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The Reticular Formation, Limbic System and Basal Ganglia

February 19, 2012 2 comments

The Reticular Formation

It’s a ‘diffuse net’ which is formed by nerve cells and fibers. It extends from the neuroaxis spinal cord through medulla, pons, midbrain, subthalamus, hypothalamus and thalamus (spinal cord is relayed superiorly to the cerebral cortex).

Many afferent and efferent pathways project in and out of the RF from most parts of the CNS. The main pathways through the RF is poorly defined and difficult to trace using silver stains. Reticular formation can be divided into three columns : median, medial and lateral columns.

Functions of the Reticular formation

1.   Control of skeletal muscles:

  • RF modulates muscle tone and reflex activities (via reticulospinal and reticulo bulbar tracts). It is important in controlling muscles of facial expression when associated with emotions.

2.   Control somatic and visceral sensation (influence can be excitatory or inhibitory)

3.   Control of autonomic nervous system

4.   Control of endocrine nervous system (hypothalamus and the pituitary)

5.   Influence on the biological clock (rhythm)

6.   The reticular activating system (arousal and level of consciousness are controlled by the RF)

Clinical note

When a person smiles for a joke, the motor control is provided by the RF on both side of the brain. The fibers from RF is separated from corticobulbar pathway (supply for facial muscles). If a patient suffers a stroke that involves corticobulbar fibers, he or she has facial paralysis on the lower part of the face, but is still able to smile symmetrically.

The Limbic System

 Limbic structures   Functions of the limbic system 
  1. Sub callosal, cingulated and parahippocampal gyri
  2. Hippocampal formation
  3. Amygdaloid nucleus
  4. Mammillary bodies
  5. Anterior thalamic nucleus
1. Influence the emotional behavior:a. Reaction to fear and angerb. Emotions associated with sexual behavior

2. Hippocampus is involved in converting short term memory to long term memory (If the hippocampus is damaged, patient is unable to store long term memory – Anterograde amnesia)

The  Basal Ganglia and their connections

Connections of the Basal Ganglia

Yellow arrow : Pallidofugal fibers

Caudate nucleus and the Putamen: main sites of receiving inputs

Globus pallidus: main site from which output leaves

Afferent and Efferent fibers

Connections of the caudate nucleus and Putamen Connections of the Globus pallidus
Afferent Efferent Afferent Efferent
CS: CorticostriateTS: Thalamostriate

NS: Nigrostriate

BS: Brainstem striatal fibers

SP: Striatopallidalfibers

SN: Striatonigral fibers

SP: Striatopallidalfibers Pallidofugalfibers

Functions of  the Basal Nuclei

Basal Nuclei controls muscular movements by influencing the cerebral cortex (it doesn’t have direct control through descending pathways to the brainstem and spinal cord). It helps to prepare for the movements (enables the trunk and limbs to be placed in appropriate positions before discrete movements of the hands and feet).

Functional connections of the Basal Nuclei and how they influence muscle activities

 
REFERENCES: 
1. Ben Greenstein, Ph.D, Adam Greenstein, BSc (Hons) Mb, ChB Color Atlas of Neuroscience
2. Allan Siegel Ph.D, Hreday N. Sapru Ph.D Essential Neuroscience, 1st Edition
3. Stanley Jacobson, Elliot M. Marcus Neuroanatomy for the Neuroscientist
4. Patrick f. Chinnery Neuroscience for Neurologists
5. Dale Purves Neuroscience, 3rd Edition
6. Suzan Standring Gray’s Anatomy
7. Keith L. Moore, Arthur F. Dalley, Anne M. R. Agur Clinically Oriented Anatomy
8. Frank H. Netter Atlas of Human Anatomy
9. Walter J. Hendelman, M.D., C.M. Atlas of Functional Neuroanatomy
10. Mark F. Bear, Barry W. Connors, Michael A. Paradiso Neuroscience Exploring the Brain
11. Dale Purves et al. Principles of Cognitive Neuroscience
12. Eric R. Kandel et al. Principles of Neural Science

Right And Left Brain

February 17, 2012 1 comment

The brain is divided physically into a left and right half is not a new discovery. The Egyptians knew that the left side of the brain controlled and received sensations from the right side of the body and vice versa.

It is only in the last two dozen years, however, that the true implication of the left/right split has gradually become apparent, through the work of a number of researchers. The most famous are probably Dr.  Roger Sperry and Dr. Robert Ornstein of the California Institute of Technology. Their work has won them a Nobel prize.

Sperry and Ornstein noted that the left and the rig hemispheres are connected by an incredibly complex  network of up to 300 million nerve fibres called the Corpus callosum. They were also able to show that the two halves of the brain tend to have different functions.

They (and other researchers) indicate that the left brain primarily appears to deal with language and mathematical processes and logical thought, sequences, analysis and what we generally label academic  pursuits. The right brain principally deals with music, and visual impressions, pictures, spatial patterns, and colour recognition. They also ascribe to the right brain the ability to deal with certain kinds of conceptual   thought – intangible ‘ideas’ such as love, loyalty, beauty.

The specialization of the two halves of the brain can result in some bizarre behaviour. Patients who, for medical reasons, have had their Corpus callosum  severed,  have effectively two semi-independent brains: two minds in one head.

If a ball is shown to the left visual field of such a person, i.e. registered to their right brain hemisphere, the speaking half of the brain, which is in the other, (left) brain will claim to have seen nothing. If, however, the patient is asked to feel in a bag of assorted shapes he will correctly pull out a ball. If he is asked what he has done he will say ‘nothing’. The ball has only been seen with the right brain, and felt with the right brain. The speech centre, which is located in the left brain, has registered nothing.

Even more delicate experiments have been performed on surgically split-brained patients. The word SINBAD was projected to such a patient while his eyes were focused on the precise spot between N and B. The first 3 letters went to his right brain, the last three to his left hemisphere. When asked to saywhat he had seen, he replied BAD. When asked to point with his left hand to what he had seen he pointed to the word SIN.

The specialisation of the two brains  has also been demonstrated by measuring the electrical activity of the brain during various activities.

When the brain is relaxed in a state of rest, it tends predominantly to show an alpha brain wave rhythm – i.e. 8-12 Hz waves. Ornstein found that a subject tackling a mathematical problem showed an increase in alpha in the right hemisphere. This indicated that the right side was relaxing whilst the left was active and, therefore, in a beta brain wave pattern. In contrast, when a subject was matching coloured patterns, the left showed alpha (i.e. was resting) and the right showed beta (i.e. was active). More on brain waves can be found here.

The brain scans, show the varying levels of electrical brain activity in a subject listening to music, words and singing. The first activity (music) involved the right brain. The second (listening to words only) involved the  left brain, but singing (words and music together) involved the whole brain.

The left brain is now thought to be the half that specialises in serial, sequential thought, i.e. analysing  information in sequence in a ”logical” step by step approach. The left rationalises. The right brain seems to take in several bits of information ”at a glance” and process them into one overall thought. The right synthesises.

To read more click on this link to the full article: Right and Left Brain

Descending Tracts

February 17, 2012 Leave a comment

Descending tracts have three neurons:

1.   1st order neurons (UMN): cell bodies are in the cerebral cortex and other supra spinal areas

2.   2nd order neurons: short and situated in the anterior grey column of the spinal cord

3.  3rd  order neuron (LMN): situated in the anterior grey column and innervate the skeletal muscles through anterior roots of the spinal nerves

Corticospinal tract: rapid, skilled and voluntary movements

1st order neuron

Axons arise from the pyramidal cells of the cerebral  cortex  (situated  in  the  5th   layer),  2/3 from the pre central gyrus and 1/3 from the post central gyrus:

1. 1/3 of fibers arise from the 1stry motor  cortex (Area 4)

2. 1/3 of fibers arise from the 2ndry motor cortex (Area 6)

3. 1/3 of fibers arise from the parietal lobe

(Area 1, 2 and 3).

Descending fibers converge in the corona radiata and  pass  though  the   posterior  limb  of  the internal capsule; organization of fibers within the internal capsule:

1. close to genu (medial): concerned with the cervical parts of the body

2. away from the genu (lateral): concerned with the lower extremity.

The tract then passes through the middle 3/5 of the basis pedunculi of the midbrain; organization of fibers in the midbrain:

    1. medially: cervical parts of the body
    2. laterally: lower limbs.

When the tract enters the pons, it’s broken into many bundles by the transverse pontocerebellar fibers. In the medulla oblongata, the bundles group together to form the pyramids. At the junction of the MO and the spinal cord, most fibers cross the midline at the decussation of the pyramids and enter the lateral white column of the spinal cord to form the lateral corticospinal tract (LCST). LCST descends length of the spinal cord and terminates in the anterior grey column of all the spinal segments.

The fibers which didn’t cross, descend in the anterior white column of the spinal cord as the anterior corticospinal tract (ACST). Fibers of the ACST eventually cross and terminate in the anterior grey column of the spinal cord segments in the cervical and upper thoracic regions.

2nd order neuron:

It’s an internuncial neuron.

3rd order neuron:

It’s a alpha or gamma motor neuron.

To read more click on this link to the full article: Descending Tracts

Clinical Syndromes, Laboratory Diagnosis and Treatment of Orthomyxoviruses

February 12, 2012 3 comments

Clinical Syndromes

Depending on the degree of immunity to the infecting strain of virus and other factors, infection may range from asymptomatic to severe. Patients with underlying cardiorespiratory disease, people with immune deficiency (even that associated with pregnancy), the elderly, and smokers are more prone to have a severe case.

After an incubation period of 1 to 4 days, the “flu syndrome” begins with a brief prodrome of malaise and headache lasting a few hours. The prodrome is followed by the abrupt onset of fever, chills, severe myalgias, loss of appetite, weakness and fatigue, sore throat, and usually a nonproductive cough. The fever persists for 3 to 8 days, and unless a complication occurs, recovery is complete within 7 to 10 days. Influenza in young children (under 3 years) resembles other severe respiratory tract infections, causing bronchiolitis, croup, otitis media, vomiting, and abdominal pain, accompanied rarely by febrile convulsions (Table 1). Complications of influenza include bacterial pneumonia, myositis, and Reye syndrome. The central nervous system can also be involved. Influenza B disease is similar to influenza A disease.

Influenza may directly cause pneumonia, but it more commonly promotes a secondary bacterial superinfection that leads to bronchitis or pneumonia. The tissue damage caused by progressive influenza virus infection of alveoli can be extensive, leading to hypoxia and bilateral pneumonia. Secondary bacterial infection usually involves Streptococcus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus. In these infections, sputum usually is produced and becomes purulent.

Although the infection generally is limited to the lung, some strains of influenza can spread to other sites in certain people. For example, myositis (inflammation of muscle) may occur in children. Encephalopathy, although rare, may accompany an acute influenza illness and can be fatal. Postinfluenza encephalitis occurs 2 to 3 weeks after recovery from influenza. It is associated with evidence of inflammation but is rarely fatal.

Reye syndrome is an acute encephalitis that affects children and occurs after a variety of acute febrile viral infections, including varicella and influenza B and A diseases. Children given salicylates (aspirin) are at increased risk for this syndrome. In addition to encephalopathy, hepatic dysfunction is present. The mortality rate may be as high as 40%.

Laboratory Diagnosis

The diagnosis of influenza is usually based on the characteristic symptoms, the season, and the presence of the virus in the community. Laboratory methods that distinguish influenza from other respiratory viruses and identify its type and strain confirm the diagnosis (Table 2).

Influenza viruses are obtained from respiratory secretions. The virus is generally isolated in primary monkey kidney cell cultures or the Madin-Darby canine kidney cell line. Nonspecific cytopathologic effects are often difficult to distinguish but may be noted within as few as 2 days (average, 4 days). Before the cytopathologic effects develop, the addition of guinea pig erythrocytes may reveal hemadsorption (the adherence of these erythrocytes to HA-expressing infected cells). The addition of influenza virus-containing media to erythrocytes promotes the formation of a gel-like aggregate due to hemagglutination. Hemagglutination and hemadsorption are not specific to influenza viruses, however; parainfluenza and other viruses also exhibit these properties.

More rapid techniques detect and identify the influenza genome or antigens of the virus. Rapid antigen assays (less than 30 min) can detect and distinguish influenza A and B. Reverse transcriptase polymerase chain reaction (RT-PCR) using generic influenza primers can be used to detect and distinguish influenza A and B, and more specific primers can be used to distinguish the different strains, such as H5N1. Enzyme immunoassay or immunofluorescence can be used to detect viral antigen in exfoliated cells, respiratory secretions, or cell culture and are more sensitive assays. Immunofluorescence or inhibition of hemadsorption or hemagglutination (hemagglutination inhibition [HI]) with specific antibody can also detect and distinguish different influenza strains. Laboratory studies are primarily used for epidemiologic purposes.

To read more click on this link to the full article: Clinical Syndromes, Laboratory Diagnosis and Treatment of Orthomyxoviruses

Notre Dame researchers report fundamental malaria discovery

February 11, 2012 1 comment

A team of researchers led by Kasturi Haldar and Souvik Bhattacharjee of the University of Notre Dame’s Center for Rare and Neglected Diseases has made a fundamental discovery in understanding how malaria parasites cause deadly disease.

The researchers show how parasites target proteins to the surface of the red blood cell that enables sticking to and blocking blood vessels. Strategies that prevent this host-targeting process will block disease.

The research findings appear in the Jan. 20 edition of the journal Cell, the leading journal in the life sciences. The study was supported by the National Institutes of Health.

Malaria is a blood disease that kills nearly 1-3 million people each year. It is caused by a parasite that infects red cells in the blood. Once inside the cell, the parasite exports proteins beyond its own plasma membrane border into the blood cell. These proteins function as adhesins that help the infected red blood cells stick to the walls of blood vessels in the brain and cause cerebral malaria, a deadly form of the disease that kills over half a million children each year.

In all cells, proteins are made in a specialized cell compartment called the endoplasmic reticulum (ER) from where they are delivered to other parts of the cell. Haldar and Bhattacharjee and collaborators Robert Stahelin at the Indiana University School of Medicine – South Bend (who also is an adjunct faculty member in Notre Dame’s Department of Chemistry and Biochemistry), and David and Kaye Speicher at the University of Pennsylvania’s Wistar Institute discovered that for host-targeted malaria proteins the very first step is binding to the lipid phosphatidylinositol 3-phosphate, PI(3)P, in the ER.

This was surprising for two reasons. Previous studies suggested an enzyme called Plasmepsin V that released the proteins into the ER was also the export mechanism. However, Haldar, Bhattacharjee and colleagues discovered that binding to PI(3)P lipid which occurs first is the gate keeper to control export and that export can occur without Plasmepsin V action. Further, in higher eukaryotic cells (such as in humans), the lipid PI(3)P is not usually found within the ER membrane but rather is exposed to the cellular cytoplasm.

Haldar and Bhattacharjee are experts in malaria parasite biology and pathogenesis. Stahelin is an expert in PI(3)P lipid biology, and David and Kaye Speicher are experts in proteomics and a method called mass spectrometry.

Story Source:

The above story is reprinted (with editorial adaptations by MedicalXpress staff) from materials provided by University of Notre Dame (news : web)

Ascending Tracts

February 10, 2012 Leave a comment

Introduction

They are located in the white matter and conduct afferent information (may or may not reach consciousness). There are two types of information:

  1. Exteroceptive : originates from outside the body (pain, temperature and touch
  2. Proprioceptive : originates from inside the body (from muscles and joints)

Normally there are three neurons in an ascending pathway:

  1. 1st order neuron: cell body is in the posterior root ganglion
  2. 2nd  order neuron: decussates (crosses to the opposite side) and ascends to a higher level of the    CNS
  3. 3rd neuron: located in the thalamus and passes to a sensory region of the cortex

Pain and temperature pathway: lateral spinothalmic tract

1st order neuron

Peripheral process extends to skin or other tissues and ends as free nerve endings (receptors). Cell body is situated in the posterior root ganglion. Central process extends into the posterior grey column and synapses with the 2nd order neuron.

2nd order neuron

The axon crosses obliquely to the opposite side in the anterior grey and white commissures within one spinal segment of the cord. It ascends in the contralateral white column as the lateral spinothalamic tract (LSTT).

As the LSTT ascends through the spinal cord new fibers are added to the anteromedial aspect of the tract (sacral fibers are lateral and cervical fibers are medial). The fibers carrying pain are situated anterior to those conducting temperature.

As the LSTT ascends through the medulla oblongata,  it’s  joined  by  the  anterior spinothalamic tract and the spinotectal tract and forms the spinal lemniscus. Spinal lemniscus ascends through the pons and the mid brain.

Fibers of the LSTT end by synapsing with the 3rd order  neurons  in  the  ventral  posterolateral nucleus  of  the  thalamus  (here  crude  pain  and temperature sensations are appreciated).

3rd order neuron

Axons pass through the posterior limb of the internal capsule and corona radiata  to reach the somatosensory  area  in  the  post  central  gyrus  of  the  cerebral  cortex.  From  here  information is transmitted to other regions of the cerebral cortex to be used by motor areas. The role of the cerebral  cortex  is  interpreting  the  quality  of  the  sensory  information  at  the  level  of  the consciousness.

Light (crude) touch and pressure pathway: anterior spinothalamic tract (ASTT)

1st order neuron

It is similar to the pain and temperature pathway.

2nd order neuron

The axon crosses obliquely to the opposite side in the anterior grey and white commissures within several spinal segments. It ascends in the contralateral white column as the anterior spinothalamic tract (ASTT). As the ASTT ascends through the spinal cord new fibers are added to the anteromedial aspect of the tract (sacral fibers are lateral and cervical fibers are medial).

As the ASTT ascends through the medulla oblongata, it’s joined by the lateral spinothalamic tract and the spinotectal tract and forms the spinal lemniscus. Spinal lemniscus ascends through the pons and the midbrain. Fibers of the ASTT end by synapsing with the 3rd order neurons in the ventral posterolateral nucleus of the thalamus (here crude awareness of touch and pressure sensations are appreciated).

3rd order neuron

Axons pass through the posterior limb of the internal capsule and corona radiata to reach the somatosensory area in the post central gyrus of the cerebral cortex. The sensations can be crudely localized. Very little discrimination is possible.

To read more click on this link to the full article: Ascending Tracts (pdf).

Brain Waves

February 10, 2012 3 comments

Introduction Brain waves

The brain generates tiny electrical pulses as The brain produces four main waves with thoughts traverse the labyrinth of the mind. The specific frequencies:

physical conduits of these thoughts are the millions of nerve cells or neurons in the brain. Just as radio signals, in order to make a comprehensible message, are beamed out on radio waves, a band of signals within a defined frequency, so the brain’s activity also occurs in waves. Brain waves can be measured on an electro-encephalograph machine (which is normally abbreviated to EEG Machine). By attaching sensitive electrodes to the scalp, it is possible to measure accurately the type of brain wave that a subject is producing. These waves are usually expressed in the number of cycles per second (CPS) or with their frequency (Hz).

1. Beta level brain waves – range 12-16 Hz (also 13-25 Hz)

2. Alpha level brain waves – range 8-12 Hz 3. Theta level brain waves – range 4-7 Hz
4. Delta level brain waves – range 0.5-3 Hz

The following chart relates each type of brain wave to its principal function. We must remember however, that when we speak of someone being ‘in alpha’ we mean that this is their characteristic and predominant brain wave. Other brain waves will also be present, but in smaller quantities than usual.

Brain activities

The linking of left and right brain activities is important in producing a shift from learning to accelerated learning. Yet our society is very ‘beta orientated’. We are busy thinking about the problem in hand, but don’t leave ourselves sufficiently open to other influences, which would help us memorize faster and make the sort of less expected connections that we call creative thinking.

Beta brain

In beta you don’t see the wood for concentrating on the trees. But learn to relax, increase the proportion of the alpha and ideally theta brain waves, and you have created the conditions where you may begin to see the whole picture.

Alpha brain

‘Alpha’ is a natural and receptive state of mind, that we can all attain through the techniques of relaxation. They principally involve simple and pleasant relaxation exercises and listening to certain types of music.

Theta brain

The theta brain wave pattern is especially interesting. It occurs spontaneously to most of us in the twilight state between being fully awake and falling asleep. Arthur Koestler called it ‘reverie’. This drowsy stage is associated with fleeting semi-hallucinatory images. Thousands of artistic and literary inspirations and scientific inventions have been credited to this state, a sort of freeform thinking that puts you in touch with your subconscious.

Brain waves interpretation

Many psychologists would agree it is a reasonable hypothesis that, when left/right brain symbiosis takes place, conscious and subconscious are also united. The proportion of theta brain waves becomes much higher than normal. This is the moment when logical left brain activity declines. The left brain, which normally acts as a filter or censor to the subconscious, drops its guard, and allows the more intuitive, emotional and creative depths of the right brain to become increasingly influential.

If the hypothesis is true, then do women, popularly characterised as more intuitive, reach a walking theta state more often than men; and can this be associated with the fact that their left/right brain link, the Corpus callosum, is larger and richer in connective capabilities than men’s? We do not yet know, but it is a fascinating area for future research.

At the University of Colorado Medical Centre and at the Biofeedback Centre in Denver, Dr. Thomas Budzyski has found that, when people were trained to achieve and maintain theta brain waves using biofeedback techniques, they did indeed learn much faster. Moreover, many emotional and attitudinal problems were solved at the same time.

To read more click on this link to the full article: Brain Waves (pdf).

Debating research into mutant H5N1 flu virus

February 8, 2012 1 comment

On 2 February, scientists and public health officials squared off in a panel discussion at the New York Academy of Sciences. At stake, the fate of two papers which describe a mutant strain of the avian influenza virus H5N1. The virus is capable of mammal-to-mammal transmission, which has raised concern that it might be transferable to humans. Several panelists sat down with Nature News to discuss their positions prior to the panel discussion.

For more on the NYAS debate, visit Nature’s blog:

http://blogs.nature.com/news/2012/02/emotion-runs-high-at-h5n1-debate.html

and see web special about the ongoing controversy over H5N1:

http://www.nature.com/news/specials/mutantflu/index.html

Or see NYAS.org where the NYAS has posted two hours of video from the H5N1 event. Now everyone can see exactly what Mike Osterholm said to Peter Palese. Highly unprofessional, in my opinion, and not conducive with a good scientific discourse. Laurie Garrett was not much better.

“Dual Use Research: H5N1 Influenza Virus and Beyond” Panel Sparks Lively Debate | The New York Acade

Making memories last: Prion-like protein plays key role in storing long-term memories

February 7, 2012 Leave a comment

(left) Drosophila Orb2 plays an important role in the persistence of memory. Upon stimulation, Orb2 (shown in yellow) forms amyloid-like oligomers (shown in red), which are an essential ingredient for the formation of long-term memory. Credit: Illustration: Nicolle Rager Fuller, Sayo-Art

Memories in our brains are maintained by connections between neurons called “synapses”. But how do these synapses stay strong and keep memories alive for decades? Neuroscientists at the Stowers Institute for Medical Research have discovered a major clue from a study in fruit flies: Hardy, self-copying clusters or oligomers of a synapse protein are an essential ingredient for the formation of long-term memory.

The finding supports a surprising new theory about memory, and may have a profound impact on explaining other oligomer-linked functions and diseases in the brain, including Alzheimer’s disease and prion diseases.

“Self-sustaining populations of oligomers located at synapses may be the key to the long-term synaptic changes that underlie memory; in fact, our finding hints that oligomers play a wider role in the brain than has been thought,” says Kausik Si, Ph.D., an associate investigator at the Stowers Institute, and senior author of the new study, which is published in the January 27, 2012 online issue of the journal Cell.

Si’s investigations in this area began nearly a decade ago during his doctoral research in the Columbia University laboratory of Nobel-winning neuroscientist Eric Kandel. He found that in the sea slug Aplysia californica, which has long been favored by neuroscientists for memory experiments because of its large, easily-studied neurons, a synapse-maintenance protein known as CPEB (Cytoplasmic Polyadenylation Element Binding protein) has an unexpected property.

A portion of the structure is self-complementary and—much like empty egg cartons—can easily stack up with other copies of itself. CPEB thus exists in neurons partly in the form of oligomers, which increase in number when neuronal synapses strengthen. These oligomers have a hardy resistance to ordinary solvents, and within neurons may be much more stable than single-copy “monomers” of CPEB. They also seem to actively sustain their population by serving as templates for the formation of new oligomers from free monomers in the vicinity.

CPEB-like proteins exist in all animals, and in brain cells they play a key role in maintaining the production of other synapse-strengthening proteins. Studies by Si and others in the past few years have hinted that CPEB’s tendency to oligomerize is not merely incidental, but is indeed essential to its ability to stabilize longer-term memory. “What we’ve lacked till now are experiments showing this conclusively,” Si says.

In the new study, Si and his colleagues examined a Drosophila fruit fly CPEB protein known as Orb2. Like its counterpart in Aplysia, it forms oligomers within neurons. “We found that these Orb2 oligomers become more numerous in neurons whose synapses are stimulated, and that this increase in oligomers happens near synapses,” says lead author Amitabha Majumdar, Ph.D., a postdoctoral researcher in Si’s lab.

The key was to show that the disruption of Orb2 oligomerization on its own impairs Orb2’s function in stabilizing memory. Majumdar was able to do this by generating an Orb2 mutant that lacks the normal ability to oligomerize yet maintains a near-normal concentration in neurons. Fruit flies carrying this mutant form of Orb2 lost their ability to form long-term memories. “For the first 24 hours after a memory-forming stimulus, the memory was there, but by 48 hours it was gone, whereas in flies with normal Orb2 the memory persisted,” Majumdar says.

Si and his team are now following up with experiments to determine for how long Orb2 oligomers are needed to keep a memory alive. “We suspect that they need to be continuously present, because they are self-sustaining in a way that Orb2 monomers are not,” says Si.

The team’s research also suggests some intriguing possibilities for other areas of neuroscience. This study revealed that Orb2 proteins in the Drosophila nervous system come in a rare, highly oligomerization-prone form (Orb2A) and a much more common, much less oligomerization-prone form (Orb2B). “The rare form seems to be the one that is regulated, and it seems to act like a seed for the initial oligomerization, which pulls in copies of the more abundant form,” Si says. “This may turn out to be a basic pattern for functional oligomers.”

The findings may help scientists understand disease-causing oligomers too. Alzheimer’s, Parkinson’s and Huntington’s disease, as well as prion diseases such as Creutzfeldt-Jakob disease, all involve the spread in the brain of apparently toxic oligomers of various proteins. One such protein, strongly implicated in Alzheimer’s disease, is amyloid beta; like Orb2 it comes in two forms, the highly oligomerizing amyloid-beta-42 and the relatively inert amyloid-beta-40. Si’s work hints at the possibility that oligomer-linked diseases are relatively common in the brain because the brain evolved to be relatively hospitable to CPEB proteins and other functional oligomers, and thus has fewer mechanisms for keeping rogue oligomers under control.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Stowers Institute for Medical Research press release

Original Research: Abstract for “Critical Role of Amyloid-like Oligomers of Drosophila Orb2 in the Persistence of Memory” by Amitabha Majumdar, Wanda Colón Cesario, Erica White-Grindley, Huoqing Jiang, Fengzhen Ren, Mohammed “Repon” Khan, Liying Li, Edward Man-Lik Choi, Kasthuri Kannan, Fengli Guo, Jay Unruh, Brian Slaughter, and Kausik Si in Cell


Right hand or left? How the brain solves a perceptual puzzle

February 7, 2012 Leave a comment

When you see a picture of a hand, how do you know whether it’s a right or left hand? This “hand laterality” problem may seem obscure, but it reveals a lot about how the brain sorts out confusing perceptions. Now, a study which will be published in a forthcoming issue of Psychological Science, a journal published by the Association for Psychological Science, challenges the long-held consensus about how we solve this problem. “For decades, the theory was that you use your motor imagination,” says Shivakumar Viswanathan, who conducted the study with University of California Santa Barbara colleagues Courtney Fritz and Scott T. Grafton. Judging from response times, psychologists thought we imagine flipping a mental image of each of our own hands to find the one matching the picture. These imagined movements were thought to recruit the same brain processes used to command muscles to move—a high-level cognitive feat.

The study, however, finds that the brain is adept at decoding a left or right hand without these mental gymnastics. Judging laterality is “a low-level sensory problem that uses processes that bring different senses into register”— a process called binding, says  Viswanathan. Seeing a hand of unknown laterality leads the brain to bind the seen hand to the correct felt hand. If they are still out of register because of their conflicting positions, an illusory movement arises from the brain’s attempt to bring the seen and felt hand into the same position. But “this feeling of moving only comes after you already know which hand it is.”

In the study, participants couldn’t see their own hands, which were held palm down. They saw hand shapes tilted at different angles, with a colored dot on them indicating a palm-up or down posture. One group of participants saw the shape first and then the dot; and the other, the dot first. Participants in both groups put the shape and dot together mentally and indicated which hand it was by pushing a button with that hand. However, when the shape and dot were shown simultaneously, participants in the first group felt movements of their right hands when seeing a left hand and vice versa; the other group always felt a movement of the correct hand. This behavioral difference (which experimenters gleaned from response time) was due to differences in participants’ perception of the seen hand—establishing that an earlier sensory process made the decision.

In a second experiment, participants were told which hand it was and had to judge whether its palm was down or up, indicating their answer with one hand only. This time, the illusory hand-movement occurred only when the seen hand-shape matched that of the participant’s own palm-down responding hand, but not otherwise. Even though no right/left judgments were required, the response was dominated by an automatic binding of the seen and felt hands, and the illusory movement followed, says Viswanathan.

The study helps us understand the experience of amputees, who sometimes sense an uncontrollable itch or clenching in the “phantom” body part. Showing the opposite hand or leg in a mirror allows the patient to “feel” the absent limb and mentally relieve the discomfort—a “binding” of vision and feeling.

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The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Association for Psychological Science (news : web).