PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Team solves birth and migration mysteries of cortex's powerful inhibitors, 'chandelier' cells

They show how embryonic origin and timing influence cell specification and network integration

2012-11-23
(Press-News.org) Cold Spring Harbor, NY -- The cerebral cortex of the human brain has been called "the crowning achievement of evolution." Ironically, it is so complex that even our greatest minds and most sophisticated science are only now beginning to understand how it organizes itself in early development, and how its many cell types function together as circuits.

A major step toward this great goal in neuroscience has been taken by a team led by Professor Z. Josh Huang, Ph.D., at Cold Spring Harbor Laboratory (CSHL). Today they publish research for the first time revealing the birth timing and embryonic origin of a critical class of inhibitory brain cells called chandelier cells, and tracing the specific paths they take during early development into the cerebral cortex of the mouse brain.

These temporal and spatial sequences are regarded by Huang as genetically programmed aspects of brain development, accounting for aspects of the brain that are likely identical in every member of a given species including humans. Exceptions to these stereotypical patterns include irregularities caused by gene mutations or protein malfunctions, both of which are now being identified in people with developmental disorders and neuropsychiatric illnesses.

Chandelier cells were first noticed only 40 years ago, and in the intervening years frustratingly little has been learned about them, beyond the fact that they "hang" individually among great crowds of excitatory cells in the cortex called pyramidal neurons, and that their relatively short branches make contact with these excitatory cells. Indeed, a single chandelier cell connects, or "synapses," with as many as 500 pyramidal neurons. Noting this, the great biologist Francis Crick decades ago speculated that chandelier cells exerted some kind of "veto" power over the messages being exchanged by the much more numerous excitatory cells in their vicinity.

Born in a previously undiscovered 'country'

After three years of painstaking work that has involved using new technologies to identify and trace neural cell progenitors in ways not previously possible, and to track them as they migrate to positions in the maturing cortex, Huang and colleagues, including Dr. Hiroki Taniguchi now at the Max Planck Florida Institute, have demonstrated that chandelier cells are born in a previously unrecognized portion of the embryonic brain, which they have named the VGZ (ventral germinal zone).

Huang, who has been on a decade-long quest to develop means of learning much more about the cortex's inhibitory cells (sometimes called "interneurons"), points out that while they are far less numerous than the excitatory pyramidal cells all around them, cells including chandelier cells that inhibit or modulate excitatory-cell messages play an indispensable role in balancing message flow and ultimately in determining the functional organization of excitatory neurons into meaningful groups.

This is all the more intriguing in the case of chandelier cells, Huang explains, because of their distinctive anatomy: one cell that can regulate the messages of 500 others in its vicinity is one that we need to know about if we want to understand how brain circuits work. Unlike other inhibitory cells, chandelier cells are known to connect with excitatory cells at one particular anatomical location, of great significance: a place called the axon initial segment (AIS) – the spot where a "broadcasting" pyramidal cell generates its transmittable message. To be able to interdict 500 "broadcasters" at this point renders a single chandelier cell a very important player in message propagation and coordination within its locality.

Because of the strategic importance of such cells throughout the cortex, it has been a source of frustration to neuroscientists that they (and other inhibitory cells) have been difficult to classify. Huang has pursued a strategy of following them from their places of birth in the emerging cortex.

Many inhibitory cells come from a large incubator area called the MGE (medial ganglionic eminence); until now, it was not known that most chandelier cells are not born there, and indeed do not emerge until after the MGE has disappeared. Only at this point does the much smaller VGZ form, providing a place where neural precursor cells specifically give rise to chandelier cells.

The team learned that manufacture of a protein encoded by a gene called Nkx2.1 is among the signals marking the birth of a chandelier cell. The gene's action, they found, is also necessary to make the cells. Nkx2.1is a transcription factor, whose expression has previously been linked to the birth of other inhibitory neuronal types. Huang's team observes that it is the timing of Nkx2.1's expression in certain precursors -- following disappearance of the MGE and appearance of the VGZ -- that enabled them to track the birth, specifically, of chandelier cells.

Highly specific migration route and cortical destinations

"In addition to being surprised to discover that chandelier cells are born 'late'—after other inhibitory cells – in a part of the cortex we didn't know about," says Huang, "our second surprise is that once born, these cells take a very stereotyped route into the cortex and assume very specific positions, in three cortical layers." (Layers 2, 5 and 6). "This leads us to postulate that other specific cortical cell types also have specific migration routes in development."

As Huang points out, his team's new discoveries about chandelier cells have implications for disease research, since it is known that the number and connective density of chandelier cells is diminished in schizophrenia. Associations of the same type have recently been made in epilepsy.

"To know the identity of a cell type in the cortex is in effect to know the intrinsic program that distinguishes it from other cell types. In the broadest terms, we are learning about those aspects of the brain development that make us human. 'Nurture,' or experience, also has a very important role in brain development. Our work helps clarify the 'nature' part of the nature/nurture mystery that has always fascinated us," Huang says.

### "The spatial and temporal origin of chandelier cells in mouse cortex" appears online ahead of print November 22, 2012 in Science Express. Publication in Science is scheduled for December 14, 2012. The authors are: Hiroki Taniguchi, Jiangteng Lu and Z. Josh Huang. The paper will be available on the Science Express website at 2 pm EST Nov. 22, 2012. http://www.sciencemag.org/content/early/recent

This research was supported by National Institutes of Health grant R01 MH094705. Other support came from the Japan Science and Technology Agency, NARSAD/The Brian and Behavior Research Foundation; The Patterson Foundation; The Simons Foundation; The Robertson Neuroscience Fund at CSHL.

About Cold Spring Harbor Laboratory Founded in 1890, Cold Spring Harbor Laboratory (CSHL) has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. CSHL is ranked number one in the world by Thomson Reuters for impact of its research in molecular biology and genetics. The Laboratory has been home to eight Nobel Prize winners. Today, CSHL's multidisciplinary scientific community is more than 360 scientists strong and its Meetings & Courses program hosts more than 12,500 scientists from around the world each year to its Long Island campus and its China center. Tens of thousands more benefit from the research, reviews, and ideas published in journals and books distributed internationally by CSHL Press. The Laboratory's education arm also includes a graduate school and programs for undergraduates as well as middle and high school students and teachers. CSHL is a private, not-for-profit institution on the north shore of Long Island. For more information, visit www.cshl.edu.


ELSE PRESS RELEASES FROM THIS DATE:

Scripps Research Institute scientists describe elusive replication machinery of flu viruses

Scripps Research Institute scientists describe elusive replication machinery of flu viruses
2012-11-23
LA JOLLA, CA – November 22, 2012 – Scientists at The Scripps Research Institute (TSRI) have made a major advance in understanding how flu viruses replicate within infected cells. The researchers used cutting-edge molecular biology and electron-microscopy techniques to "see" one of influenza's essential protein complexes in unprecedented detail. The images generated in the study show flu virus proteins in the act of self-replication, highlighting the virus's vulnerabilities that are sure to be of interest to drug developers. The report, which appears online in Science ...

Star Trek Classroom: The next generation of school desks

Star Trek Classroom: The next generation of school desks
2012-11-23
Researchers designing and testing the 'classroom of the future' have found that multi-touch, multi-user desks can boost skills in mathematics. New results from a 3-year project working with over 400 pupils, mostly 8-10 year olds, show that collaborative learning increases both fluency and flexibility in maths. It also shows that using an interactive 'smart' desk can have benefits over doing mathematics on paper. Using multi-touch desks in the new classroom, the children were able to work together in new ways to solve and answer questions and problems using inventive ...

Le Rouge et le Noir: Where the black dahlia gets its color

Le Rouge et le Noir: Where the black dahlia gets its color
2012-11-23
The molecular mechanisms whereby a spectrum of dahlias, from white to yellow to red to purple, get their colour are already well known, but the black dahlia has hitherto remained a mystery. Now, a study published in BioMed Central's open-access journal BMC Plant Biology reveals for the first time that the distinctive black-red colouring is based on an increased accumulation of anthocyanins as a result of drastically reduced concentrations of flavones. Dahlia variabilis hort. is a popular garden flower. Continuous dahlia breeding worldwide has led to the availability of ...

Magnesium oxide: From Earth to super-Earth

2012-11-23
Washington, D.C.— The mantles of Earth and other rocky planets are rich in magnesium and oxygen. Due to its simplicity, the mineral magnesium oxide is a good model for studying the nature of planetary interiors. New work from a team led by Carnegie's Stewart McWilliams studied how magnesium oxide behaves under the extreme conditions deep within planets and found evidence that alters our understanding of planetary evolution. It is published November 22 by Science Express. Magnesium oxide is particularly resistant to changes when under intense pressures and temperatures. ...

JSC Products Announces Launch of New Humorous "Junior Senior Citizen" Clothing Line

2012-11-23
New firm specializes in senior humor apparel and products geared toward senior citizen humor. Las Vegas - JSC Products today announced the launch of their Junior Senior Citizen clothing line. The Las Vegas-based firm has an initial offering of men's and women's t-shirts, and plans to roll out other products in the coming months. "Age is a state of mind," says Stacey Ranieri, founder and brand creator for JSC Products. "We are vibrant, productive, virile citizens who are just getting older, but aren't ready to call ourselves old. Our new line of clothing ...

Emil's Sausage Kitchen Inc. Wins Three Consecutive Talk of the Town Awards for Customer Satisfaction

2012-11-23
With a jump in its ratings during the past three years from 4 stars to 5 stars, Emil's Sausage Kitchen Inc. has earned its third straight CMUS Talk of the Town Customer Satisfaction Award in the Food — European Deli category. The Talk of the Town Awards, presented by Talk of the Town News, Customer Care News magazine and Celebration Media U.S. (CMUS), honors companies and professionals that provide excellent customer service as reported by their customers through no-cost, user-review websites, blogs, social networks, business rating services, and other honors and accolades. ...

Online Book Launch: What if the Problem's Not the Problem???

2012-11-23
In What if the Problem's Not the Problem??? Jasmyne reveals the simple truth about what it takes to feel free and at peace in your every day life. The book offers four practices that will bring you a sense of well-being that won't waver no matter what your outer circumstances look like. The transformative teachings and relatable stories, inquiries and exercises can be applied to every day challenges, both big and small, including relationship frustrations, losing a job, raising children and even the death of a loved one. They are profoundly simple and easily assimilated, ...

Author Loretta Wade Releases First Non-Fiction Novel "Single Handed - The Story of Keith Maze and His Dog Wishbone"

2012-11-23
The D.B. Myers Co. announces the publication and release of "Single Handed - The Story of Keith Maze and His Dog Wishbone" By author Loretta Wade. This is a heartwarming story of how an Alabama family's struggle to overcome adversity turns into victory. The book is centered around Keith Maze and his battle with epithelioid sarcoma. This deadly cancer causes Keith to lose his right hand after several failed surgeries. During Keith's ordeal, his dog Wishbone gets into a terrible accident and eventually loses a front leg. Ironically, Keith and his dog Wishbone ...

Chapel Hill To Host Open House On Nov. 25

2012-11-23
Chapel Hill Retirement Community in Canal Fulton, Ohio, will host an open house on Sunday, Nov. 25, from 1-3 p.m. Visitors will be able to tour Chapel Hill's cottages and sample its cuisine. Staff will be available to answer any questions. "Our open house is a great opportunity to explore retirement options and enjoy some delicious food and partake in a free giveaway," says Administrator Susan Strutner. "Prepare to be surprised!" Attendees will discover firsthand how Chapel Hill is taking health care in a new direction with its roomy two-bedroom ...

John M. Collard Named Chairman of the Association of Interim Executives. New Association Launched to Promote Expertise.

2012-11-23
Interim executives wage a covert war against corporate inefficiency and underperformance. Today's launch of the Association of Interim Executives http://www.interimexecs.org marks a new day for interim executives and the companies that need them. Go ahead and think of an interim exec as the James Bond of the executive suite: a nimble operator who brings the precise tools to get the job done. Now, an association has his back. The association's select membership includes champion business leaders who've already been doing the behind-the-scenes engagements, empowering ...

LAST 30 PRESS RELEASES:

New study finds mechanical valves offer superior long-term survival for aortic valve replacement patients aged 60 and younger

Anatomic lung resection linked to improved survival for early-stage lung cancer

Combination of dual-targeted therapies and chemotherapy shows high response rates in BRAF-mutated metastatic colorectal cancer

Blood test could guide use of anti-inflammatory drug celecoxib to reduce risk of colon cancer recurrence

Blood test from Alliance trial guides use of anti-inflammatory drug to lower colon cancer recurrence risk

New dyes pave way for better photothermal cancer treatment and diagnosis

New drug shows promise in restoring vision for people with nerve damage

Scientists discover unique microbes in Amazonian peatlands that could influence climate change

University Hospitals now offering ultra-minimally invasive endoscopic spine surgery for patients experiencing back pain

JNM publishes procedure standard/practice guideline for fibroblast activation protein PET

What to do with aging solar panels?

Scientists design peptides to enhance drug efficacy

Collaboration to develop sorghum hybrids to reduce synthetic fertilizer use and farmer costs

Light-activated ink developed to remotely control cardiac tissue to repair the heart

EMBARGOED: Dana-Farber investigators pinpoint keys to cell therapy response for leukemia

Surgeon preference factors into survival outcomes analyses for multi- and single-arterial bypass grafting

Study points to South America – not Mexico – as birthplace of Irish potato famine pathogen

VR subway experiment highlights role of sound in disrupting balance for people with inner ear disorder

Evolution without sex: How mites have survived for millions of years

U. of I. team develops weight loss app that tracks fiber, protein content in meals

Progress and challenges in brain implants

City-level sugar-sweetened beverage taxes and changes in adult BMI

Duration in immigration detention and health harms

COVID-19 pandemic and racial and ethnic disparities in long-term nursing home stay or death following hospital discharge

Specific types of liver immune cells are required to deal with injury

How human activity has shaped Brazil Nut forests’ past and future

Doctors test a new way to help people quit fentanyl 

Long read sequencing reveals more genetic information while cutting time and cost of rare disease diagnoses

AAAS and ASU launch mission-driven collaborative to strengthen scientific enterprise

Medicaid-insured heart transplant patients face higher risk of post-transplant complications

[Press-News.org] Team solves birth and migration mysteries of cortex's powerful inhibitors, 'chandelier' cells
They show how embryonic origin and timing influence cell specification and network integration