Research

Fred H. Gage, a professor in the Laboratory of Genetics, concentrates on the adult central nervous system and unexpected plasticity and adaptability to environmental stimulation that remains throughout the life of all mammals. His work may lead to methods of replacing or enhancing brain and spinal cord tissues lost or damaged due to Neurodegenerative disease or trauma.

Gage's lab showed that, contrary to accepted dogma, human beings are capable of growing new nerve cells throughout life. Small populations of immature nerve cells are found in the adult mammalian brain, a process called Neurogenesis. Gage is working to understand how these cells can be induced to become mature functioning nerve cells in the adult brain and spinal cord. They showed that environmental enrichment and physical exercise can enhance the growth of new brain cells and they are studying the underlying cellular and molecular mechanisms, that may be harnessed to repair the aged and damaged brain and spinal cord.

"How the adult central nervous system adapts to environmental stimulation may hold the key to new therapies that replace or enhance damaged brain and spinal cord tissues. That's why our lab is so intent on pursuing the mechanisms behind this process."

Like a frenzied file clerk, the hippocampus, a small seahorseshaped area located deep within the brain, processes and distributes memory to appropriate storage sections after readying the information for efficient recall. As it happens, the first relay station in the hippocampus, a part called the dentate gyrus, is also the brain's hotbed of neurogenesis. Neurogenesis, the process by which new neurons are added to the brain, declines with aging and is thought to be associated with some of the cognitive changes that take place as we grow older. What precise purpose these newborn neurons serve has been the topic of much debate, but apart from studies showing that they somehow contribute to hippocampus-dependent learning and memory, their exact function has remained unclear. A study in Gage's lab, however, has shed new light on their function.

While passing through the dentate gyrus, incoming signals are split up and distributed among ten times as many cells. This process, called pattern separation, is thought to help the brain separate individual events that are part of incoming memories.

Since the dentate gyrus also is where neurogenesis principally occurs, Gage and his team hypothesized that adding new neurons could help with the pattern separation. In experiments that specifically challenged this function of the dentate gyrus, researchers used different behavioral tasks and two distinct strategies to selectively shut down neurogenesis in this structure in mice. Those without neurogenesis had no problem recalling spatial information in general but were unable to discriminate between locations that were close to each other. This observation led Gage and his group to theorize that new brain cells help us to distinguish between memories that are closely related in space.

Contributing to pattern separation might not be the only function of new neurons in the adult brain, however; a computer model simulating the neuronal circuits in the dentate gyrus suggests an additional function: "time-stamping" memories by forming a link between individual elements of episodes occurring closely in time.

Left to right:
Front row: Carol Marie Marchetto, Sheryl Christenson, John Jepsen, Fred H. Gage, Lynne Moore, Yangling Mu, Jaso Ray, Diana Yu, Jessica Jou, Kim McIntyre, Chunmei Zhao

Second row: Iryna Gallina, Ben Hu, Xinwei Cao, Mohamedi Kagalwala, Ruth Keithley, James Aimone, Stephane Alfonso, Lara Rangel, Eunice Mejia, Andrea Pabon, Bobbi Miller, Bilal Kerman, Martin Regensburger, Dane Clemenson, Hoonkyo Suh, Chris Tse, Wei Deng and Yan Li

Last row: Tatjana Singer, Dien Sun, Dan Sepp, Arianna Mei, Paolo DiGiorgio, Ari Morcos, Ahmet Denli, Kristen Brennand, Beate Winner, Stefan Aigner, and Mike McConnell

Salk News Releases

• Salk scientist receives distinguished NIH award for transformative research
  September 28, 2011
• Salk Institute scientist garners international esteem on two continents
  June 20, 2011
• Patients' own cells yield new insights into the biology of schizophrenia
  April 13, 2011
• Stem Cell Leader Awarded $2.3 Million Grant for Parkinson's
  February 3, 2011
• Rett syndrome mobilizes jumping genes in the brain
  November 17, 2010
• Modeling autism in a dish
  November 11, 2010
• Work-life balance: Brain stem cells need their rest, too
  July 1, 2010
• American Philosophical Society inducts Fred H. Gage
  April 27, 2010
• Salk scientist has been elected a member of the European Molecular Biology Organization
  October 22, 2009
• Newborn brain cells show the way
  July 9, 2009
• Newborn brain cells "time-stamp" memories
  January 28, 2009
• A novel human stem cell-based model of ALS opens doors for rapid drug screening
  December 3, 2008
• Newborn neurons in the adult brain can settle in the wrong neighborhood
  November 10, 2008
• Salk Scientist Fred H. Gage to Receive the Keio Medical Science Prize
  October 15, 2008
• Salk researchers reprogram adult stem cells in their natural environment
  July 1, 2008
• UC San Diego and Salk Institute Establish Center to Study the Origin of Humans
  March 4, 2008
• Newborn brain cells modulate learning and memory
  January 30, 2008
• Newborn neurons like to hang with the in-crowd
  May 7, 2007
• Life and death in the hippocampus: what young neurons need to survive
  August 16, 2006
• Finding a cellular Neverland: How stem cells stay childlike
  June 27, 2006
• Human embryonic stem cells integrate successfully into mouse brain
  December 12, 2005
• "Jumping genes" contribute to the uniqueness of individual brains
  June 14, 2005
• Salk scientist Rusty Gage elected to American Academy of Arts and Sciences; Awardees also include sculptor, actor and Supreme Court Chief Justice
  May 4, 2005
• Current Human Embryonic Stem Cell Lines Contaminated With Potentially Dangerous Non-Human Molecule, UCSD/Salk Team Finds
  January 24, 2005
• New Findings Reopen Debate About Adult Stem Cell Plasticity
  July 21, 2004
• Stem Cell Regulator Could Hold Key to Staving Off Age-related Brain Changes
  January 30, 2004
• Gene Therapy Postpones Lou Gehrig's Disease Symptoms
  August 7, 2003
• Salk Professor Fred H. Gage Elected to National Academy of Sciences
  April 29, 2003
• Salk Scientists Demonstrate For The First Time That Newly Born Brain Cells Are Functional In The Adult Brain
  February 27, 2002
• Neural Progenitor Cells Recovered From Postmortem And Adult Tissue
  May 2, 2001
• Exercise Makes Mice Smarter, Salk Scientists Demonstrate
  November 8, 1999
• Running Boosts Number Of Brain Cells, According To New Salk Study
  February 22, 1999
• Human Brains Do Sprout New Cells According To New Salk Study
  November 1, 1998
• An Enriched Environment Stimulates An Increase In The Number Of Nerve Cells In Brains Of Older Mice
  April 24, 1997

Awards and Honors

• Fellow of the National Academy of Sciences
• Fellow of the Institute of Medicine of the National Academy of Sciences
• Fellow off the American Academy of Arts and Sciences
• Bristol-Myers Squibb Neuroscience Research Award, 1987
• IPSEN Prize in Neuronal Plasticity, 1990
• Charles A. Dana Award for Pioneering Achievements in Health and Education, 1993
• Christopher Reeve Research Medal, 1997
• Max Planck Research Prize, 1999
• The Robert J. and Claire Pasarow Foundation Award, 1999
• President, Society for Neuroscience, 2001
• Vi and John Adler Professor on Age-related Neurodegenerative Diseases, 2001
• MetLife Award for Medical Research, 2002
• Klaus Joachim Zulch-Preis through the Max Planck Society, 2003

Links

Gage lab

Gage technologies available for licensing

Patients' own cells yield new insights into the biology of schizophrenia

March 17, 2011

After a century of studying the causes of schizophrenia-the most persistent disabling condition among adults-the cause of the disorder remains unknown. Now induced pluripotent stem cells (iPSCs) generated from schizophrenic patients have brought researchers from the Salk Institute for Biological Studies a step closer to a fundamental understanding of the biological underpinnings of the disease. Read more>>