Scripps Research Institute Scientists Uncover a New Pathway that Regulates Information Processing in the Brain The Study Provides New Insight into Some Types of Mental Retardation
LA JOLLA, CA November 9, 2012 Scientists at The Scripps Research Institute (TSRI) have identified a new pathway that appears to play a major role in information processing in the brain. Their research also offers insight into how imbalances in this pathway could contribute to cognitive abnormalities in humans.
The study, published in the November 9, 2012 issue of the journal Cell, focuses on the actions of a protein called HDAC4. The researchers found that HDAC4 is critically involved in regulating genes essential for communication between neurons.
We found that HDAC4 represses these genes, and its function in a given neuron is controlled by activity of other neurons forming a circuit, said TSRI Assistant Professor Anton Maximov, senior investigator for the study.
Searching for Missing Pieces
Synapses, specialized junctions that allow neurons to exchange information, are incredibly complex and built with hundreds of genes. Many of these genes become induced when neurons receive excitatory input from other neurons, including those activated by sensory experiences such as vision, hearing and smell. This process influences the assembly of neural circuits during development, and plays a fundamental role in learning and memory.
The Maximov laboratory is interested in understanding how synapses are formed and regulated. Previous studies have identified several factors necessary for activity-dependent transcription in the brain (transcription is a process of converting genetic information from DNA to RNA), but Maximov notes many puzzles remain to be solved. For example, the majority of synapse-related genes are silent in the embryonic brain, which does not receive direct sensory input from an external world. These genes become de-repressed shortly after birth, yet scientists still know little about the underlying mechanisms of how this happens.
Richard Sando III, a graduate student at the TSRI Kellogg School of Science and Technology, a member of the Maximov lab and the first author of this study, noted the team become interested in class IIa histone deacetylases (HDACs), which include HDAC4, in part because they have been implicated in regulation of transcription of non-neuronal tissues. Class IIa HDACs are also known to change their cellular localization in response to various signals, he said. There were hints that, in neurons, the translocation of HDAC4 from the nucleus to cytoplasm may be triggered by synaptic activity. We found that mutant mice lacking excitatory transmitter release in the brain accumulate HDAC4 in neuronal nuclei. But what was really exciting was our discovery that nuclear HDAC4 represses a pool of genes involved in synaptic communication and memory formation.
Coincidentally, Maximov had been familiar with these same genes since his postdoctoral training with Tomas Sudhof, a neuroscientist whose pioneering work resulted in the identification of key elements of the transmitter release machinery. It was truly astonishing when their names came up in our in vitro genome-wide mRNA profiling screens for neuronal HDAC4 targets, Maximov said.
A Link to a Rare Human Disease
To learn more about the function of HDAC4 in the brain, the team wanted to study its role in a mouse model. First, however, the scientists had to overcome a serious technical obstacle HDAC4 also appears to protect neurons from apoptosis (programmed cell death), so complete inactivation of this gene would lead to neurodegeneration. To solve this problem, the team generated mice carrying a mutant form of HDAC4 that could not be exported from the cell nucleus. This mutant repressed transcription independently of neuronal activity.
Another surprise came after the team had already initiated their experiments. Underscoring the team's findings, a human genetic study was published linking mutations in the human HDAC4 locus with a rare form of mental retardation.
One of these human mutations produces a protein similar to a mutant that we introduced into the mouse brain, said Maximov. Furthermore, our studies revealed that these mice do not learn and remember as well as normal mice, and their memory loss is associated with deficits in synaptic transmission. The pieces came together.
Most of the work in the new study was performed at TSRI's Dorris Neuroscience Center, which has state-of-the-art imaging, molecular biology and animal facilities. Here at the DNC we enjoy a terrific research environment, Maximov said. It would have been very difficult if not impossible for us to successfully perform these studies without the support of Helen Dorris and our senior colleagues who have assembled a highly productive and collaborative group of molecular neuroscientists.
Other contributors to the study, HDAC4 Governs a Transcriptional Program Essential for Synaptic Plasticity and Memory, were Natalia Gounko and Simon Pieraut from the Maximov Laboratory; John Yates III, professor in the Department of Chemical Physiology at TSRI; and Lujian Liao, a staff scientist in the Yates Laboratory.
The research was funded in part by National Institutes of Health grants MH085776, MH067880-09, RR011823, and NS057096, and by the Novartis Advanced Discovery Institute, The Baxter Foundation and the Helen Dorris Postdoctoral Fellowship.
Most recent headlines
05/01/2027
Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...
06/09/2026
June 9 2026, 23:00 (PDT) Dolby and MagentaTV Bring Fans Closer to the FIFA Worl...
04/08/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
04/07/2026
When Canada qualified for the FIFA World Cup 2026, OneSoccer knew this wasn'...
04/07/2026
Celebrates company's 80th anniversary
Rhodes have recently revealed that they will be producing a limited run of electric pianos in celebration of their...
04/07/2026
Blackmagic Design Cameras Empower Youth Broadcasting Program
Brie Clayton July 3, 2026
0 Comments
Blackmagic Pocket Cinema Camera 6K Pro and Blackmagi...
04/07/2026
iZotope Joins Boris FX
Boris Yamnitsky July 3, 2026
0 Comments
iZotope, the team behind RX and Ozone, is joining Boris FX. A letter from founder Boris...
04/07/2026
April 7 2026, 19:00 (PDT) Detective Conan: Fallen Angel of the Highway Opens in...
03/07/2026
New bundle & three Single Packs
Continuing to expand their already sizeable orchestral collection, VSL's latest release introduces three new Single Pack...
03/07/2026
Venue installs new ATC-equipped control room
LSO St Luke's, a unique music venue that also serves as the home of the London Symphony Orchestra, have rec...
03/07/2026
Caden Pearson appointed new Commissioning Editor for NITV
3 July, 2026
Media releases
National Indigenous Television (NITV) has strengthened its commitment...
03/07/2026
1 February 2023
SHARE Facebook Twitter Linkedin Email
Munich, Germany, 1st February 2023: Cinegy GmbH, the premier provider of software technology for digit...
03/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
03/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
03/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
03/07/2026
Death Star
Andy Marken July 2, 2026
0 Comments
Look, I can't get involved. I've got work to do. It's not that I like the Empire; I hate i...
03/07/2026
Berklee's New Visual Identity: Honoring Our History, Building for What's...
03/07/2026
Scripps Research scientists awarded $2M to advance global disease surveillance Two Gates Foundation grants will expand wastewater surveillance and AI-driven dis...
03/07/2026
Joan Pulupa joins Scripps Research faculty to study the organization of DNA in brain cells and its links to neurodegeneration Using smell-sensing neurons and ad...
02/07/2026
Entering her senior year, this hometown girl is paving a career in live sports production gaining experience in replay and audio and as a TD
In the live-sports...
02/07/2026
In-venue and creative video staffers at the professional and collegiate level ha...
02/07/2026
BLAST, a competitive entertainment company focused on esports, has announced more than $133 million in revenue for 2025, representing more than 40% year-over-ye...
02/07/2026
Riedel Communications has announced official SKAARHOJ panel support for SimplyLive production workflows, enabled through the SimplyLive 2.1 release. The integra...
02/07/2026
The Fire Rescue Service of the Czech Republic has deployed LiveU video-over-bond...
02/07/2026
Gravity Media USA has announced the appointment of Brittney Boston as Head of Business Development, effective July 1, 2026. Based in Nashville, Tennessee, Bosto...
02/07/2026
TwelveLabs, a video intelligence company, has announced $100 million in Series B funding co-led by NEA and NAVER Ventures, with participation from Amazon, Radic...
02/07/2026
The Pro Padel League (PPL) has announced a broadcast partnership with USA Sports that will air five PPL championship matches on CNBC during the 2026 season, the...
02/07/2026
LiveLike, a digital fan engagement platform, has announced eight confirmed FIFA ...
02/07/2026
Cobalt Digital has received Future's Best of Show Award, presented by AV Technology at InfoComm 2026, for its blueCORE family of standalone signal processor...
02/07/2026
Synamedia has announced the appointment of Dr. Tzvi Gerstl as Chief Executive Officer. Paul Segre, who has served as CEO for the past six years, will transition...
02/07/2026
The Esports Foundation (EF) and Sony Group Corporation have announced an expanded collaboration for the Esports World Cup 2026 (EWC), taking place in Paris, Fra...
02/07/2026
Zee Entertainment Enterprises Ltd. ( Z') has announced exclusive broadcast and digital rights for the Bundesliga in India for five years, beginning with the...
02/07/2026
An effort uniting News, Sports, Local, and Telemundo, the 50+-camera live produc...
02/07/2026
Zoey Deutch, John Slattery, Ken Marino, Miles Gutierrez-Riley, and Ben Wang appe...
02/07/2026
Stammering, stuttering, strangulated tones
The Crow Hill Company's latest creation promises to be the most original sound set they've produced to d...
02/07/2026
A new era in unmixing and spectral editing
The latest version of Steinberg's spectral audio-editing software has just arrived, building on the strength...
02/07/2026
Aims to simplify additive synthesis
Sine Machine is the debut launch from Melatonin, a Vienna-based developer who have spent the past six years creating wha...
02/07/2026
Products to remain fully active & supported
Following the news of Native Instruments joining the inMusic brand line-up, Academy and Emmy Award-winning visua...
02/07/2026
What you missed!
Last weekend, Saturday 27 June 2026, saw the debut of Sound On Sounds new GearExpo UK event, the largest dedicated pro-audio event to take ...
02/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
02/07/2026
Following the successful launch of its inaugural APAC Mentoring Programme last month, the Rise AV APAC Regional Council will bring the conversation around mento...
02/07/2026
Blackmagic PYXIS 6K Used to Shoot Director Takahisa Zeze's Cry Out
Brie Clayton July 2, 2026
0 Comments
Highly mobile camera supports tense and de...
02/07/2026
Broadcast Solutions acquires BFE, expanding its lead in European broadcast, medi...
02/07/2026
Berklee Alum and Faculty Perform at Boston Public Library's 250th Anniversar...
02/07/2026
Broadcast Solutions GmbH, a leading systems integrator and provider of innovative solutions for the broadcast media industry, is acquiring BFE Studio und Medien...
02/07/2026
Cinegy GmbH, the premier provider of software-defined television technology, has extended the ingest facility at leading Brazilian sports company LiveMode, work...
02/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
02/07/2026
Standalone processors acknowledged for the innovation and value they bring to Pro AV
Cobalt Digital, a leading designer and manufacturer of signal processing ...
02/07/2026
Synamedia announced today the appointment of Dr Tzvi Gerstl as Chief Executive Officer. Paul Segre, who has served as CEO for the past six years, will transitio...
Scripps Research Institute Scientists Uncover a New Pathway that Regulates Information Processing in the Brain The Study Provides New Insight into Some Types of Mental Retardation
