Monday, July 28, 2014

Canadian Team Discovers Master Gene for Motor Development

This illustration shows the cerebellum's location in the human brain. Illustration: Alan Hoffring, National Cancer Institute, public domain image.





A Canadian research team announced in 2014 they had discovered a master control gene - Snf2h - critical for development of the cerebellum. The cerebellum (Latin for or little brain) at the base of the skull coordinates muscle contractions for smooth movement, muscle tone at rest, and helping maintain balance.

About half your entire brain's neurons are found in the cerebellum; it's a tightly-packed twin-hemisphere hindbrain region, with much denser surface folds than the outer surface of the main brain - the cerebral cortex (Latin for brain bark). Its hundreds of millions of neurons primarily relay information between muscles of the body and motor control regions of the cerebral cortex. It acts as a comparator, using mismatches between intentions and actual movement as an error-correction guide to produce fine, complex movements - comparing mental motor control commands with actual movement to correct and refine motion. 

Most information about the cerebellum's function is derived from examining humans and animals with damage to the region. Subjects with cerebellar damage  suffer from major motor control problems, ipsilateral (on the opposite side of the body) to the damaged cerebellar lobe. While they can still produce movement, it is uncoordinated, mistimed, or erratic. Because of this and fMRI scans, it is believed the region fine tunes and coordinates, rather than initiates or selects movement.

However, recent findings indicate the cerebellum is not solely motor-related. It also activates during functions related to mental imagery, attention, motor learning and language.

The cerebellum also develops in response to external stimulation, so in response to practice, specific genes or gene groups get switched on and off, strengthening the circuits to consolidate and perfect complex tasks. Snf2h functions as a master coordinator, orchestrating this complex, ongoing process. Such master genes are called epigenetic (above the gene) regulators, and they adapt according to environmental cues such as diet or stress, then adjust which genes are switched on or off.

Dr. David Picketts of the Ottawa Hospital Research Institute and University of Ottawa led the team which discovered Snf2h along the chromatin (DNA strands) in the nuclei of the brain's neural stem cells. According to Dr. Picketts, master epigenetic regulators like Snf2h affect memory, behaviour and learning.  

Silencing Snf2h in developing mice embryos results in cerebella one-third the normal size, with consequent errors in walking, balance and coordinated movement. Such impairment, cerebellar ataxia, is common among sufferers of neurodegenerative diseases.

When cerebellar stem cells divide, en route to specializing as specific neurons, Snf2h determines which genes will be activated and which genes will be curled up inaccessibly along the DNA strands. Without its guidance, some vital genes remain inactivated, while others which hinder development remain switched on. The result is sparser neurons, which don't respond and adapt to external signals efficiently. Gene expression in the cerebellum becomes progressively more disorganized, leading to cerebellar ataxia and premature death for the afflicted.

Source: Researchers find gene critical for development of brain motor centre, News Release, June 20, 2014, Paddy Moore, Ottawa Hospital Research Institute

Sunday, July 27, 2014

The Oldest Primate Skeleton

An artistic rendering of Archicebus achilles' skeleton. Grey regions represent the fossilized bones found the specimen. Illustration: Mat Severson, Northern Illinois University

Researchers at Beijing's Chinese Academy of Sciences say the world's oldest known primate is a tiny, 55-million-year-old tree climber dubbed Archicebus achilles. 

A farmer discovered the creature's fossil last year in a quarry near Jingzhou City in central China. The site, now famous for its Eocene-era bird and fish fossils, had been an ancient lake. According to Dr. Xijun Ni, the region had once been covered in lush tropical forests and lakes.

Dr. Dan Gebo of Northern Illinois University says Archicebus is one of the earliest primates ever discovered, and its fossil is the most complete set from the Eocene Era ever recovered.

Archicebus was tiny, weighing under an ounce, with slender limbs and a long tail. Its anatomy was suited to leaping among the trees, feeding primarily upon insects during daylit hours. It seems to have been a hybrid, with the feet of a small monkey, the arms, legs and teeth of a much more primitive primate, and surprisingly tiny eyes.

The creature's name is derived from the Greek words Archi meaning "first" and cebus meaning "long-tailed monkey", while Achilles refers to the legendary Greek warrior with a special heel. This is because its most unusual features are in its feet, which combine strong big toes for grasping, long, nailed toes of ancient tree dwellers and monkey-like heel and metatarsals (innermost toe bones), advanced features not normally found among early Eocene primates. This unique blend of anatomical characteristics places it near the evolutionary split of tarsiers - tiny, nocturnal tree-dwellers - and anthropoids, the lineage which includes modern monkeys, apes, and humans.

Dr. Gebo believes that Archicebus and similar recent discoveries place the origin of primates in Asia, rather than Africa.

Source: Oldest primate skeleton discovered, press release, June 5th, 2013, Northern Illinois University

Thursday, July 24, 2014

Heisenberg's Uncertainty Principle

In 1687, Cambridge mathematics chairman Sir Isaac Newton published the Philosophiae Naturalis Principia Mathematica (Mathematical Principles of Natural Philosophy). It was a stunning achievement, destined to change the world forever. The Principia outlined the principles of classical mechanics - laws governing motion and gravity, including the motions of astronomical bodies, the tides, the progression of the seasons and general principles governing objects in motion.

The work would shape our view of the natural world for two and a half centuries. Its formulae describe an orderly universe, where objects follow strict, predictable laws of behavior with clockwork-like precision. The Principia helped usher in a new Age of Reason - a breathtakingly optimistic view that we could understand the deepest secrets of reality if we used the proper yardstick. For the first time in human history, we seemed to be the utter masters of the universe; incredibly complex phenomena like the movement of the planets and progression of the seasons could now be predicted using the simplest of mathematical formulae.

Then, in 1927, a brilliant young physics professor in Copenhagen released a paper that would rip away the illusion of comfortable predictably we had so long enjoyed. Matter, he demonstrated, acted in the strangest of ways.

With "On the Perceptual Content of Quantum Theoretical Kinematics and Mechanics" and subsequent writings, young Werner Heisenberg propelled the new field forward, helping physicists understand how stars ignite, why atoms don't implode, and that so-called "empty" space never truly is. His research would eventually net its author a Nobel Prize.

Over the previous ten years, renowned physicists like Heisenberg's mentor Neils Bohr and contemporary Erwin Schrodinger had been working out the principles of this new field of quantum theory, which explains the behavior of matter on a subatomic scale.

Heisenberg would go on to demonstrate that nature is inherently uncertain or "fuzzy", and that there are limits to what we can learn about quantum particles. At best, we can only calculate subatomic particle behavior and location in terms of probabilities. We would also learn that energy does not flow continuously, but instead takes the form of discrete packets called quanta, and these quanta can act like either a wave or a stream of particles, depending upon the way they are measured.

Heisenberg had discovered a problem with quantum particle measurement: we can measure either the position (x) or the momentum (p) of a subatomic particle with relative precision, but never both. In fact, the more precisely we determine one property, the less precisely we can measure the other.

Objects in the macroscopic world become visible when photons bounce off them and travel to retinal surfaces at the rear of your eyeballs. Here, a photon's energy stimulates a molecular change in a special protein called a rhodopsin, and when enough of these molecular changes accumulate, it stimulates a neural impulse that is delivered to the visual cortex of your brain.

However, to "see" the position of an electron or other subatomic particle, bouncing a photon against it may alter its path, making it impossible to precisely predict the direction in which it will travel. Similarly, an electron's rapid movement will change its position immediately after its measurement. In either case, either the position or the momentum will be inaccurately measured, disturbed by the very act of measuring it.

It's impossible to predict an electron's momentum and position with complete accuracy, so we speak of their orbits in terms of "probability clouds" - the likelihood that an electron will be in a certain area. In atoms, negatively-charged electrons orbit in "probability clouds" around a nucleus containing positively-charged protons.

Source: What is Heisenberg's Uncertainty Principle? Alok Jha, November 10, 2013, Guardian News and Media


Wednesday, July 23, 2014

The Passing of Neanderthal Man

An analysis of 40,000-year-old Neanderthal, human and animal bones suggests we outlived Neanderthals because of drastic climate change. Above, a wolf jaw fragment from Le Moustier, analyzed during an international study of Paleolithic-era European nitrogen isotope concentrations. Nitrogen isotopes increase in plants under arid conditions, which are then taken up by herbivores, who are in turn eaten by carnivores, passing the detectable isotopes upward through the food chain. Photo: Herve Bocherens, University of Tubingen


Approximately 40,000 years ago, the remarkably hardy, well-adapted and comparatively stronger species of hominids called the Neanderthals vanished virtually overnight, for reasons as yet shrouded in mystery. Analyses of skull brain cases show that, in addition to being physically stronger than modern humans, Neanderthals possessed a much larger occipital lobe, seat of the visual cortex. Therefore, in addition to superior strength and better physical adaptations to survive extreme cold, they likely had eyesight far superior to ours.

These factors make their abrupt disappearance from the archaeological record a remarkable mystery. Among the more unsettling possibilities, evidence suggests we might have eaten them. Less controversially, however, it's been posited that Homo sapiens' wider dietary tolerances meant a survival advantage over the Neanderthals. This theory seemed to have been borne out by chemical analyses of fossil hominid bones; human bones from the era are higher in nitrogen-heavy isotopes when compared with Neanderthal bones, pointing to a diet that included fish, as opposed to the Neanderthal big-game-meat diet, primarily mammoth and bison flesh.

The problem with these dietary studies is that they did not include the isotope content of the animals that were actually being consumed at the time. However, 2014 studies at Germany's Tubingen University and France's Musee national de Prehistoire focused on nitrogen isotopes in animal bones of the era - including those from carnivores such as prehistoric wolves, and ancient herbivores such as deer, bison, and horses.

The analyses show nitrogen isotopes increased dramatically throughout the food chain just as modern humans first began appearing in southwestern France. Because the sudden isotope increase in animals mirrors the one found in hominid bones from the same period, the territorial takeover by humans over Neanderthals isn't likely from simple dietary changes; instead, such a pervasive isotope increase appears to have arisen from major environmental change.

An arid environment is known to trigger increased nitrogen isotope concentrations in plants, and when those plants are consumed by herbivores, who are then eaten by predators, the isotopes circulate throughout the food web.

Because this surge in isotopic nitrogen coincides with the extinction of Neanderthals, it's believed that environmental changes like an increase in aridity may have pushed humans into a position of ascendancy in prehistoric European territories.

Source: Paleo diet didn't change? the climate did, News Release, March 17, 2014, Universitaet Tubingen
Note: This article is a copyright-protected excerpt from the 2014 revised edition of The Path Book I: Origins, to be published this September by Polyglot Studios, KK and available direct from this blog's author or on Amazon.com.

Tuesday, July 22, 2014

Cracking the Code - Common Mental Processing for Distance, Whether Spatial, Temporal or Social

With phrases such as "the distant future" or "a long meeting", we regularly use distance-related words to describe time; and in metaphors describing "close friends" or "distant cousins", we use them to describe our social relationships. Researchers now think they know why - these figures of speech are rooted in a shared computation system in our brains.

The human brain, it seems, uses the same neural centers and methods to conceptualize "nearness" in space, time and social relations.

Using fMRI scans, Dartmouth neuroscientists Thalia Wheatley, Carolyn Parkinson and Shari Liu discovered common focal points of brain activity among volunteers as they looked at photos of friends vs. those of acquaintances, at objects seen from close up vs. far away, and as they read passages which referred to the immediate future vs. the distant future.

Their results indicate that, for computational efficiency, the human brain uses a common neural code to represent space, time and social "distance". Objects, times and people who are considered "close" use one pattern of activity, while those which are considered "distant" activate a second.

This echoes theories proposed by cognitive linguists, who say that we speak of abstract relationships using physical expressions such as our "inner circle" because we think of these relationships in such terms.
The experiment also seems to bolster Construal Level Theory (CLT), which posits that any form of distance means the same thing mentally, whether it's distance from the present moment, or from a person's own subjective experience. Dr. Wheatley says this explains why we tend to talk about time and relationships using metaphors for physical distance - such metaphors mirror the neural processes occuring in our brains, as we consider space, time or degrees of social connection.

Co-author Dr. Parkinson believes this convenient multipurposing of the same neural network is an example of "exaptation", where an existing biological, neural or genetic function is co-opted - used in a new or expanded way. Primates long ago evolved a brain system for representing space, so rather than evolving a completely new system, she says, the existing one has expanded to also represent time, and later to represent social relationships.

All three perception systems - spatial, temporal and social - share the feature of egocentricity: space is understood as distance radiating outward with ourselves at the center; we also perceive ourselves to be at the center of the present moment, and at the center of a social network populated by people at varying distances from us. Objects are located at various directions and distances from us in physical space; events are perceived at various distances in the future or past; and people are mentally placed at various points within a social web, the perceived distance from us depending upon the strength of our mutual connections. In fact, says the team, only minor adaptations are required to adapt nearly any egocentric reference system to the brain's spatial perception system.

According to their studies, the right inferior parietal lobule (IPL) acts as a flexible hub, using a "parsimonious encoding of proximity to self in spatial, temporal, and social frames of reference".They add that the IPL evolved to represent one's body in space and to guide sensorimotor transformations - using mental coordinates of a target to create coordinate-based instructions for muscle activation patterns. As the network expanded during the human brain's evolution, this coordinate-tracking capacity was recycled to work in increasingly abstract manners - calculating the temporal and social "distance" of objects rather than physical distances.

The main activity was clustered within the right IPL, but this region is part of a larger neural network called the frontoparietal control network (FPCN). In addition to the Right IPL, the circuit they discovered also engages the right temporal parietal junction (TPJ). Together, these two regions cooperate to help generate one's unique sense of self. The right IPL seems to represent space radiating out from the self, while the right TPJ supports mental distinctions between one's self vs. others.

The FPCN also comprises two brain circuits called the Default Mode Network (DMN), which processes internally-directed thought, and the Dorsal Attention Network (DAN), which processes externally-directed thought. The network activated by the experiment extended into additional regions (the superior temporal, supramarginal and angular gyri), as well as a small cluster in the medial occipital lobe, the brain's primary vision-processing center. The medial (central) region of the occipital lobe activates when picturing images during distance comparisons.

The supplementary motor area (SMA) and inferior frontal gyrus (IFG) are also thought to play a part; since both participate in retrieving spatial locations from memory, they may be also participate in accessing temporal and social frames of reference.

For a primer on brain anatomy and neuroscience, I recommend the free publication entitled Brain Facts - a Primer on the Brain and Nervous System from the Society for Neuroscience

Neuroscience Online, from the University of Texas Medical School

The Brain from Top to Bottom, an Interactive Website about the Brain and Human Behavior by McGill University

Or any of dozens of free Open Courseware programs offered by the greatest universities in the world:

Of course, you can also order PDF or paperback versions of my books ;-)

Sources: Dartmouth study provides first evidence of common brain code for space, time, distance
press release, February 4, 2014, John Cramer, Dartmouth College 

A Common Cortical Metric for Spatial, Temporal, and Social Distance, C. Parkinson, S. Liu, T. Wheatley, Journal of Neuroscience, 2014; 34 (5): 1979 DOI: 10.1523/JNEUROSCI.2159-13.2014

"Metaphor, Exaptation and Harnessing", Janet Kwasniak, February 6, 2014, Neuro-patch blog

Old cortex, new contexts: re-purposing spatial perception for social cognition, C. Parkinson, S. Liu, T. Wheatley, Frontiers in human neuroscience, 2013; 7 PMID: 24115928

Note: This article is a copyright-protected excerpt from the 2014 revised edition of The Path Book I: Origins, to be published this September by Polyglot Studios, KK and available direct or on Amazon.com. 

Sunday, July 20, 2014

Brown U. Prof Pinpoints Brain's Multi-tasking Control Circuit

Image: MRI scans revealed short term "working" memory in action within the premotor cortex, as volunteers participated in an experiment to test data selection from working memory. Credit: Badre lab/Brown University
Cognitive scientists at Brown University in Rhode Island have tracked down which brain regions enable choosing from data stored in short term "working" memory. When one chooses to take an action, the brain selects from various data held in this working memory.

For example, imagine you're on the phone with a client at the office, and the receptionist buzzes you to say a group has arrived for a tour of the factory. Meanwhile, you have to send an email to a colleague to say you won't be able to join her for lunch. While you're wrapping up the call, the three demands upon your attention - your client, tour, lunch with a colleague - are held within your working memory; upon ending your call, you'll choose one and act upon it.

At this point, you're recruiting neural circuits running from a specific region withing your emotion-generating limbic system (a part of the striatum known as the caudate) and your brain's executive control center, the prefrontal cortex (in a specific region called the dorsal anterior premotor cortex).

Because of its color, the striatum takes its name from the Latin word for "striped", and the caudate means "tail shaped", because of its shape, which resembles a shrimp. The striatum uses dopamine as a sort of biochemical valve to regulate neural signaling. Dopamine generates positive sensations, a reward that reinforces learning.

For example, when you see a delicious piece of cake, or your best friend, a surge of dopamine allows for freer signal flow throughout your brain and nervous system, resulting in feelings of elation or energized excitement. These positive sensations are central to learning and behavior selection - if an experience feels good, you want to repeat it. The same reward channel is at work in nearly all animal life - even such comparatively primitive organisms as fruit flies.

The caudate comprises a major part of the striatum, and is involved in voluntary actions, memory, learning, sleep, and social interactions. Studies indicate it also appears to be central in OCD - obsessive compulsive
disorder, in which the sufferer attempts to banish repetitive, unwanted thought processes (obsessions) through ritualistic behaviors over which she has difficulty with self-control (compulsions). It is thought the caudaute and another key behavior-related region called the ACC serve as "error checking" circuits, alerting one to a "mistake" in one's thoughts or behavior.

"Dorsal" means "toward the spine", while anterior means "toward the forepart". The premotor area helps plan and coordinate motor activity - muscle contractions for movement. What this means is that choosing from options within working memory recruits some of the same neural circuits used in planning movement.

Brown University Drs. Badre, Chatham, and Frank, conducted a lab experiment upon 22 adults, using magnetic resonance imaging to monitor brain activity while the participants engaged in a working memory exercise. The team measured how quickly the volunteers were able to select data from within their working memory, a process the team dubbed "output gating".

According to Dr. Badre, our limited working memory allows us to hold onto small bits of particularly useful data while engaged in other tasks, at which point our brain engages in output gating or choosing upon which data we will act. Coupled with input gating - choosing what to hold in working memory - output gating enables us to continue along a given course of action, with the capacity to hold options for what to do afterwards.

Both input and output gating occur in different regions, but the experiment in question was concerned specifically with output gating - the choice of behavior. During the experiment, the subjects watched a character sequence comprised of either alphabetic letters or symbols called wingdings. At either the start or the end of the task, they were then given a number to indicate which character in the sequence and which group - either alphabetic or symbolic - was relevant. The group of wingdings was assigned the number 1, while the group of letters was assigned the number 2.

When the relevancy number came before the sequence, the subjects would input gate (select to remember) only letters, and then output gate the correct letter from the sequence held in their working memory. When the relevancy number came after the sequence, the subjects would need to "input gate" (select to remember) everything, meaning the real cognitive operations consisted of output gating, and they needed to hold more characters in their working memory.

Because of the difference in mental power required, the experiment required subjects to respond to an additional situation where "3" meant they had to remember everything they saw, whether the hint came before or after the sequence. In this way, brain activity could be monitored specifically during the input gating sequence and the output gating sequence.

The subjects were able to finish the tasks at a variety of speeds, which was understood in the experiment as the amount of cognitive work the task required. The slowest responses came when subjects had to respond to the relevancy number after the sequence and select a single specific symbol from memory (for example, after seeing a 1, choosing a wingding from the sequence).

The fastest responses came when subjects were given the relevancy number before the sequence and chose a specific symbol based upon the cue (for example, after seeing a 2, choosing a letter that would follow in the sequence).

MRI scans showed the caudate and dorsal anterior premotor cortex were significantly related to participant reaction times. Says Chatham, the striatum is central to gating the data, much like a traffic lights signal along a route, while the cortex interprets the context.

Source: Study reveals workings of working memory, Press Release, February 19, 2014, David Orenstein, Brown University

Wednesday, July 16, 2014

Stunning News: DNA Carries Two Codes - Simultaneously

A 3D model of yeast DNA, used to discover a second code embedded in DNA. Photo  Flickr/CC

It's becoming ever more apparent that in the world of genetics that things are much more complex than we initially believed. In addition to Yale's 2012 discovery that DNA is NOT in fact identical in each of an organism's cells, University of Washington researchers discovered in 2013 that there is DNA contains a second hidden code.

DNA's molecular structure was first deciphered in 1953 by Cambridge researchers Francis Crick and James D. Watson; since that time, scientists have believed the molecule only functioned as a cellular blueprint for synthesizing proteins.

However, UW Geneticist Dr. John Stamatoyannopoulos has announced the stunning discovery that DNA actually contains two separate languages - one to direct protein manufacture, and the other to tell a cell how to control its genes. Because one language is written atop the second, that second language long remained hidden.

According to Dr. Stamatoyannopoulos, scientists have believed for the past forty years that DNA code only affects how proteins are made, but this is only half the story. His team's new findings show DNA to be "...an incredibly powerful information storage device... which nature has fully exploited in unexpected ways.”

DNA uses an "alphabet" of 64 tiny sections called codons. The new research shows that some of these codons, dubbed duons, can carry two messages, one for the sequence of amino acid building blocks in a protein, and the second for controlling genes. Both functions appear to have arisen in tandem, with the instructions for gene control apparently helping to stabilize beneficial protein features and their synthesis.

Duons will mean a major difference in how patient gene sequences are interpreted, and will lead to new diagnoses and treatments of illnesses.

According to Dr. Stamatoyannopoulos, DNA's ability to convey two streams of data simultaneously means alterations which seem to change protein sequences might in fact underlie disease, disrupting programs that control gene functions, or perhaps gene functions and protein synthesis simultaneously, .

Dr. John Stamatoyannopoulos' research is part of an international collaboration in the massive ENCODE (Encyclopedia of DNA Elements Project), which is gradually decoding the molecular instructions behind the functions of the human genome.

Source: Scientists discover double meaning in genetic code, press release, December 12, 2013, Stephanie Seiler, University of Washington Health Sciences & University of Washington Medicine

Note: This article is a copyright-protected excerpt from the 2014 revised edition of The Path Book I: Origins, to be published this September by Polyglot Studios, KK and available direct or on Amazon.com. 

Tuesday, July 15, 2014

A Feathery Pedigree

Image: Scansor chick, Matt Martyniuk, 2014, creative commons attribution license 3.0
A feathered, finch-sized tree-climber that lived 164 million years ago in Liaoning, China may force a rewrite of the textbooks.

It has long been believed that modern birds evolved from ground-dwelling dinosaurs which had developed the power of flight. But Scansoriopteryx (Latin for "climbing wing"), wasn't a dinosaur - it came from a much more ancient lineage, and was a tiny tree-climbing creature with the ability to glide, much like modern flying squirrels.

According to University of North Carolina paleontologists Stephen Czerkas and Alan Feduccia, Scansoriopteryx had been mistakenly classified as a ground-dwelling theropod (Greek for "beast foot") dinosaur, from which experts thought flying dinosaurs and eventually birds evolved.

Using 3D microscopy, high resolution photography and special lighting to reveal never-before-seen features of the fossil, the team found that Scansoriopteryx "unequivocally lacks" the skeletal features of a dinosaur. They add that this is further evidence that birds are not descended from dinosaurs, but from much tree-climbing archosaurs (Latin for "ruling reptiles"), an ancient lineage that long predated the dinosaurs, and would eventually also evolve into the crocodilians.

The fossil contains feather imprints and shows that Scansoriopteryx had an elongated third finger, nearly twice as long as its second - most theropod dinosaurs have an elongated second finger. Its bird-like feet and claws had been adapted for an arboreal (tree-dwelling) lifestyle, optimized for climbing and perching.

Scansoriopteryx also had several other distinctly birdlike features, such as wing- and hindlimb feathers, long forelimbs, wing membranes distal (opposite) to its elbow, but, rather than flying, it would only have been capable of gliding or parachuting from trees.

Although Czerkas and Feduccia's conclusions have drawn skepticism, the discovery apparently bears out early 1900s predictions that evidence would show modern birds are derived from tiny, tree-dwelling archosaurs with feathers for gliding. This "trees down" view contrasts with the "ground up" view long held by many modern paleontologists who say birds evolved from ground-dwelling theropod dinosaurs.

Source: "Birdlike fossil challenges notion that birds evolved from ground-dwelling dinosaurs", press release, July 9, 2014, Springer Science and Business Media

Sunday, July 13, 2014

The Memory Switch

University of Bristol researchers have pinpointed the gene which initiates neural changes underlying memory storage in the human brain. Located on the short arm of the human X chromosome, the CASK gene contains instructions for a particular protein, found mainly in the brain's neurons, where it assists in regulating neurotransmitters and the movement of charged atoms called ions, critical for neuron-to-neuron signal transmission. Image: US National Institutes of Health

Our ability to learn and build memories hinges upon a long-term increase of efficiency in neural transmission, a process called Long Term Potentiation (LTP). In this state, the synapse (connection between two neurons) is made more sensitive to stimulation, and thus the post-synaptic (receiving) neuron is more likely to fire in the future.

The physical changes underlying this adaptation are controlled by a chemical chain reaction triggered when calcium enters a neuron, activating a key protein on-off switch called a kinase.

One major family of kinase switches are the calcium-activated Ca2+ responsive kinases (CaMKII). These protein switches help control critical life functions like muscle contraction, neurotransmitter release, stored energy (glycogen) use, and control of transcription factors - which jump-start the reading of our DNA's "blueprints" for protein manufacture.

When calcium activates CaMKII, the kinase "revs up" into an self-maintaining active state, even after the triggering calcium is gone. This self-maintaining activity is the brain's "molecular memory switch", and malfunctions have been linked to heart arrhythmia and Alzheimer’s disease.

In 2014, University of Bristol scientists used common fruit flies (Drosophila) to pin down the primary gene and molecule responsible for controlling the memory switch in the hippocampus, the primary memory and navigation center found deep within the human brain. Prior to this revolutionary discovery, the specific trigger for LTP had been a long-standing mystery.

Because Drosophila breeds and matures so quickly, it is very efficient to use as a model in studying biochemical processes. Drosophila also shares a great deal of common DNA with humans - over 60%, primarily the homeotic genes that direct embryonic growth according to a specific, symmetric body-plan.

Bristol Professor James Hodge and his colleagues used trial and error to suppress memory-related regions of fruit fly DNA until they pinpointed a specific region - a gene called CASK - the cellular blueprint for synthesizing the protein memory switch.

In humans, cellular DNA is bundled in tightly-wound, microscopic molecular strips called chromosomes. Of these, the X and Y chromosomes regulate the development of sexual characteristics in humans. The CASK gene is found on the short arm of the human X chromosome. It is a unique combination of 404,253 building blocks called nucleotides lined up and joined along a sugar-phosphate backbone molecule that, if stretched out, would be about two inches long.*

The CASK gene contains instructions for synthesizing the calcium/calmodulin-dependent serine protein kinase (CASK), a unique shuffling of 926 linked molecular building blocks (amino acids) found mainly in the brain's neurons, where it assists in regulating neurotransmitters and the movement of charged atoms called ions, critical for neuron-to-neuron signal transmission. It also helps control the protein-manufacturing activity (expression) of other genes involved in brain development. Mutated versions of the CASK gene have  previously been linked to several severe learning disorders.

Fruit flies can learn to search for food and to avoid painful stimuli just like any other complex animal, so Dr. Hodge's team tested the flies' learning and memory capacities using two separate odors. One smell would lead to food, and the other to a mild shock. They discovered that about 90 percent of the flies could learn to avoid the shocks after five trials, and the lesson would stay with each fly up to a week - a significant portion of their entire lifespan.

Switching off CASK and CaMKII production in Drosophila's memory centers caused the flies to be unable to remember to avoid the shock even three hours later. But replacing fruit fly CASK genes with the human version (which is 80 percent identical to Drosophila's) enabled specimens to learn normally again.
Says Dr Hodge, locating the CASK-CaMKII memory switch is a major first step in finding new treatments and drugs for stopping or even reversing the effects of memory loss.

Sources: "Scientists identify brain's 'molecular memory switch'", press release, March 28, 2013, University of Bristol
"Genes: CASK", 2011-2014, Genetics Home Reference, US National Institutes of Health
"Length of a Human DNA Molecule", The Physics Factbook, Glenn Eler, Steven Chen, et al
Please note that this material is a copyrighted excerpt from The Path: Origins

* interestingly, if all the DNA from your body's 1013 cells were stretched out into a single strand, it would be the equivalent of just over 133 AU - astronomical units - or 133 trips from the Earth to the Sun at its average annual distance of 149597870.7 kilometers or nearly 93 million miles.



Friday, July 11, 2014

If the Moon Were Only One Pixel - a Truly Humbling Map of the Solar System


Space is big. 


As in really, really, REEEAAAALLY big. How big?

Well, let's have a little looky loo.

Prepare yourself for a Hell of a lot of scrolling. This solar map is pretty amazing, because it really puts into perspective the distances between us and pretty much everything else in just our tiny corner of the Milky Way alone
.

By the way, there's a little "hidden" feature in there - a light speed button in the lower right! What's astounding is how SLOW light travels when it comes to the mind-bendingly huge distances of space! 


Thursday, July 10, 2014

Standing out from the (primate) crowd....

A newly-mapped, uniquely human region of the brain (shown in red). Image courtesy of Oxford University
In 2014, Oxford researchers pinpointed a human brain region unlike anything possessed by our nearest primate relatives. The region, located in the ventrolateral frontal cortex, is central to some of the highest-level decision-making and planning processes which distinguish humans from other primates. The ventrolateral frontal cortex, or vlFC, which is present only in humans and other primates, participates in several of the most complex cognitive and language-related operations.  

According to Oxford’s Dr. Matthew Rushworth, our unique cognitive flexibility, capacity to learn from others and ability to plan are particularly advanced, and likely derive from circuits in this region. 

To locate key parts of the vlFC, and to determine how these areas interact with other brain regions, Dr. Rushworth's team performed MRI scans upon 25 adult humans. After, the results were compared to MRI scans of equivalent regions in 25 macaque monkeys. 

The team found 12 functional areas within the human vlFC consistent among all the test subjects. Of these, 11 corresponded to areas in macaque brains, although interconnections within the vlFC itself varied between the two species. The team also discovered that the human prefrontal cortex was extensively connected to association areas in the temporal lobe - an area which processes auditory stimuli and language input and output - but significantly less so in macaque brains. They believe these connections are central to our capacity for understanding and generating speech.

Said Professor Rushworth in an Oxford press release, "Each of these 12 areas has its own pattern of connections with the rest of the brain, a sort of “neural fingerprint”, telling us it is doing something unique".

The team also found one additional distinctively human component: a region named the lateral frontal pole prefrontal cortex. Their experiments show the lateral frontal pole prefrontal cortex is central to the uniquely human abilities to multitask, to strategically plan, and to make option-weighted decisions.

Source: What makes us human?: Unique brain area linked to higher cognitive powers, Press Release, January 29, 2014, Oxford University 

Wednesday, July 9, 2014

Harvard finding refutes 160 years of neuroscience, may point to future human evolution

Image: A 3D computer image of three neurons, displaying differing myelination. Myelin, a fatty insulation around nerve axon (tail) segments, speeds up neural transmission significantly. Credit Daniel Berger and Giulio Tomassy/Harvard University.

This year, Harvard Drs. Paola Arlotta, Jeff Lichtman and Giulio Srubek Tomassy discovered something that refutes 160 years of neuroanatomy knowledge: it seems the fatty neural insulator myelin, long thought critical for fast impulse transmission through neural axons, is not ubiquitous.

Classic neuroscience teaches that myelin is distributed along axons in several myelinated segments separated by tiny myelin-free nodes. This was believed to be a universal principle, but the new findings prove the assumption to be wrong - neural axons don't have a universal myelin distribution.

According to Dr. Arlotta, myelin is a somewhat recent evolutionary innovation, and, despite its importance in the brain, the team was surprised to discover that some of our most complex neurons are less well-insulated with myelin than older, more primitive ones. Paradoxically, the further into the most evolved regions of the cerebral cortex that one explores, the less myelin is found. Neurons there have a previously unknown, intermittent myelin distribution - very short myelin-rich regions interspersed with long, myelin-free regions.

Lead author Dr. Tomassy suggests these myelin distributions might enable neurons to branch out and communicate with neighboring neurons. Since mylenated axons can't synapse, it's possible that long myelin gaps serve to synchronize responses across different neurons or to enhance neural communication. It's also possible that intermittent myelin fine-tunes electrical impulses being transmitted along axons, enabling more complex behaviors to emerge.

The findings mean the purpose of myelin is not completely understood. What's more, says Dr. Arlotta, because the most advanced, highly-evolved neurons use less myelin, this might point to our future evolution. Increased processing needs seem to be driving neural diversity and myelin alterations.

Source: Harvard researchers present new view of myelin, press release, April 18, 2014, B. D. Colen, Neuroscience News, Harvard University