Timing to Perfection: The Biology of Central and Peripheral Circadian Clocks

The mammalian circadian system, which is comprised of multiple cellular clocks located in the organs and tissues, orchestrates their regulation in a hierarchical manner throughout the 24 hr of the day. At the top of the hierarchy are the suprachiasmatic nuclei, which synchronize subordinate organ and tissue clocks using electrical, endocrine, and metabolic signaling pathways that impact the molecular mechanisms of cellular clocks. The interplay between the central neural and peripheral tissue clocks is not fully understood and remains a major challenge in determining how neurological and metabolic homeostasis is achieved across the sleep-wake cycle. Disturbances in the communication between the plethora of body clocks can desynchronize the circadian system, which is believed to contribute to the development of diseases such as obesity and neuropsychiatric disorders. This review will highlight the relationship between clocks and metabolism, and describe how cues such as light, food, and reward mediate entrainment of the circadian system.

Urs Albrecht
Neuron Volume 74, Issue 2, 26 April 2012, Pages 246–260
http://www.sciencedirect.com/science/article/pii/S0896627312003327

Rats Match Humans in Decision-Making That Involves Combining Different Sensory Cues

The next time you set a trap for that rat running around in your basement, here's something to consider: you are going up against an opponent whose ability to assess the situation and make decisions is statistically just as good as yours.   A Cold Spring Harbor Laboratory (CSHL) study that compared the ability of humans and rodents to make perceptual decisions based on combining different modes of sensory stimuli -- visual and auditory cues, for instance -- has found that just like humans, rodents also combine multisensory information and exploit it in a "statistically optimal" way -- or the most efficient and unbiased way possible.
Science Daily, Mar. 13, 2012

David Raposo, et al.

Multisensory decision-making in rats and humans. Journal of Neuroscience, March 14, 2012 DOI:10.1523/JNEUROSCI.4998-11.2012

Rethinking the Emotional Brain

The author, LeDoux, proposes a reconceptualization of key phenomena important in the study of emotion—those phenomena that reflect functions and circuits related to survival, and that are shared by humans and other animals. The approach shifts the focus from questions about whether emotions that humans consciously feel are also present in other animals, and toward questions about the extent to which circuits and corresponding functions that are present in other animals (survival circuits and functions) are also present in humans. Survival circuit functions are not causally related to emotional feelings but obviously contribute to these, at least indirectly. The survival circuit concept integrates ideas about emotion, motivation, reinforcement, and arousal in the effort to understand how organisms survive and thrive by detecting and responding to challenges and opportunities in daily life.

Joseph LeDoux
Rethinking the Emotional Brain
Neuron, Volume 73, Issue 5, 8 March 2012, Page 1052

Neural development: Epigenetic regulation of asymmetry

The brains of many species demonstrate structural and functional bilateral asymmetry, yet the underlying molecular mechanisms are mostly unknown. In the Caenorhabditis elegans nervous system, the lineages arising from the two daughter cells of a particular blastomere known as ABarap produce a different cell on each side of the body: a motor neuron on the right and an epithelial cell on the left. Here, the authors show that the CAF-1 (chromatin assembly factor-1) protein complex, a histone chaperone that deposits histone H3 and H4 proteins onto replicating DNA, is required to establish this asymmetry, suggesting a role for epigenetic regulation in the generation of nervous system asymmetry.

Nature Reviews Neuroscience 13, 72 (February 2012) | doi:10.1038/nrn3183
IN BRIEF:Neural development: Epigenetic regulation of asymmetry
Katherine Whalley

Nakano, S. et al. 

Replication-coupled chromatin assembly generates a neuronal bilateral asymmetry in C. elegans. 

Cell 147, 1525–1536 (2011)

Scientists Prove Plausibility of New Pathway to Life's Chemical Building Blocks

For decades, chemists considered a chemical pathway known as the formose reaction the only route for producing sugars essential for life to begin, but more recent research has called into question the plausibility of such thinking. Now a group from The Scripps Research Institute has proven an alternative pathway to those sugars called the glyoxylate scenario, which may push the field of pre-life chemistry past the formose reaction hurdle.
Science Daily, Jan. 31, 2012

Vasudeva Naidu Sagi, et al.

Exploratory Experiments on the Chemistry of the “Glyoxylate Scenario”: Formation of Ketosugars from Dihydroxyfumarate. 

Journal of the American Chemical Society, 2012; : 120113151919003 DOI:10.1021/ja211383c

Scientists Discover New Clue to Chemical Origins of Life

Organic chemists at the University of York have made a significant advance towards establishing the origin of the carbohydrates (sugars) that form the building blocks of life.  A team led by Dr Paul Clarke at York has re-created a process which could have occurred in the prebiotic world.  They have made the first step towards showing how simple sugars -- threose and erythrose -- developed.   All biological molecules have an ability to exist as left-handed forms or right-handed forms. All sugars in biology are made up of the right-handed form of molecules and yet all the amino acids that make up the peptides and proteins are made up of the left-handed form. The researchers found using simple left-handed amino acids to catalyse the formation of sugars resulted in the production of predominately right-handed form of sugars. It could explain how carbohydrates originated and why the right-handed form dominates in nature.
Science Daily, Jan. 24, 2012

Laurence Burroughs, et al.

Asymmetric organocatalytic formation of protected and unprotected tetroses under potentially prebiotic conditions. 

Organic & Biomolecular Chemistry, 2012; DOI: 10.1039/C1OB06798B

Epigenetic understanding of gene-environment interactions in psychiatric disorders: a new concept of clinical genetics

Epigenetics is a mechanism that regulates gene expression independently of the underlying DNA sequence, relying instead on the chemical modification of DNA and histone proteins. Although environmental and genetic factors were thought to be independently associated with disorders, several recent lines of evidence suggest that epigenetics bridges these two factors. Epigenetic gene regulation is essential for normal development, thus defects in epigenetics cause various rare congenital diseases. Because epigenetics is a reversible system that can be affected by various environmental factors, such as drugs, nutrition, and mental stress, the epigenetic disorders also include common diseases induced by environmental factors. In this review, we discuss the nature of epigenetic disorders, particularly psychiatric disorders, on the basis of recent findings: 1) susceptibility of the conditions to environmental factors, 2) treatment by taking advantage of their reversible nature, and 3) transgenerational inheritance of epigenetic changes, that is, acquired adaptive epigenetic changes that are passed on to offspring. These recently discovered aspects of epigenetics provide a new concept of clinical genetics.

Takeo Kubota, Kunio Miyake and Takae Hirasawa

Clin Epigenetics. 2012; 4(1): 1.
Published online 2012 January 20. doi: 10.1186/1868-7083-4-1

Interneuron dysfunction in psychiatric disorders

Schizophrenia, autism and intellectual disabilities are best understood as spectrums of diseases that have broad sets of causes. However, it is becoming evident that these conditions also have overlapping phenotypes and genetics, which is suggestive of common deficits. In this context, the idea that the disruption of inhibitory circuits might be responsible for some of the clinical features of these disorders is gaining support. Recent studies in animal models demonstrate that the molecular basis of such disruption is linked to specific defects in the development and function of interneurons — the cells that are responsible for establishing inhibitory circuits in the brain. These insights are leading to a better understanding of the causes of schizophrenia, autism and intellectual disabilities, and may contribute to the development of more-effective therapeutic interventions.

Oscar Marín
Nature Reviews Neuroscience 13, 107-120 (February 2012) |doi:10.1038/nrn3155

Pattern separation in the hippocampus

The ability to discriminate among similar experiences is a crucial feature of episodic memory. This ability has long been hypothesized to require the hippocampus, and computational models suggest that it is dependent on pattern separation. However, empirical data for the role of the hippocampus in pattern separation have not been available until recently. This review summarizes data from electrophysiological recordings, lesion studies, immediate-early gene imaging, transgenic mouse models, as well as human functional neuroimaging, that provide convergent evidence for the involvement of particular hippocampal subfields in this key process. We discuss the impact of aging and adult neurogenesis on pattern separation, and also highlight several challenges to linking across species and approaches, and suggest future directions for investigation.

Michael A. Yassa, Craig E.L. Stark
Trends in Neurosciences, Volume 34, Issue 10, October 2011, Pages 515–525
http://dx.doi.org/10.1016/j.tins.2011.06.006, How to Cite or Link Using DOI

Epigenetics in C. elegans: Facts and challenges

Epigenetics is defined as the study of heritable changes in gene expression that are not accompanied by changes in the DNA sequence. Epigenetic mechanisms include histone post-translational modifications, histone variant incorporation, non-coding RNAs, and nucleosome remodeling and exchange. In addition, the functional compartmentalization of the nucleus also contributes to epigenetic regulation of gene expression. Studies on the molecular mechanisms underlying epigenetic phenomena and their biological function have relied on various model systems, including yeast, plants, flies, and cultured mammalian cells. Here we will expose the reader to the current understanding of epigenetic regulation in the roundworm C. elegans. We will review recent models of nuclear organization and its impact on gene expression, the biological role of enzymes modifying core histones, and the function of chromatin-associated factors, with special emphasis on Polycomb (PcG) and Trithorax (Trx-G) group proteins. We will discuss how the C. elegans model has provided novel insight into mechanisms of epigenetic regulation as well as suggest directions for future research.

Dirk Wenze et al.
genesis 49:647–661, 2011.