How Our Brains Store Recent Memories, Cell by Single CellFindings may shed light on how to treat neurological conditions like Alzheimer’s and epilepsy
Confirming what neurocomputational theorists have long suspected, researchers at the Dignity Health Barrow Neurological Institute in Phoenix, Ariz. and University of California, San Diego School of Medicine report that the human brain locks down episodic memories in the hippocampus, committing each recollection to a distinct, distributed fraction of individual cells.
The findings, published in the June 16 Early Edition of PNAS, further illuminate the neural basis of human memory and may, ultimately, shed light on new treatments for diseases and conditions that adversely affect it, such as Alzheimer’s disease and epilepsy.
“To really understand how the brain represents memory, we must understand how memory is represented by the fundamental computational units of the brain – single neurons – and their networks,” said Peter N. Steinmetz, MD, PhD, program director of neuroengineering at Barrow and senior author of the study. “Knowing the mechanism of memory storage and retrieval is a critical step in understanding how to better treat the dementing illnesses affecting our growing elderly population.”
Steinmetz, with first author John T. Wixted, PhD, Distinguished Professor of Psychology, Larry R. Squire, PhD, professor in the departments of neurosciences, psychiatry and psychology, both at UC San Diego, and colleagues, assessed nine patients with epilepsy whose brains had been implanted with electrodes to monitor seizures. The monitoring recorded activity at the level of single neurons.
The patients memorized a list of words on a computer screen, then viewed a second, longer list that contained those words and others. They were asked to identify words they had seen earlier, and to indicate how well they remembered them. The observed difference in the cell-firing activity between words seen on the first list and those not on the list clearly indicated that cells in the hippocampus were representing the patients’ memories of the words.
The researchers found that recently viewed words were stored in a distributed fashion throughout the hippocampus, with a small fraction of cells, about 2 percent, responding to any one word and a small fraction of words, about 3 percent, producing a strong change in firing in these cells.
"Intuitively, one might expect to find that any neuron that responds to one item from the list would also respond to the other items from the list, but our results did not look anything like that. The amazing thing about these counterintuitive findings is that they could not be more in line with what influential neurocomputational theorists long ago predicted must be true," said Wixted.
Although only a small fraction of cells coded recent memory for any one word, the scientists said the absolute number of cells coding memory for each word was large nonetheless – on the order of hundreds of thousands at least. Thus, the loss of any one cell, they noted, would have a negligible impact on a person’s ability to remember specific words recently seen.
Ultimately, the scientists said their goal is to fully understand how the human brain forms and represents memories of places and things in everyday life, which cells are involved and how those cells are affected by illness and disease. The researchers will next attempt to determine whether similar coding is involved in memories of pictures of people and landmarks and how hippocampal cells representing memory are impacted in patients with more severe forms of epilepsy.
Pictured: Human neuron showing actin formation in response to stimulation. Michael A. Colicos, UC San Diego

How Our Brains Store Recent Memories, Cell by Single Cell
Findings may shed light on how to treat neurological conditions like Alzheimer’s and epilepsy

Confirming what neurocomputational theorists have long suspected, researchers at the Dignity Health Barrow Neurological Institute in Phoenix, Ariz. and University of California, San Diego School of Medicine report that the human brain locks down episodic memories in the hippocampus, committing each recollection to a distinct, distributed fraction of individual cells.

The findings, published in the June 16 Early Edition of PNAS, further illuminate the neural basis of human memory and may, ultimately, shed light on new treatments for diseases and conditions that adversely affect it, such as Alzheimer’s disease and epilepsy.

“To really understand how the brain represents memory, we must understand how memory is represented by the fundamental computational units of the brain – single neurons – and their networks,” said Peter N. Steinmetz, MD, PhD, program director of neuroengineering at Barrow and senior author of the study. “Knowing the mechanism of memory storage and retrieval is a critical step in understanding how to better treat the dementing illnesses affecting our growing elderly population.”

Steinmetz, with first author John T. Wixted, PhD, Distinguished Professor of Psychology, Larry R. Squire, PhD, professor in the departments of neurosciences, psychiatry and psychology, both at UC San Diego, and colleagues, assessed nine patients with epilepsy whose brains had been implanted with electrodes to monitor seizures. The monitoring recorded activity at the level of single neurons.

The patients memorized a list of words on a computer screen, then viewed a second, longer list that contained those words and others. They were asked to identify words they had seen earlier, and to indicate how well they remembered them. The observed difference in the cell-firing activity between words seen on the first list and those not on the list clearly indicated that cells in the hippocampus were representing the patients’ memories of the words.

The researchers found that recently viewed words were stored in a distributed fashion throughout the hippocampus, with a small fraction of cells, about 2 percent, responding to any one word and a small fraction of words, about 3 percent, producing a strong change in firing in these cells.

"Intuitively, one might expect to find that any neuron that responds to one item from the list would also respond to the other items from the list, but our results did not look anything like that. The amazing thing about these counterintuitive findings is that they could not be more in line with what influential neurocomputational theorists long ago predicted must be true," said Wixted.

Although only a small fraction of cells coded recent memory for any one word, the scientists said the absolute number of cells coding memory for each word was large nonetheless – on the order of hundreds of thousands at least. Thus, the loss of any one cell, they noted, would have a negligible impact on a person’s ability to remember specific words recently seen.

Ultimately, the scientists said their goal is to fully understand how the human brain forms and represents memories of places and things in everyday life, which cells are involved and how those cells are affected by illness and disease. The researchers will next attempt to determine whether similar coding is involved in memories of pictures of people and landmarks and how hippocampal cells representing memory are impacted in patients with more severe forms of epilepsy.

Pictured: Human neuron showing actin formation in response to stimulation. Michael A. Colicos, UC San Diego

How to Erase a Memory – And Restore It
Researchers at the University of California, San Diego School of Medicine have erased and reactivated memories in rats, profoundly altering the animals’ reaction to past events.
The study, published in the June 1 advanced online issue of the journal Nature, is the first to show the ability to selectively remove a memory and predictably reactivate it by stimulating nerves in the brain at frequencies that are known to weaken and strengthen the connections between nerve cells, called synapses.
“We can form a memory, erase that memory and we can reactivate it, at will, by applying a stimulus that selectively strengthens or weakens synaptic connections,” said Roberto Malinow, MD, PhD, professor of neurosciences and senior author of the study.
Scientists optically stimulated a group of nerves in a rat’s brain that had been genetically modified to make them sensitive to light, and simultaneously delivered an electrical shock to the animal’s foot. The rats soon learned to associate the optical nerve stimulation with pain and displayed fear behaviors when these nerves were stimulated.
Analyses showed chemical changes within the optically stimulated nerve synapses, indicative of synaptic strengthening.
In the next stage of the experiment, the research team demonstrated the ability to weaken this circuitry by stimulating the same nerves with a memory-erasing, low-frequency train of optical pulses. These rats subsequently no longer responded to the original nerve stimulation with fear, suggesting the pain-association memory had been erased.
In what may be the study’s most startlingly discovery, scientists found they could re-activate the lost memory by re-stimulating the same nerves with a memory-forming, high-frequency train of optical pulses. These re-conditioned rats once again responded to the original stimulation with fear, even though they had not had their feet re-shocked.
“We can cause an animal to have fear and then not have fear and then to have fear again by stimulating the nerves at frequencies that strengthen or weaken the synapses,” said Sadegh Nabavi, a postdoctoral researcher in the Malinow lab and the study’s lead author.
In terms of potential clinical applications, Malinow, who holds the Shiley Endowed Chair in Alzheimer’s Disease Research in Honor of Dr. Leon Thal, noted that the beta amyloid peptide that accumulates in the brains of people with Alzheimer’s disease weakens synaptic connections in much the same way that low-frequency stimulation erased memories in the rats. “Since our work shows we can reverse the processes that weaken synapses, we could potentially counteract some of the beta amyloid’s effects in Alzheimer’s patients,” he said.

How to Erase a Memory – And Restore It

Researchers at the University of California, San Diego School of Medicine have erased and reactivated memories in rats, profoundly altering the animals’ reaction to past events.

The study, published in the June 1 advanced online issue of the journal Nature, is the first to show the ability to selectively remove a memory and predictably reactivate it by stimulating nerves in the brain at frequencies that are known to weaken and strengthen the connections between nerve cells, called synapses.

“We can form a memory, erase that memory and we can reactivate it, at will, by applying a stimulus that selectively strengthens or weakens synaptic connections,” said Roberto Malinow, MD, PhD, professor of neurosciences and senior author of the study.

Scientists optically stimulated a group of nerves in a rat’s brain that had been genetically modified to make them sensitive to light, and simultaneously delivered an electrical shock to the animal’s foot. The rats soon learned to associate the optical nerve stimulation with pain and displayed fear behaviors when these nerves were stimulated.

Analyses showed chemical changes within the optically stimulated nerve synapses, indicative of synaptic strengthening.

In the next stage of the experiment, the research team demonstrated the ability to weaken this circuitry by stimulating the same nerves with a memory-erasing, low-frequency train of optical pulses. These rats subsequently no longer responded to the original nerve stimulation with fear, suggesting the pain-association memory had been erased.

In what may be the study’s most startlingly discovery, scientists found they could re-activate the lost memory by re-stimulating the same nerves with a memory-forming, high-frequency train of optical pulses. These re-conditioned rats once again responded to the original stimulation with fear, even though they had not had their feet re-shocked.

“We can cause an animal to have fear and then not have fear and then to have fear again by stimulating the nerves at frequencies that strengthen or weaken the synapses,” said Sadegh Nabavi, a postdoctoral researcher in the Malinow lab and the study’s lead author.

In terms of potential clinical applications, Malinow, who holds the Shiley Endowed Chair in Alzheimer’s Disease Research in Honor of Dr. Leon Thal, noted that the beta amyloid peptide that accumulates in the brains of people with Alzheimer’s disease weakens synaptic connections in much the same way that low-frequency stimulation erased memories in the rats. “Since our work shows we can reverse the processes that weaken synapses, we could potentially counteract some of the beta amyloid’s effects in Alzheimer’s patients,” he said.

Mutant Protein in Muscle Linked to Neuromuscular DisorderA new therapeutic target for Kennedy’s disease and a potential treatment 
Sometimes known as Kennedy’s disease, spinal and bulbar muscular atrophy (SBMA) is a rare inherited neuromuscular disorder characterized by slowly progressive muscle weakness and atrophy. Researchers have long considered it to be essentially an affliction of primary motor neurons – the cells in the spinal cord and brainstem that control muscle movement.
But in a new study published in the April 16, 2014 online issue of Neuron, a team of scientists at the University of California, San Diego School of Medicine say novel mouse studies indicate that mutant protein levels in muscle cells, not motor neurons, are fundamentally involved in SBMA, suggesting an alternative and promising new avenue of treatment for a condition that is currently incurable.
SBMA is an X-linked recessive disease that affects only males, though females carrying the defective gene have a 50:50 chance of passing it along to a son. It belongs to a group of diseases, such as Huntington’s disease, in which a C-A-G DNA sequence is repeated too many times, resulting in a protein with too many glutamines (an amino acid), causing the diseased protein to misfold and produce harmful consequences for affected cells. Thus far, human clinical trials of treatments to protect against these repeat toxicities have failed.
In the new paper, a team led by principal investigator Albert La Spada, MD, PhD, professor of pediatrics, cellular and molecular medicine, and neurosciences, and the associate director of the Institute for Genomic Medicine at UC San Diego, propose a different therapeutic target. After creating a new mouse model of SBMA, they discovered that skeletal muscle was the site of mutant protein toxicity and that measures which mitigated the protein’s influence in muscle suppressed symptoms of SBMA in treated mice, such as weight loss and progressive weakness, and increased survival.   
In a related paper, published in the April 16, 2014 online issue of Cell Reports, La Spada and colleagues describe a potential treatment for SBMA. Currently, there is none.
The scientists developed antisense oligonucleotides – sequences of synthesized genetic material – that suppressed androgen receptor (AR) gene expression in peripheral tissues, but not in the central nervous system. Mutations in the AR gene are the cause of SBMA, a discovery that La Spada made more than 20 years ago while a MD-PhD student.
La Spada said that antisense therapy helped mice modeling SBMA to recover lost muscle weight and strength and extended survival. 
“The main points of these papers is that we have identified both a genetic cure and a drug cure for SBMA – at least in mice. The goal now is to further develop and refine these ideas so that we can ultimately test them in people,” La Spada said.
Pictured: striated human skeletal muscle.

Mutant Protein in Muscle Linked to Neuromuscular Disorder
A new therapeutic target for Kennedy’s disease and a potential treatment

Sometimes known as Kennedy’s disease, spinal and bulbar muscular atrophy (SBMA) is a rare inherited neuromuscular disorder characterized by slowly progressive muscle weakness and atrophy. Researchers have long considered it to be essentially an affliction of primary motor neurons – the cells in the spinal cord and brainstem that control muscle movement.

But in a new study published in the April 16, 2014 online issue of Neuron, a team of scientists at the University of California, San Diego School of Medicine say novel mouse studies indicate that mutant protein levels in muscle cells, not motor neurons, are fundamentally involved in SBMA, suggesting an alternative and promising new avenue of treatment for a condition that is currently incurable.

SBMA is an X-linked recessive disease that affects only males, though females carrying the defective gene have a 50:50 chance of passing it along to a son. It belongs to a group of diseases, such as Huntington’s disease, in which a C-A-G DNA sequence is repeated too many times, resulting in a protein with too many glutamines (an amino acid), causing the diseased protein to misfold and produce harmful consequences for affected cells. Thus far, human clinical trials of treatments to protect against these repeat toxicities have failed.

In the new paper, a team led by principal investigator Albert La Spada, MD, PhD, professor of pediatrics, cellular and molecular medicine, and neurosciences, and the associate director of the Institute for Genomic Medicine at UC San Diego, propose a different therapeutic target. After creating a new mouse model of SBMA, they discovered that skeletal muscle was the site of mutant protein toxicity and that measures which mitigated the protein’s influence in muscle suppressed symptoms of SBMA in treated mice, such as weight loss and progressive weakness, and increased survival.   

In a related paper, published in the April 16, 2014 online issue of Cell Reports, La Spada and colleagues describe a potential treatment for SBMA. Currently, there is none.

The scientists developed antisense oligonucleotides – sequences of synthesized genetic material – that suppressed androgen receptor (AR) gene expression in peripheral tissues, but not in the central nervous system. Mutations in the AR gene are the cause of SBMA, a discovery that La Spada made more than 20 years ago while a MD-PhD student.

La Spada said that antisense therapy helped mice modeling SBMA to recover lost muscle weight and strength and extended survival. 

“The main points of these papers is that we have identified both a genetic cure and a drug cure for SBMA – at least in mice. The goal now is to further develop and refine these ideas so that we can ultimately test them in people,” La Spada said.

Pictured: striated human skeletal muscle.

Spheres of influence
Specific language impairment (SLI) is something of a misnomer. It’s a condition in which a person, typically first identified as a child, has difficulty speaking or communicating normally, but without obvious cause. Their hearing and general health are fine. There are no environmental or rearing experiences to explain it. There are no other signs of developmental delay or neurological disorder.
SLI seems hardly specific at all. And it’s the most common of childhood language disorders, affecting 7 percent of children.
“The primary requirements for the diagnosis are the failure to master spoken and written language expression and comprehension despite normal nonverbal intelligence and no sensory or other physical or medical condition that could cause it,” said Tim Brown, PhD, a developmental cognitive neuroscientist in the UC San Diego School of Medicine’s Department of Neurosciences and the UC San Diego Center for Human Development.
“Because it’s largely a diagnosis of exclusions, SLI likely has more than one cause and might be made up of different subtypes. Different kids with SLI can have very different profiles of language strengths and weaknesses.”
Although there are standard clinical treatments for speech production disorders, said Brown, there is no universally accepted treatment for SLI, in part because the problem is believed to involve non-motor “high-level” aspects of language.
In a recent paper published in the journal Frontiers in Human Neuroscience, Brown, Julia L. Evans, PhD, of the Center for Research in Language at UC San Diego and the School of Behavioral and Brain Sciences at the University of Texas, Dallas, and colleagues, describe using a technology called anatomically constrained magnetoencephalography imaging to look for “higher-level” aspects of language in a young SLI patient without requiring him to make speech movements or process auditory input.
They discovered that the adolescent boy’s brain represented objects in the opposite side of the brain than most people. “When he thinks about common objects, like a mouse, house, door, leaf or whale, and processes them vividly (like imagining their size), he uses his right brain hemisphere whereas most people rely most strongly on their left, which is thought to be the language processing hemisphere,” said Brown.
“This was true whether he was reading printed words of the objects or viewing pictures of them. With aMEG, we were able to show the specific regions of his brain that were used, with timing accurate down to the millisecond, which has not been seen before in SLI.”
Brown said the combination of spatial and temporal resolution gained using aMEG make it a promising method for better understanding what’s happening inside the brains of individual SLI patients. He said such precision may improve diagnoses and treatment.
“For example, although all children with SLI have language impairment, it may turn out that only a subset with SLI relies heavily on their right hemisphere for the cognitive processing of objects. Because of this difference in their brain’s functional organization, we might expect different cognitive or behavioral therapies to be effective for right hemisphere object processors versus left hemisphere processors. So the information about the individual child may be useful for both a better understanding of their problem and for leading them to a more appropriate treatment.”

Spheres of influence

Specific language impairment (SLI) is something of a misnomer. It’s a condition in which a person, typically first identified as a child, has difficulty speaking or communicating normally, but without obvious cause. Their hearing and general health are fine. There are no environmental or rearing experiences to explain it. There are no other signs of developmental delay or neurological disorder.

SLI seems hardly specific at all. And it’s the most common of childhood language disorders, affecting 7 percent of children.

“The primary requirements for the diagnosis are the failure to master spoken and written language expression and comprehension despite normal nonverbal intelligence and no sensory or other physical or medical condition that could cause it,” said Tim Brown, PhD, a developmental cognitive neuroscientist in the UC San Diego School of Medicine’s Department of Neurosciences and the UC San Diego Center for Human Development.

“Because it’s largely a diagnosis of exclusions, SLI likely has more than one cause and might be made up of different subtypes. Different kids with SLI can have very different profiles of language strengths and weaknesses.”

Although there are standard clinical treatments for speech production disorders, said Brown, there is no universally accepted treatment for SLI, in part because the problem is believed to involve non-motor “high-level” aspects of language.

In a recent paper published in the journal Frontiers in Human Neuroscience, Brown, Julia L. Evans, PhD, of the Center for Research in Language at UC San Diego and the School of Behavioral and Brain Sciences at the University of Texas, Dallas, and colleagues, describe using a technology called anatomically constrained magnetoencephalography imaging to look for “higher-level” aspects of language in a young SLI patient without requiring him to make speech movements or process auditory input.

They discovered that the adolescent boy’s brain represented objects in the opposite side of the brain than most people. “When he thinks about common objects, like a mouse, house, door, leaf or whale, and processes them vividly (like imagining their size), he uses his right brain hemisphere whereas most people rely most strongly on their left, which is thought to be the language processing hemisphere,” said Brown.

“This was true whether he was reading printed words of the objects or viewing pictures of them. With aMEG, we were able to show the specific regions of his brain that were used, with timing accurate down to the millisecond, which has not been seen before in SLI.”

Brown said the combination of spatial and temporal resolution gained using aMEG make it a promising method for better understanding what’s happening inside the brains of individual SLI patients. He said such precision may improve diagnoses and treatment.

“For example, although all children with SLI have language impairment, it may turn out that only a subset with SLI relies heavily on their right hemisphere for the cognitive processing of objects. Because of this difference in their brain’s functional organization, we might expect different cognitive or behavioral therapies to be effective for right hemisphere object processors versus left hemisphere processors. So the information about the individual child may be useful for both a better understanding of their problem and for leading them to a more appropriate treatment.”

Human neural progenitor cells isolated under selective culture conditions from the developing human brain and directed through lineage differentiation. Neural progenitor cells are stained green; differentiated astrocytes are orange. Nuclei are stained blue. Image courtesy of the National Institute of Neurological Disorders and Stroke. 
Protein Switch Dictates Cellular Fate: Stem Cell or Neuron
Researchers at the University of California, San Diego School of Medicine have discovered that a well-known protein has a new function: It acts in a biological circuit to determine whether an immature neural cell remains in a stem-like state or proceeds to become a functional neuron.
The findings, published in the February 13 online issue of Cell Reports, more fully illuminate a fundamental but still poorly understood cellular act – and may have significant implications for future development of new therapies for specific neurological disorders, including autism and schizophrenia.
Postdoctoral fellow Chih-Hong Lou, working with principal investigator Miles F. Wilkinson, PhD, professor in the Department of Reproductive Medicine and a member of the UC San Diego Institute for Genomic Medicine, and other colleagues, discovered that this critical biological decision is controlled by UPF1, a protein essential for the nonsense-mediated RNA decay (NMD) pathway.
NMD was previously established to have two broad roles. First, it is a quality control mechanism used by cells to eliminate faulty messenger RNA (mRNA) – molecules that help transcribe genetic information into the construction of proteins essential to life.  Second, it degrades a specific group of normal mRNAs.  The latter function of NMD has been hypothesized to be physiologically important, but until now it had not been clear whether this is the case.
Wilkinson and colleagues discovered that in concert with a special class of RNAs called microRNA, UPF1 acts as a molecular switch to determine when immature (non-functional) neural cells differentiate into non-dividing (functional) neurons. Specifically, UPF1 triggers the decay of a particular mRNA that encodes for a protein in the TGF-? signaling pathway that promotes neural differentiation.  By degrading that mRNA, the encoded protein fails to be produced and neural differentiation is prevented.  Thus, Lou and colleagues identified for the first time a molecular circuit in which NMD acts to drive a normal biological response.
NMD also promotes the decay of mRNAs encoding proliferation inhibitors, which Wilkinson said may explain why NMD stimulates the proliferative state characteristic of stem cells. 
“There are many potential clinical ramifications for these findings,” Wilkinson said. “One is that by promoting the stem-like state, NMD may be useful for reprogramming differentiated cells into stem cells more efficiently. 
“Another implication follows from the finding that NMD is vital to the normal development of the brain in diverse species, including humans.  Humans with deficiencies in NMD have intellectual disability and often also have schizophrenia and autism. Therapies to enhance NMD in affected individuals could be useful in restoring the correct balance of stem cells and differentiated neurons and thereby help restore normal brain function.”

Human neural progenitor cells isolated under selective culture conditions from the developing human brain and directed through lineage differentiation. Neural progenitor cells are stained green; differentiated astrocytes are orange. Nuclei are stained blue. Image courtesy of the National Institute of Neurological Disorders and Stroke.

Protein Switch Dictates Cellular Fate: Stem Cell or Neuron

Researchers at the University of California, San Diego School of Medicine have discovered that a well-known protein has a new function: It acts in a biological circuit to determine whether an immature neural cell remains in a stem-like state or proceeds to become a functional neuron.

The findings, published in the February 13 online issue of Cell Reports, more fully illuminate a fundamental but still poorly understood cellular act – and may have significant implications for future development of new therapies for specific neurological disorders, including autism and schizophrenia.

Postdoctoral fellow Chih-Hong Lou, working with principal investigator Miles F. Wilkinson, PhD, professor in the Department of Reproductive Medicine and a member of the UC San Diego Institute for Genomic Medicine, and other colleagues, discovered that this critical biological decision is controlled by UPF1, a protein essential for the nonsense-mediated RNA decay (NMD) pathway.

NMD was previously established to have two broad roles. First, it is a quality control mechanism used by cells to eliminate faulty messenger RNA (mRNA) – molecules that help transcribe genetic information into the construction of proteins essential to life.  Second, it degrades a specific group of normal mRNAs.  The latter function of NMD has been hypothesized to be physiologically important, but until now it had not been clear whether this is the case.

Wilkinson and colleagues discovered that in concert with a special class of RNAs called microRNA, UPF1 acts as a molecular switch to determine when immature (non-functional) neural cells differentiate into non-dividing (functional) neurons. Specifically, UPF1 triggers the decay of a particular mRNA that encodes for a protein in the TGF-? signaling pathway that promotes neural differentiation.  By degrading that mRNA, the encoded protein fails to be produced and neural differentiation is prevented.  Thus, Lou and colleagues identified for the first time a molecular circuit in which NMD acts to drive a normal biological response.

NMD also promotes the decay of mRNAs encoding proliferation inhibitors, which Wilkinson said may explain why NMD stimulates the proliferative state characteristic of stem cells. 

“There are many potential clinical ramifications for these findings,” Wilkinson said. “One is that by promoting the stem-like state, NMD may be useful for reprogramming differentiated cells into stem cells more efficiently. 

“Another implication follows from the finding that NMD is vital to the normal development of the brain in diverse species, including humans.  Humans with deficiencies in NMD have intellectual disability and often also have schizophrenia and autism. Therapies to enhance NMD in affected individuals could be useful in restoring the correct balance of stem cells and differentiated neurons and thereby help restore normal brain function.”

Daft about data

Apparently taking a break from their lab duties, a group of UC San Diego neuroscience students have put together a video paean to their tireless (but tiring) pursuit of data – usually while the rest of us are asleep.

The video, intended as a sort of invite to a Monday night social during next week’s Society for Neuroscience conference in San Diego, went viral, even appearing on Scientific American’s website. The UC San Diego video is inspired by Daft Punk’s song, “Get Lucky.” 

Judging from YouTube hits (more than 10,000 in just over a day for a video about doing things like gel electrophoresis), the neuroscience students got more than lucky. They’ve got a hit.

$100 Million Gift Launches Sanford Stem Cell Clinical CenterUC San Diego-based effort will speed discoveries to new drugs and treatments for patients
In a bold and singular step toward delivering the therapeutic promise of human stem cells, businessman and philanthropist T. Denny Sanford has committed $100 million to the creation of the Sanford Stem Cell Clinical Center at the University of California, San Diego.
The Sanford Center will accelerate development of drugs and cell therapies inspired by and derived from current human stem cell research; establishing, promoting and disseminating clinical trials and patient therapies that will help more quickly transform promise into reality.
“This gift and the creation of the Sanford Stem Cell Clinical Center will further UC San Diego’s leadership in stem cell science and therapeutics, and advance our region’s reputation as an international, collaborative hub for stem cell research,” said Pradeep K. Khosla, chancellor of UC San Diego. “This Center will support the goals and vision of our strategic planning process by translating discoveries into therapies that will improve and save lives.”
The Sanford Center will integrate operations at four locations: the UC San Diego Jacobs Medical Center and a nearby proposed clinical space, both scheduled to open in 2016; the UC San Diego Center for Advanced Laboratory Medicine (CALM); and the Sanford Consortium for Regenerative Medicine (SCRM). It will provide essential physical and human resources needed to leverage stem cell research currently being conducted at the Sanford Consortium – an innovative “collaboratory” of San Diego scientists from UC San Diego, the Sanford-Burnham Medical Research Institute, the Salk Institute for Biological Studies, The Scripps Research Institute and the La Jolla Institute for Allergy & Immunology – and other institutions on and around the Torrey Pines mesa, such as the J. Craig Venter Institute.
“Every day, scientists learn more about the regenerative powers of stem cells, which tantalize with their potential to treat, cure, even prevent, myriad afflictions, including cancer, Lou Gehrig’s disease and spinal cord injury. I see it in the amazing collaborative advances by researchers and doctors in the Consortium and across the La Jolla mesa,” said Sanford. “I believe we’re on the cusp of turning years of hard-earned knowledge into actual treatments for real people in need. I want this gift to push that reality faster and farther.”
More here

$100 Million Gift Launches Sanford Stem Cell Clinical Center
UC San Diego-based effort will speed discoveries to new drugs and treatments for patients

In a bold and singular step toward delivering the therapeutic promise of human stem cells, businessman and philanthropist T. Denny Sanford has committed $100 million to the creation of the Sanford Stem Cell Clinical Center at the University of California, San Diego.

The Sanford Center will accelerate development of drugs and cell therapies inspired by and derived from current human stem cell research; establishing, promoting and disseminating clinical trials and patient therapies that will help more quickly transform promise into reality.

“This gift and the creation of the Sanford Stem Cell Clinical Center will further UC San Diego’s leadership in stem cell science and therapeutics, and advance our region’s reputation as an international, collaborative hub for stem cell research,” said Pradeep K. Khosla, chancellor of UC San Diego. “This Center will support the goals and vision of our strategic planning process by translating discoveries into therapies that will improve and save lives.”

The Sanford Center will integrate operations at four locations: the UC San Diego Jacobs Medical Center and a nearby proposed clinical space, both scheduled to open in 2016; the UC San Diego Center for Advanced Laboratory Medicine (CALM); and the Sanford Consortium for Regenerative Medicine (SCRM). It will provide essential physical and human resources needed to leverage stem cell research currently being conducted at the Sanford Consortium – an innovative “collaboratory” of San Diego scientists from UC San Diego, the Sanford-Burnham Medical Research Institute, the Salk Institute for Biological Studies, The Scripps Research Institute and the La Jolla Institute for Allergy & Immunology – and other institutions on and around the Torrey Pines mesa, such as the J. Craig Venter Institute.

“Every day, scientists learn more about the regenerative powers of stem cells, which tantalize with their potential to treat, cure, even prevent, myriad afflictions, including cancer, Lou Gehrig’s disease and spinal cord injury. I see it in the amazing collaborative advances by researchers and doctors in the Consortium and across the La Jolla mesa,” said Sanford. “I believe we’re on the cusp of turning years of hard-earned knowledge into actual treatments for real people in need. I want this gift to push that reality faster and farther.”

More here

The image above depicts 12 functional regions of the brain clustered by genetic influence, either in terms of cortical thickness or by cortical surface area. The numbers identify specific regions. For cortical thickness: 1. Motor-premotor-supplementary area; 2. Superior parietal cortex; 3. Inferior parietal cortex; 4. Perisylvian region; 5. Occipital cortex; 6. Ventromedial occipital cortex; 7. Ventral frontal cortex; 8. Temporal pole; 9. Medial temporal cortex; 10. Middle temporal cortex; 11. Dorsolateral prefrontal cortex and 12. Medial prefrontal cortex. For surface area: 1. Motor-premotor cortex; 2. Dorsolateral prefrontal cortex; 3. Dorsomedial frontal cortex; 4. Orbitofrontal cortex; 5. Pars opercularis and subcentral region; 6. Superior temporal cortex; 7. Posterolateral temporal cortex; 8. Anteromedial temporal cortex; 9. Inferior parietal cortex; 10. Superior parietal cortex; 11. Precuneus; and 12. Occipital cortex.
Delving deeper into brain-building
Given its incredible structural complexity – 100 billion chattering neurons connected by a network of perhaps a quadrillion synaptic connections – it can hardly be surprising that the actual construction of a human brain is equally complex and marvelous.
A new paper by researchers at UC San Diego School of Medicine and VA San Diego Healthcare System underscores that point by plotting for the first time how genes influence the development and thickness of the cerebral cortex – the thin, outermost sheet of neural tissue, often dubbed “gray matter,” that plays a key role in high-level mental functions like memory, attention, perceptual awareness, thought, language and consciousness.
Writing in this week’s early edition of PNAS, William S. Kremen, PhD, professor of psychiatry, and colleagues describe mapping genetic influences and the varying thicknesses of the cortex.
The work adds a new dimension to a 2012 study by the same scientists that rendered the first atlas of the surface of the human brain based on genetic information.
“There are two major dimensions on the cortical ribbon or cortical sheet,” said first author Chi-Hua Chen, PhD. “One is the horizontal dimension for the expansion of surface area and the other is the vertical dimension for the size of cortical thickness. The 2012 work was to study the genetic topography of surface area; this study was to study cortical thickness.”
The researchers found that genetic influences work differently depending upon the direction taken during brain development. On the surface of the cortex, the effects are most striking horizontally, with maximum differences between those at the anterior or front of the brain compared to the posterior or back of the brain. With cortical thickness, the differences were dictated vertically, with maximum deviation measured dorsal (top) to ventral (bottom).
According to Chen, the findings confirm other evidence that cortical construction involves different mechanisms of brain development. “I think the importance and relevance of this study is that human cortical morphology is under genetic control that shows orderly spatial patterns on the cortical ribbon,” she said. Previous animal studies had suggested as much, but the concept of brain development through genetic gradation has not been well-studied in humans.
While there are no immediate clinical applications for the research, Chen and Kremen say the findings will further understanding of how complex genetic influences affect cortical morphology and aid future efforts to identify involved genes and associated neurological disorders.
“The genetic underpinnings of the brain are poorly understood, especially for the human brain,” said Kremen. “New genomic technologies are making it possible to explore this area and answer, from a genetic perspective, how genes affect brain development and how they are involved in neurological disorders like Alzheimer’s disease, mild cognitive impairment, schizophrenia and autism.

The image above depicts 12 functional regions of the brain clustered by genetic influence, either in terms of cortical thickness or by cortical surface area. The numbers identify specific regions. For cortical thickness: 1. Motor-premotor-supplementary area; 2. Superior parietal cortex; 3. Inferior parietal cortex; 4. Perisylvian region; 5. Occipital cortex; 6. Ventromedial occipital cortex; 7. Ventral frontal cortex; 8. Temporal pole; 9. Medial temporal cortex; 10. Middle temporal cortex; 11. Dorsolateral prefrontal cortex and 12. Medial prefrontal cortex. For surface area: 1. Motor-premotor cortex; 2. Dorsolateral prefrontal cortex; 3. Dorsomedial frontal cortex; 4. Orbitofrontal cortex; 5. Pars opercularis and subcentral region; 6. Superior temporal cortex; 7. Posterolateral temporal cortex; 8. Anteromedial temporal cortex; 9. Inferior parietal cortex; 10. Superior parietal cortex; 11. Precuneus; and 12. Occipital cortex.

Delving deeper into brain-building

Given its incredible structural complexity – 100 billion chattering neurons connected by a network of perhaps a quadrillion synaptic connections – it can hardly be surprising that the actual construction of a human brain is equally complex and marvelous.

A new paper by researchers at UC San Diego School of Medicine and VA San Diego Healthcare System underscores that point by plotting for the first time how genes influence the development and thickness of the cerebral cortex – the thin, outermost sheet of neural tissue, often dubbed “gray matter,” that plays a key role in high-level mental functions like memory, attention, perceptual awareness, thought, language and consciousness.

Writing in this week’s early edition of PNAS, William S. Kremen, PhD, professor of psychiatry, and colleagues describe mapping genetic influences and the varying thicknesses of the cortex.

The work adds a new dimension to a 2012 study by the same scientists that rendered the first atlas of the surface of the human brain based on genetic information.

“There are two major dimensions on the cortical ribbon or cortical sheet,” said first author Chi-Hua Chen, PhD. “One is the horizontal dimension for the expansion of surface area and the other is the vertical dimension for the size of cortical thickness. The 2012 work was to study the genetic topography of surface area; this study was to study cortical thickness.”

The researchers found that genetic influences work differently depending upon the direction taken during brain development. On the surface of the cortex, the effects are most striking horizontally, with maximum differences between those at the anterior or front of the brain compared to the posterior or back of the brain. With cortical thickness, the differences were dictated vertically, with maximum deviation measured dorsal (top) to ventral (bottom).

According to Chen, the findings confirm other evidence that cortical construction involves different mechanisms of brain development. “I think the importance and relevance of this study is that human cortical morphology is under genetic control that shows orderly spatial patterns on the cortical ribbon,” she said. Previous animal studies had suggested as much, but the concept of brain development through genetic gradation has not been well-studied in humans.

While there are no immediate clinical applications for the research, Chen and Kremen say the findings will further understanding of how complex genetic influences affect cortical morphology and aid future efforts to identify involved genes and associated neurological disorders.

“The genetic underpinnings of the brain are poorly understood, especially for the human brain,” said Kremen. “New genomic technologies are making it possible to explore this area and answer, from a genetic perspective, how genes affect brain development and how they are involved in neurological disorders like Alzheimer’s disease, mild cognitive impairment, schizophrenia and autism.

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