Monday, July 1, 2013

Welcome to Arisaka Lab's Blog

Why are we here? This is arguably the most fundamental question in human history, and that is the central theme of Arisaka Lab at UCLA.  We are trying to understand the origin of the Universe, life and consciousness altogether by yet-to-be-discovered physics laws.  Here we keep updating the latest news around the world related to our missions.
Please also visit Arisaka Lab's Homepage.

Friday, April 26, 2013

New Spin On Origins of Evolvability: Competition to Survive Not Necessary?

Scientists have long observed that species seem to have become increasingly capable of evolving in response to changes in the environment. But computer science researchers now say that the popular explanation of competition to survive in nature may not actually be necessary for evolvability to increase.   In a paper published this week inPLOS ONE, the researchers report that evolvability can increase over generations regardless of whether species are competing for food, habitat or other factors.  Using a simulated model they designed to mimic how organisms evolve, the researchers saw increasing evolvability even without competitive pressure.
Science Direct - Apr. 26, 2013

Joel Lehman, Kenneth O. Stanley.
Evolvability Is Inevitable: Increasing Evolvability without the Pressure to Adapt. 
PLoS ONE, 2013; 8 (4): e62186 DOI: 10.1371/journal.pone.0062186

Sunday, April 21, 2013

Stem Cell Transplant Restores Memory, Learning in Mice

 For the first time, human embryonic stem cells have been transformed into nerve cells that helped mice regain the ability to learn and remember.
A study at the University of Wisconsin-Madison is the first to show that human stem cells can successfully implant themselves in the brain and then heal neurological deficits, says senior author Su-Chun Zhang, a professor of neuroscience and neurology.  Once inside the mouse brain, the implanted stem cells formed two common, vital types of neurons, which communicate with the chemicals GABA or acetylcholine. "These two neuron types are involved in many kinds of human behavior, emotions, learning, memory, addiction and many other psychiatric issues," says Zhang.

Yan Liu, et al.
Medial ganglionic eminence–like cells derived from human embryonic stem cells correct learning and memory deficits. Nature Biotechnology, 2013; DOI:10.1038/nbt.2565

Monday, April 15, 2013

Brain Development Is Guided by Junk DNA That Isn't Really Junk

 Specific DNA once dismissed as junk plays an important role in brain development and might be involved in several devastating neurological diseases, UC San Francisco scientists have found.
Their discovery in mice is likely to further fuel a recent scramble by researchers to identify roles for long-neglected bits of DNA within the genomes of mice and humans alike. While researchers have been busy exploring the roles of proteins encoded by the genes identified in various genome projects, most DNA is not in genes. This so-called junk DNA has largely been pushed aside and neglected in the wake of genomic gene discoveries, the UCSF scientists said. In their own research, the UCSF team studies molecules called long noncoding RNA (lncRNA, often pronounced as "link" RNA), which are made from DNA templates in the same way as RNA from genes.
Science Daily, Apr. 15, 2013

Alexander D. Ramos, et al.
Integration of Genome-wide Approaches Identifies lncRNAs of Adult Neural Stem Cells and Their Progeny In Vivo.
Cell Stem Cell, 2013 DOI:10.1016/j.stem.2013.03.003

Friday, April 12, 2013

Deep Homology of Arthropod Central Complex and Vertebrate Basal Ganglia

Similarities of brain structure, function, and behavior are usually ascribed to convergent evolution. In their review, Strausfeld and Hirth (p. 157) identify multiple commonalities shared by vertebrate basal ganglia and a system of forebrain centers in arthropods called the central complex. The authors conclude that circuits essential to behavioral choice originated very early across phyla.

Nicholas J. Strausfeld, et al
Science 12 April 2013:
Vol. 340 no. 6129 pp. 157-161 , DOI: 10.1126/science.1231828

Thursday, April 11, 2013

See-through brains clarify connections

A chemical treatment that turns whole organs transparent offers a big boost to the field of ‘connectomics’ — the push to map the brain’s fiendishly complicated wiring. Scientists could use the technique to view large networks of neurons with unprecedented ease and accuracy. The technology also opens up new research avenues for old brains that were saved from patients and healthy donors.

Helen Shen
Nature 496, 151 (11 April 2013) doi:10.1038/496151a

Kwanghun Chung, et al
Structural and molecular interrogation of intact biological systems
Nature (2013) doi:10.1038/nature12107

Thursday, April 4, 2013

A 'Light Switch' in Brain Illuminates Neural Networks

 There are cells in your brain that recognize very specific places, and have that as one of their main jobs. These cells, called place cells, are found in an area behind your temple called the hippocampus. While these cells must be sent information from nearby cells to do their job, so far no one has been able to determine exactly what kind of nerve cells, or neurons, work with place cells to craft the code they create for each location. Neurons come in many different types with specialized functions. Some respond to edges and borders, others to specific locations, others act like a compass and react to which way you turn your head.
Science News Apr. 4, 2013 

Sheng-Jia Zhang*,†, Jing Ye*, Chenglin Miao, Albert Tsao, Ignas Cerniauskas, Debora Ledergerber, May-Britt Moser, Edvard I. Moser. Optogenetic Dissection of Entorhinal-Hippocampal Functional ConnectivityScience, 5 April 2013: Vol. 340 no. 6128 DOI: 10.1126/science.1232627

Thursday, March 28, 2013

Systematic Analysis of Neural Projections Reveals Clonal Composition of the Drosophila Brain

During development neurons are generated by sequential divisions of neural stem cells, or neuroblasts. In the insect brain progeny of certain stem cells form lineage-specific sets of projections that arborize in distinct brain regions, called clonal units. Though this raises the possibility that the entire neural network in the brain might be organized in a clone-dependent fashion, only a small portion of clones has been identified.

Our study showed that the insect brain is formed by a composition of cell-lineage-dependent modules. Clonal analysis reveals organized architecture even in those neuropils without obvious structural landmarks.

Current Biology, online 28 March 2013

Thursday, March 21, 2013

Forgetting in C. elegans Is Accelerated by Neuronal Communication via the TIR-1/JNK-1 Pathway

The control of memory retention is important for proper responses to constantly changing environments, but the regulatory mechanisms underlying forgetting have not been fully elucidated. Our genetic analyses in C. elegans revealed that mutants of the TIR-1/JNK-1 pathway exhibited prolonged retention of olfactory adaptation and salt chemotaxis learning. In olfactory adaptation, conditioning induces attenuation of odor-evoked Ca2+ responses in olfactory neurons, and this attenuation is prolonged in the TIR-1/JNK-1-pathway mutant animals. We also found that a pair of neurons in which the pathway functions is required for the acceleration of forgetting, but not for sensation or adaptation, in wild-type animals. In addition, the neurosecretion from these cells is important for the acceleration of forgetting. Therefore, we propose that these neurons accelerate forgetting through the TIR-1/JNK-1 pathway by sending signals that directly or indirectly stimulate forgetting.

Akitoshi Inoue, et al
Cell Reports, Volume 3, Issue 3, 808-819, 21 March 2013

Friday, March 15, 2013

Epigenetic mechanisms in the development and maintenance of dopaminergic neurons

Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral mesodiencephalon and are involved in psychiatric disorders and severely affected in neurodegenerative diseases such as Parkinson’s disease. mdDA neuronal development has received much attention in the last 15 years and many transcription factors involved in mdDA specification have been discovered. More recently however, the impact of epigenetic regulation has come into focus, and it’s emerging that the processes of histone modification and DNA methylation form the basis of genetic switches that operate during mdDA development. Here, we review the epigenetic control of mdDA development, maturation and maintenance. As we highlight, epigenetic mechanisms play a pivotal role in all of these processes and the knowledge gathered from studying epigenetics in these contexts may aid our understanding of mdDA-related pathologies.

Hendrikus J. van Heesbeen, et al
Development140, 1159-1169.   March 15, 2013

Saturday, January 26, 2013

Developmental processes in face perception

Understanding the developmental origins of face recognition has been the goal of many studies of various approaches. Contributions of experience-expectant mechanisms (early component), like perceptual narrowing, and lifetime experience (late component) to face processing remain elusive. By investigating captive chimpanzees of varying age, a rare case of a species with lifelong exposure to non-conspecific faces at distinctive levels of experience, we can disentangle developmental components in face recognition. We found an advantage in discriminating chimpanzee above human faces in young chimpanzees, reflecting a predominant contribution of an early component that drives the perceptual system towards the conspecific morphology, and an advantage for human above chimpanzee faces in old chimpanzees, reflecting a predominant late component that shapes the perceptual system along the critical dimensions of the face exposed to. We simulate the contribution of early and late components using computational modeling and mathematically describe the underlying functions.

Christoph D. Dahl, et al.
Published 09 January 2013

Friday, January 25, 2013

DNA and Quantum Dots: All That Glitters Is Not Gold

A team of researchers at the National Institute of Standards and Technology (NIST) has shown that by bringing gold nanoparticles close to the dots and using a DNA template to control the distances, the intensity of a quantum dot's fluorescence can be predictably increased or decreased. This breakthrough opens a potential path to using quantum dots as a component in better photodetectors, chemical sensors and nanoscale lasers.
Seung Hyeon Ko, Kan Du, J. Alexander Liddle.
Quantum-Dot Fluorescence Lifetime Engineering with DNA Origami Constructs. 
Angewandte Chemie International Edition, 2013; 52 (4): 1193 DOI:10.1002/anie.201206253

Thursday, January 24, 2013

Scientists Discover How Epigenetic Information Could Be Inherited: Mechanism of Epigenetic Reprogramming Revealed

New research reveals a potential way for how parents' experiences could be passed to their offspring's genes. The research was published January, 25 in the journal Science.
Science Daily, Jan 25, 2013

Mouse primordial germ cells (PGCs) undergo sequential epigenetic changes and genome-wide DNA demethylation to reset the epigenome for totipotency. Here, the authors demonstrate that erasure of CpG methylation (5mC) in PGCs occurs via conversion to 5-hydroxymethylcytosine (5hmC), driven by high levels of TET1 and TET2. Global conversion to 5hmC initiates asynchronously among PGCs at embryonic day (E) 9.5 to E10.5 and accounts for the unique process of imprint erasure. Mechanistically, 5hmC enrichment is followed by its protracted decline thereafter at a rate consistent with replication-coupled dilution. The conversion to 5hmC is an important component of parallel redundant systems that drive comprehensive reprogramming in PGCs. Nonetheless, they identify rare regulatory elements that escape systematic DNA demethylation in PGCs, providing a potential mechanistic basis for transgenerational epigenetic inheritance.

Jamie A. Hackett, et al.Science 25 January 2013:
Vol. 339 no. 6118 pp. 448-452
DOI: 10.1126/science.12292

Wednesday, January 23, 2013

Action Plan: Making Brain-Controlled Prosthetics That Can Open a Clothespin

Brain-controlled interfaces have advanced dramatically during the past decade. But more work needs to be done before this technology begins to approximate the natural movements of a fully functioning arm or hand. An attempt to replicate the full range of movement—and the cognitive chain of events from thought to action—has now begun as a research collaboration among the California Institute of Technology, Johns Hopkins University Applied Physics Laboratory, the University of Southern California and Rancho Los Amigos National Rehabilitation Center. These institutions are seeking a few recruits to be fitted with a $500,000 robotic limb.

By Gary Stix,  January 23, 2013, Scientific American

Billion-euro brain simulation and graphene projects win European funds

The European Commission has selected the two research proposals it will fund to the tune of half-a-billion euros each after a two-year, high-profile contest. The Human Brain Project, led by neuroscientist Henry Markram at the Swiss Federal Institute of Technology (EPFL) in Lausanne, plans to simulate everything known about the human brain in a supercomputer — a breathtaking ambition that has been met with some scepticism (See “Brain in a box”).

NATURE | BREAKING NEWS, 23 January 2013
Nature 482, 456–458 (23 February 2012) doi:10.1038/482456a

Synthetic double-helix faithfully stores Shakespeare's sonnets

A team of scientists has produced a truly concise anthology of verse by encoding all 154 of Shakespeare’s sonnets in DNA. The researchers say that their technique could easily be scaled up to store all of the data in the world. Along with the sonnets, the team encoded a 26-second audio clip from Martin Luther King’s famous “I have a dream" speech, a copy of James Watson and Francis Crick’s classic paper on the structure of DNA, a photo of the researchers' institute and a file that describes how the data were converted. The researchers report their results today on Nature’s website.
DNA packs information into much less space than other media. For example, CERN, the European particle-physics lab near Geneva, currently stores around 90 petabytes of data on some 100 tape drives. Goldman’s method could fit all of those data into 41 grams of DNA.
Nature News, 23 January 2013

Towards practical, high-capacity, low-maintenance information storage in synthesized DNAGoldman, N. et al. Nature (2013).

Sunday, January 20, 2013

Grid cells require excitatory drive from the hippocampus

To determine how hippocampal backprojections influence spatially periodic firing in grid cells, the author recorded neural activity in the medial entorhinal cortex (MEC) of rats after temporary inactivation of the hippocampus. They report two major changes in entorhinal grid cells. First, hippocampal inactivation gradually and selectively extinguished the grid pattern. Second, the same grid cells that lost their grid fields acquired substantial tuning to the direction of the rat's head. This transition in firing properties was contingent on a drop in the average firing rate of the grid cells and could be replicated by the removal of an external excitatory drive in an attractor network model in which grid structure emerges by velocity-dependent translation of activity across a network with inhibitory connections. These results point to excitatory drive from the hippocampus, and possibly other regions, as one prerequisite for the formation and translocation of grid patterns in the MEC.

Tora Bonnevie, et al.
Nature Neuroscience (2013) doi:10.1038/nn.3311, Published online 20 January 2013

One Form of Neuron Turned Into Another in Brain

 A new finding by Harvard stem cell biologists turns one of the basics of neurobiology on its head -- demonstrating that it is possible to turn one type of already differentiated neuron into another within the brain. The discovery by Paola Arlotta and Caroline Rouaux "tells you that maybe the brain is not as immutable as we always thought, because at least during an early window of time one can reprogram the identity of one neuronal class into another," said Arlotta.

Caroline Rouaux, Paola Arlotta.
Direct lineage reprogramming of post-mitotic callosal neurons into corticofugal neurons in vivo. 

Recurrent inhibitory circuitry as a mechanism for grid formation

Grid cells in layer II of the medial entorhinal cortex form a principal component of the mammalian neural representation of space. The firing pattern of a single grid cell has been hypothesized to be generated through attractor dynamics in a network with a specific local connectivity including both excitatory and inhibitory connections. However, experimental evidence supporting the presence of such connectivity among grid cells in layer II is limited. Here we report recordings from more than 600 neuron pairs in rat entorhinal slices, demonstrating that stellate cells, the principal cell type in the layer II grid network, are mainly interconnected via inhibitory interneurons. Using a model attractor network, we demonstrate that stable grid firing can emerge from a simple recurrent inhibitory network. Our findings thus suggest that the observed inhibitory microcircuitry between stellate cells is sufficient to generate grid-cell firing patterns in layer II of the medial entorhinal cortex.

Jonathan J Couey, et al.
Nature Neuroscience (2013) doi:10.1038/nn.3310, Published online 20 January 2013

Mars May Have Supported Life: Martian Underground Could Contain Clues to Life's Origins

Minerals found in the subsurface of Mars, a zone of more than three miles below ground, make for the strongest evidence yet that the red planet may have supported life, according to research "Groundwater activity on Mars and implications for a deep biosphere," published inNature Geoscience on January 20, 2013.
Science Daily, Jan 20, 2013

Joseph R. Michalski, et al.
Wright.Groundwater activity on Mars and implications for a deep biosphere.

Saturday, January 19, 2013

Nearby Universe's 'Cosmic Fog' Measured

HESS collaboration has carried out the first measurement of the intensity of the diffuse extragalactic background light in the nearby Universe, a fog of photons that has filled the Universe ever since its formation. Using some of the brightest gamma-ray sources in the southern hemisphere, the study was carried out using measurements performed by the HESS telescope array, located in Namibia and involving CNRS and CEA. The study is complementary to that recently carried out by the Fermi-LAT space observatory. These findings provide new insight into the size of the Universe observable in gamma rays and shed light on the formation of stars and the evolution of galaxies.
Science Daily, Jan 19, 2013

A. Abramowski et al.
Measurement of the extragalactic background light imprint on the spectra of the brightest blazars observed with H.E.S.S..
Astronomy & Astrophysics, 2013; 550: A4 DOI: 10.1051/0004-6361/201220355

Friday, January 18, 2013

The Cell That Isn't: New Technique Captures Division of Membrane-Less Cells

A new technique allows scientists to study cell division without a cell membrane. There are several advantages: it can be physically constrained and manipulated; one can access nuclei which is normally buried deep in an opaque embryo; the method ican be combined with a wide-range of fruit fly genetics techniques. The method has revealed that, surprisingly, confined space not enough to restrict spindle size.
Science Daily, Jan 18 2013

Ivo A Telley, Imre Gáspár, Anne Ephrussi, Thomas Surrey.
A single Drosophila embryo extract for the study of mitosis ex vivo. 
Nature Protocols, 2013; 8 (2): 310 DOI:10.1038/nprot.2013.003

The evolutionary causes and consequences of sex-biased gene expression

Females and males often differ extensively in their physical traits. This sexual dimorphism is largely caused by differences in gene expression. Recent advances in genomics, such as RNA sequencing (RNA-seq), have revealed the nature and extent of sex-biased gene expression in diverse species. Here the authors highlight new findings regarding the causes of sex-biased expression, including sexual antagonism and incomplete dosage compensation. they also discuss how sex-biased expression can accelerate the evolution of sex-linked genes.

RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond

A growing number of functions are emerging for RNA interference (RNAi) in the nucleus, in addition to well-characterized roles in post-transcriptional gene silencing in the cytoplasm. Epigenetic modifications directed by small RNAs have been shown to cause transcriptional repression in plants, fungi and animals. Additionally, increasing evidence indicates that RNAi regulates transcription through interaction with transcriptional machinery. Nuclear small RNAs include small interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs) and are implicated in nuclear processes such as transposon regulation, heterochromatin formation, developmental gene regulation and genome stability.

Stephane E. Castel
Nature Reviews Genetics 14, 100-112 (February 2013) |doi:10.1038/nrg3355

Y-chromosome evolution: emerging insights into processes of Y-chromosome degeneration

The human Y chromosome is intriguing not only because it harbours the master-switch gene that determines gender but also because of its unusual evolutionary history. The Y chromosome evolved from an autosome, and its evolution has been characterized by massive gene decay. Recent whole-genome and transcriptome analyses of Y chromosomes in humans and other primates, in Drosophila species and in plants have shed light on the current gene content of the Y chromosome, its origins and its long-term fate. Furthermore, comparative analysis of young and old Y chromosomes has given further insights into the evolutionary and molecular forces triggering Y-chromosome degeneration and into the evolutionary destiny of the Y chromosome.

Doris Bachtrog
Nature Reviews Genetics 14, 113-124 (February 2013) | doi:10.1038/nrg3366

Thursday, January 17, 2013

Human brain evolution: transcripts, metabolites and their regulators

What evolutionary events led to the emergence of human cognition? Although the genetic differences separating modern humans from both non-human primates (for example, chimpanzees) and archaic hominins (Neanderthals and Denisovans) are known, linking human-specific mutations to the cognitive phenotype remains a challenge.  The new strategy is to focus on human-specific changes at the level of intermediate phenotypes, such as gene expression and metabolism, in conjunction with evolutionary changes in gene regulation involving transcription factors, microRNA and proximal regulatory elements. In this Review the authors show how this strategy has yielded some of the first hints about the mechanisms of human cognition.

Discrete genetic modules are responsible for complex burrow evolution in Peromyscus mice

The genetics of behavioural differences between closely related species are less well understood than the genetics of morphological differences. Many animals build elaborate structures — such as hives, nests and burrows — that 'evolve' as natural selection acts on the behaviour of their builders. This study uses an example of this phenomenon to tackle the question of whether complex behaviours evolve through one or few genetic changes that each influence many aspects of behaviour, or by accumulation of several genetic changes that generate behavioural complexity only when combined. Hopi Hoekstra and colleagues show that the complex burrows created by oldfield mice are governed by several genetic modules, each controlling an aspect of burrow size or shape. This modularity in burrow architecture suggests that complex behaviour may result from the combination of genetically determined behaviours that have accumulated over time.

Jesse N. Weber, et al.

Why Wolves Are Forever Wild, but Dogs Can Be Tamed

Dogs and wolves are genetically so similar, it's been difficult for biologists to understand why wolves remain fiercely wild, while dogs can gladly become "man's best friend." Now, doctoral research by evolutionary biologist Kathryn Lord at the University of Massachusetts Amherst suggests the different behaviors are related to the animals' earliest sensory experiences and the critical period of socialization. Details appear in the current issue of Ethology.

When the socialization window is open, wolf and dog pups begin walking and exploring without fear and will retain familiarity throughout their lives with those things they contact. Domestic dogs can be introduced to humans, horses and even cats at this stage and be comfortable with them forever. But as the period progresses, fear increases and after the window closes, new sights, sounds and smells will elicit a fear response.  Through observations, Lord confirmed that both wolf pups and dogs develop the sense of smell at age two weeks, hearing at four weeks and vision by age six weeks on average. However, these two subspecies enter the critical period of socialization at different ages. Dogs begin the period at four weeks, while wolves begin at two weeks. Therefore, how each subspecies experiences the world during that all-important month is extremely different, and likely leads to different developmental paths, she says.
Science Daily, Jan. 17, 2013

Kathryn Lord.
A Comparison of the Sensory Development of Wolves (Canis lupus lupus) and Dogs (Canis lupus familiaris). 
Ethology, 2013; 119 (2): 110 DOI:10.1111/eth.12044

Wednesday, January 16, 2013

Light Switch Inside Brain: Laser Controls Individual Nerve Cells in Mouse

Activating and deactivating individual nerve cells in the brain is something many neuroscientists wish they could do, as it would help them to better understand how the brain works.  Scientists in Freiburg and Basel, Switzerland, have developed an implant that is able to genetically modify specific nerve cells, control them with light stimuli, and measure their electrical activity all at the same time. This novel 3-in-1 tool paves the way for completely new experiments in neurobiology.

A polymer-based neural microimplant for optogenetic applications: design and first in vivo study
Birthe Rubehn, et al.
Lab Chip, 2013, Advance Article
DOI: 10.1039/C2LC40874K, First published on the web 03 Jan 2013

Monday, January 14, 2013

Memory on time

Considerable recent work has shown that the hippocampus is critical for remembering the order of events in distinct experiences, a defining feature of episodic memory. Correspondingly, hippocampal neuronal activity can ‘replay’ sequential events in memories and hippocampal neuronal ensembles represent a gradually changing temporal context signal. Most strikingly, single hippocampal neurons – called time cells – encode moments in temporally structured experiences much as the well-known place cells encode locations in spatially structured experiences. These observations bridge largely disconnected literatures on the role of the hippocampus in episodic memory and spatial mapping, and suggest that the fundamental function of the hippocampus is to establish spatio-temporal frameworks for organizing memories.

Howard Eichenbaum
Trends in Cognitive Sciences, 14 January 2013

New Implant Replaces Impaired Middle Ear

Functionally deaf patients can gain normal hearing with a new implant that replaces the middle ear. The unique invention from the Chalmers University of Technology has been approved for a clinical study. The first operation was performed on a patient in December 2012.

Sunday, January 13, 2013

Lag normalization in an electrically coupled neural network

Moving objects can cover large distances while they are processed by the eye, usually resulting in a spatially lagged retinal response. The authors identified a network of electrically coupled motion–coding neurons in mouse retina that act collectively to register the leading edges of moving objects at a nearly constant spatial location, regardless of their velocity. These results reveal a previously unknown neurophysiological substrate for lag normalization in the visual system.

Stuart Trenholm, et al.
Nature Neuroscience (2013) doi:10.1038/nn.3308, Published online 13 January 2013

Layer-specific excitatory circuits differentially control recurrent network dynamics in the neocortex

In the absence of external stimuli, the mammalian neocortex shows intrinsic network oscillations. These dynamics are characterized by translaminar assemblies of neurons whose activity synchronizes rhythmically in space and time. How different cortical layers influence the formation of these spontaneous cellular assemblies is poorly understood. The author found that excitatory neurons in supragranular and infragranular layers have distinct roles in the regulation of intrinsic low-frequency oscillations in mice in vivo. Optogenetic activation of infragranular neurons generated network activity that resembled spontaneous events, whereas photoinhibition of these same neurons substantially attenuated slow ongoing dynamics. In contrast, light activation and inhibition of supragranular cells had modest effects on spontaneous slow activity. This study represents, to the best of our knowledge, the first causal demonstration that excitatory circuits located in distinct cortical layers differentially control spontaneous low-frequency dynamics.

Riccardo Beltramo,  et al.
Nature Neuroscience (2013) doi:10.1038/nn.3306, Published online 13 January 2013

Friday, January 11, 2013

Biggest Structure in Universe: Large Quasar Group Is 4 Billion Light Years Across

An international team of astronomers, led by academics from the University of Central Lancashire (UCLan), has found the largest known structure in the universe. The large quasar group (LQG) is so large that it would take a vehicle travelling at the speed of light some 4 billion years to cross it.

Roger G. Clowes, et al.
A structure in the early Universe at z ∼ 1.3 that exceeds the homogeneity scale of the R-W concordance cosmology. 
Monthly Notices of the Royal Astronomical Society, January 11, 2013 DOI:10.1093/mnras/sts497

Multiple Fitness Peaks on the Adaptive Landscape Drive Adaptive Radiation in the Wild

Increased competition is shown to drive multiple peaks in fitness during the adaptive radiation of a species.   The relationship between phenotype and fitness can be visualized as a rugged landscape. Multiple fitness peaks on this landscape are predicted to drive early bursts of niche diversification during adaptive radiation. The authors measured the adaptive landscape in a nascent adaptive radiation of Cyprinodonpupfishes endemic to San Salvador Island, Bahamas, and found multiple coexisting high-fitness regions driven by increased competition at high densities, supporting the early burst model. Hybrids resembling the generalist phenotype were isolated on a local fitness peak separated by a valley from a higher-fitness region corresponding to trophic specialization. This complex landscape could explain both the rarity of specialists across many similar environments due to stabilizing selection on generalists and the rapid morphological diversification rate of specialists due to their higher fitness.

Christopher H. Martin, Peter C. Wainwright
Science 11 January 2013: Vol. 339 no. 6116 pp. 208-211, DOI: 10.1126/science.1227710

Thursday, January 10, 2013

Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants

Understanding the extent, distribution and age of human protein-coding genetic variants across diverse populations allows fascinating insights into human population dynamics and the resultant evolutionary forces. Cataloguing and dating such variation will also allow us to understand the origin of the seemingly endless list of potential disease variants and to prioritize among them for further investigation. A recent study describes the sequencing of 15,336 genes in 4,298 individuals of European American and 2,217 individuals of African American ancestry, providing insights into a recent human population expansion and the associated evolution of disease variants.

Fu, W. et al

Regenerate Sensory Hair Cells, Restore Hearing to Noise-Damaged Ears

Hearing loss is a significant public health problem affecting almost 50 million people in the United States alone. Sensorineural hearing loss is the most common form and is caused by the loss of sensory hair cells in the cochlea. Hair cell loss results from a variety of factors including noise exposure, aging, toxins, infections, and certain antibiotics and anti-cancer drugs. Although hearing aids and cochlear implants can ameliorate the symptoms somewhat, there are no known treatments to restore hearing, because auditory hair cells in mammals, unlike those in birds or fish, do not regenerate once lost. Auditory hair cell replacement holds great promise as a treatment that could restore hearing after loss of hair cells.

In the Jan. 10 issue of Neuron, Massachusetts Eye and Ear and Harvard Medical School researchers demonstrate for the first time that hair cells can be regenerated in an adult mammalian ear by using a drug to stimulate resident cells to become new hair cells, resulting in partial recovery of hearing in mouse ears damaged by noise trauma. This finding holds great potential for future therapeutic application that may someday reverse deafness in humans.

Notch Inhibition Induces Cochlear Hair Cell Regeneration and Recovery of Hearing after Acoustic Trauma
Kunio Mizutari, et al.
Neuron, Volume 77, Issue 1, 58-69, 9 January 2013, 10.1016/j.neuron.2012.11.032

Wednesday, January 9, 2013

Microglia: New Roles for the Synaptic Stripper

Any pathologic event in the brain leads to the activation of microglia, the immunocompetent cells of the central nervous system. In recent decades diverse molecular pathways have been identified by which microglial activation is controlled and by which the activated microglia affects neurons. In the normal brain microglia were considered “resting,” but it has recently become evident that they constantly scan the brain environment and contact synapses. Activated microglia can remove damaged cells as well as dysfunctional synapses, a process termed “synaptic stripping.” Here the author summarize evidence that molecular pathways characterized in pathology are also utilized by microglia in the normal and developing brain to influence synaptic development and connectivity, and therefore should become targets of future research. Microglial dysfunction results in behavioral deficits, indicating that microglia are essential for proper brain function. This defines a new role for microglia beyond being a mere pathologic sensor.

Neuron, Volume 77, Issue 1, 10-18, 9 January 2013, 10.1016/j.neuron.2012.12.023

Feedback Inhibition Enables Theta-Nested Gamma Oscillations and Grid Firing Fields

Cortical circuits are thought to multiplex firing rate codes with temporal codes that rely on oscillatory network activity, but the circuit mechanisms that combine these coding schemes are unclear. The authors establish with optogenetic activation of layer II of the medial entorhinal cortex that theta frequency drive to this circuit is sufficient to generate nested gamma frequency oscillations in synaptic activity. These nested gamma oscillations closely resemble activity during spatial exploration, are generated by local feedback inhibition without recurrent excitation, and have clock-like features suitable as reference signals for multiplexing temporal codes within rate-coded grid firing fields. In network models deduced from our data, feedback inhibition supports coexistence of theta-nested gamma oscillations with attractor states that generate grid firing fields. These results indicate that grid cells communicate primarily via inhibitory interneurons. This circuit mechanism enables multiplexing of oscillation-based temporal codes with rate-coded attractor states.

Hugh Pastoll, et al.
Neuron, Volume 77, Issue 1, 141-154, 9 January 2013, 10.1016/j.neuron.2012.11.032

Shaping Our Minds: Stem and Progenitor Cell Diversity in the Mammalian Neocortex

The neural circuits of the mammalian neocortex are crucial for perception, complex thought, cognition, and consciousness. This circuitry is assembled from many different neuronal subtypes with divergent properties and functions. Here, we review recent studies that have begun to clarify the mechanisms of cell-type specification in the neocortex, focusing on the lineage relationships between neocortical progenitors and subclasses of excitatory projection neurons. These studies reveal an unanticipated diversity in the progenitor pool that requires a revised view of prevailing models of cell-type specification in the neocortex. We propose a “sequential progenitor-diversification model” that integrates current knowledge to explain how projection neuron diversity is achieved by mechanisms acting on proliferating progenitors and their postmitotic offspring. We discuss the implications of this model for our understanding of brain evolution and pathological states of the neocortex.

Neuron, Volume 77, Issue 1, 19-34, 9 January 2013, 10.1016/j.neuron.2012.12.022

Ion Channels | TRP Channels in Drosophila Auditory Transduction

In this study, Lehnert et al. record spikes and subthreshold activity from a genetically defined population ofDrosophila auditory receptor neurons. These recordings reveal that several TRP family members play distinct roles in converting movement to transduction currents.

Lehnert et al.
Neuron, Volume 77, Issue 1, 115-128, 9 January 2013

Eliminating Useless Information Important to Learning, Making New Memories

As we age, it just may be the ability to filter and eliminate old information -- rather than take in the new stuff -- that makes it harder to learn, scientists report.  "When you are young, your brain is able to strengthen certain connections and weaken certain connections to make new memories," said Dr. Joe Z. Tsien, neuroscientist at Georgia Regents University.  It's that critical weakening that appears hampered in the older brain, according to a study in the journalScientific Reports.

The NMDA receptor in the brain's hippocampus is like a switch for regulating learning and memory, working through subunits called NR2A and NR2B. NR2B is expressed in higher percentages in children, enabling neurons to talk a fraction of a second longer; make stronger bonds, called synapses; and optimize learning and memory. This formation of strong bonds is called long-term potentiation. The ratio shifts after puberty, so there is more NR2A and slightly reduced communication time between neurons.  When Tsien and his colleagues genetically modified mice that mimic the adult ratio -- more NR2A, less NR2B -- they were surprised to find the rodents were still good at making strong connections and short-term memories but had an impaired ability to weaken existing connections, called long-term depression, and to make new long-term memories as a result. It's called information sculpting and adult ratios of NMDA receptor subunits don't appear to be very good at it.

Science Daily, Jan 9, 2012 
Zhenzhong Cui, et al
Scientific Reports 3, Article number: 1036 doi:10.1038/srep01036

Monday, January 7, 2013

'Junk DNA' Made Visible Before the Final Cut

Research findings from the University of North Carolina School of Medicine are shining a light on an important regulatory role performed by the so-called dark matter, or "junk DNA," within each of our genes. The new study reveals snippets of information contained in dark matter that can alter the way a gene is assembled. "These small sequences of genetic information tell the gene how to splice, either by enhancing the splicing process or inhibiting it. The research opens the door for studying the dark matter of genes. And it helps us further understand how mutations or polymorphisms affect the functions of any gene," said study senior author, Zefeng Wang, PhD, assistant professor of pharmacology in the UNC School of Medicine and a member of UNC Lineberger Comprehensive Cancer Center.Science Daily - Jan. 7, 2013
Yang Wang, et al.
A complex network of factors with overlapping affinities represses splicing through intronic elements.
Nature Structural & Molecular Biology, 2012; 20 (1): 36 DOI: 10.1038/nsmb.2459