre- and postsynaptic strength.  These changes occur if MD is performed during, but not before the critical period in visual cortex, suggesting they may play a role in gating this period of heightened neuronal plasticity.  Future studies are aimed at determining the timeline for these changes across the extent of the critical period in visual cortex.

see: Nahmani M, Turrigiano GG (2014) Deprivation-Induced Strengthening of Presynaptic and Postsynaptic Inhibitory Transmission in Layer 4 of Visual Cortex during the Critical Period. Journal of Neuroscience 34:2571-2582.

4th Annual Sprout Grants – Call for applications

Bring your research and entrepreneurial ambitions to life!

The Brandeis University Virtual Incubator invites member of the Brandeis Community (undergrads, grad students, postdoctoral fellows, faculty, staff) to submit an application for a “Sprout Grant”. These grants are intended to stimulate entrepreneurship on campus and help researchers launch their ideas and inventions from Brandeis to the marketplace.

This spring we will be awarding $50,000 to be shared amongst the most promising proposals.

Come get your questions about the Sprout grant answered at one of our upcoming information sessions.

Info sessions:

Tuesday      February 18th    1pm – 2pm

Tuesday      February 25th    10am – 11am

Thursday     February 27th    11am – noon

Tuesday      March 4th          11am – noon

All information sessions will be held in the Shapiro science center 1st floor library, room 1-03 (the glass walled room near the elevators).

Deadlines: Preliminary applications are due on Friday, March 7th

Benefits of participation:

  • Teams that are selected to submit full applications will be given assistance in further developing their ideas into an effective business pitch.
  • Sprout grant winners will be connected with an experienced mentor, and given further assistance in getting their ideas to market by the Office of Technology Licensing.
  • Previous winners have come from many departments: Neuroscience, Biology, Biochemistry, Physics and Computer Science. Some of the funded technologies have resulted in patent applications and are moving towards commercial development. Read more about previous winners from your department here: Sprout winners 2011, Sprout winners 2012, Sprout winners 2013.

For more information go to our website (http://www.brandeis.edu/otl/grants/index.html) or contact Melissa Blackman at melblack@brandeis.edu.

Can Self-Referencing Contribute to Memory Errors?

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.

How bacteria resist fluoride

Fluoride anion is everywhere.  Released into water through the natural weathering of rocks, it’s present to the tune of 5 mM in toothpaste, 30 μM in Cape Cod bay, and 17 μM in Massell pond at Brandeis.

Fluoride levels in our environment (graph).001

Fluoride in the environment, measurements by Ashley Brammer (Miller lab)

Since F is ancient, ubiquitous and toxic to microbes, it’s not surprising that bacteria have evolved defenses to expel it from their cytoplasm.   In an article published in eLife on August 27, 2013, Randy Stockbridge, Janice Robertson, and Luci Partensky from Chris Miller’s lab describe one of these microbial defenses, a fluoride channel called Fluc.  The channel provides a pathway for F to exit the cell across the membrane at a rate of 107 ions per second, while rigorously excluding Cl in order to avoid catastrophic membrane depolarization. The world-record 10,000-fold selectivity isn’t the only remarkable aspect of Fluc, however. The Fluc channel is built on an antiparallel dimer scaffold, with one of the subunits facing the exterior of the cell, and the other facing the interior. Only one other modern-day membrane protein is known to dimerize like this, but the arrangement recalls the inverted structural repeats that are a common, important motif for membrane transporters. Inverted repeats are the product of an antiparallel dimer, like Fluc, that duplicated and fused eons ago.  The sequences drifted over time until the duplication was undetectable by sequence similarity, and the plethora of membrane transport proteins built on this plan was only discovered when the 3-D structures were solved. The Fluc family provides the opportunity to study microorganism resistance to an ancient xenobiotic, as well as membrane protein architecture from an evolutionary origin.

For more, you should read the paper:

Stockbridge RB, Robertson JL, Kolmakova-Partensky L, Miller C. A family of fluoride-specific ion channels with dual-topology architecture. eLife. 2013;2(0):e01084. PMCID: 3755343.

PS: If you’re wondering about the tea on the bar graph, tea plants accumulate F in their leaves.  Cheap teas, made from older tea leaves, actually carry a lot of F, and if you drink a couple quarts of lousy tea a day, you can give yourself skeletal fluorosis.

Marder lab researchers win best paper contest

Alex Williams and Timothy O’Leary from the Marder Lab have won first place in the 2012  Brain Corporation Prize Competition in Computational Neuroscience  for their Scholarpedia article Homeostatic Regulation of Neuronal Excitability.  Williams, a Bowdoin College graduate currently working as post-baccalaureate research technician at Brandeis, and O’Leary, a postdoctoral fellow, won the worldwide competition to write the most popular review in the area of computational neuroscience, and gained a $5,000 prize, a feat that required not only superb writing but also mobilizing the audience to vote for paper. The award ceremony is today at the Computational Neuroscience (CNS’13) meeting in Paris.

Check out the winning entry online.

Summer Seminars Start on the Sixth

Science is a year-round endeavor, so science seminars will continue over the seminar, though the venues and times may shift.

D-Day for summer seminars this year is June 6, when the Biochemistry & Biophysics Summer Pizza Talks series kicks off with Dr Markus Grütter of the University of Zurich. Grütter will give a special summer on his recent breakthrough-structure of the first heterodimeric ABC transporter. This structure is important because the ABC transporter is a homologue of the CFTR channel (disrupted in cystic fibrosis, one of the most common human genetic diseases). The talk will be in Gerstenzang 121 at Noon on Thursday, June 6.

The Life Sciences Summer Research Seminar Series will start on Monday, June 24, with a talk by distinguished alumna Leslie Meltzer ’03, who has returned to the Boston area as Associate Director of U.S. Medical Affairs at Biogen IDEC, having paid a visit to the other coast to get a Ph.D. in Neuroscience at Stanford in 2008, working with Karl Deisseroth. The Life Sciences Summer Research Seminar Series is organized by the Brandeis University Postdoctoral Association and will be held on Mondays at noon in Gerstenzang 121.

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