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Archive for May 2008

Computing Brain’s Representation Of Meaning

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Scientists at Carnegie Mellon University have taken an important step toward understanding how the human brain codes the meanings of words by creating the first computational model that can predict the unique brain activation patterns associated with names for things that you can see, hear, feel, taste or smell.

Researchers previously have shown that they can use functional magnetic resonance imaging (fMRI) to detect which areas of the brain are activated when a person thinks about a specific word. A Carnegie Mellon team has taken the next step by predicting these activation patterns for concrete nouns — things that are experienced through the senses — for which fMRI data does not yet exist.

The work could eventually lead to the use of brain scans to identify thoughts and could have applications in the study of autism, disorders of thought such as paranoid schizophrenia, and semantic dementias such as Pick’s disease.

The team, led by computer scientist Tom M. Mitchell and cognitive neuroscientist Marcel Just, constructed the computational model by using fMRI activation patterns for 60 concrete nouns and by statistically analyzing a set of texts totaling more than a trillion words, called a text corpus. The computer model combines this information about how words are used in text to predict the activation patterns for thousands of concrete nouns contained in the text corpus with accuracies significantly greater than chance.

The findings are being published in the May 30 issue of the journal Science.

“We believe we have identified a number of the basic building blocks that the brain uses to represent meaning,” said Mitchell, who heads the School of Computer Science’s Machine Learning Department. “Coupled with computational methods that capture the meaning of a word by how it is used in text files, these building blocks can be assembled to predict neural activation patterns for any concrete noun. And we have found that these predictions are quite accurate for words where fMRI data is available to test them.”

Just, a professor of psychology who directs the Center for Cognitive Brain Imaging, said the computational model provides insight into the nature of human thought. “We are fundamentally perceivers and actors,” he said. “So the brain represents the meaning of a concrete noun in areas of the brain associated with how people sense it or manipulate it. The meaning of an apple, for instance, is represented in brain areas responsible for tasting, for smelling, for chewing. An apple is what you do with it. Our work is a small but important step in breaking the brain’s code.”

In addition to representations in these sensory-motor areas of the brain, the Carnegie Mellon researchers found significant activation in other areas, including frontal areas associated with planning functions and long-term memory. When someone thinks of an apple, for instance, this might trigger memories of the last time the person ate an apple, or initiate thoughts about how to obtain an apple.

“This suggests a theory of meaning based on brain function,” Just added.

In the study, nine subjects underwent fMRI scans while concentrating on 60 stimulus nouns — five words in each of 12 semantic categories including animals, body parts, buildings, clothing, insects, vehicles and vegetables.

To construct their computational model, the researchers used machine learning techniques to analyze the nouns in a trillion-word text corpus that reflects typical English word usage. For each noun, they calculated how frequently it co-occurs in the text with each of 25 verbs associated with sensory-motor functions, including see, hear, listen, taste, smell, eat, push, drive and lift. Computational linguists routinely do this statistical analysis as a means of characterizing the use of words.

These 25 verbs appear to be basic building blocks the brain uses for representing meaning, Mitchell said.

By using this statistical information to analyze the fMRI activation patterns gathered for each of the 60 stimulus nouns, they were able to determine how each co-occurrence with one of the 25 verbs affected the activation of each voxel, or 3-D volume element, within the fMRI brain scans.

To predict the fMRI activation pattern for any concrete noun within the text corpus, the computational model determines the noun’s co-occurrences within the text with the 25 verbs and builds an activation map based on how those co-occurrences affect each voxel.

In tests, a separate computational model was trained for each of the nine research subjects using 58 of the 60 stimulus nouns and their associated activation patterns. The model was then used to predict the activation patterns for the remaining two nouns. For the nine participants, the model had a mean accuracy of 77 percent in matching the predicted activation patterns to the ones observed in the participants’ brains.

The model proved capable of predicting activation patterns even in semantic areas for which it was untrained. In tests, the model was retrained with words from all but two of the 12 semantic categories from which the 60 words were drawn, and then tested with stimulus nouns from the omitted categories. If the categories of vehicles and vegetables were omitted, for instance, the model would be tested with words such as airplane and celery. In these cases, the mean accuracy of the model’s prediction dropped to 70 percent, but was still well above chance (50 percent).

Plans for future work include studying the activation patterns for adjective-noun combinations, prepositional phrases and simple sentences. The team also plans to study how the brain represents abstract nouns and concepts.

Science, 2008; 320 (5880): 1191 DOI: 10.1126/science.1152876

Predicting Human Brain Activity Associated with the Meanings of Nouns.

Tom M. Mitchell, Svetlana V. Shinkareva, Andrew Carlson, Kai-Min Chang, Vicente L. Malave, Robert A. Mason, and Marcel Adam Just.

The question of how the human brain represents conceptual knowledge has been debated in many scientific fields. Brain imaging studies have shown that different spatial patterns of neural activation are associated with thinking about different semantic categories of pictures and words (for example, tools, buildings, and animals). We present a computational model that predicts the functional magnetic resonance imaging (fMRI) neural activation associated with words for which fMRI data are not yet available. This model is trained with a combination of data from a trillion-word text corpus and observed fMRI data associated with viewing several dozen concrete nouns. Once trained, the model predicts fMRI activation for thousands of other concrete nouns in the text corpus, with highly significant accuracies over the 60 nouns for which we currently have fMRI data.

Written by huehueteotl

May 30, 2008 at 7:39 am

Posted in Neuroscience

Mood Is In The Eye Of The Beholder

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The old saying, “beauty is in the eye of the beholder,” has been scientifically show to be true. A study in a recent issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS), found that variations in eyebrow shape, eyelid position, and wrinkles significantly impact how your facial expressions, and subsequent mood, are perceived by others.

“A key complaint of those seeking facial plastic surgery is that people always tell them they look tired, even though they do not feel tired,” said John Persing, MD, ASPS member and study co-author. “We found that variations in eyebrow contour, drooping of the upper eyelid, and wrinkles may be conveying facial expressions that don’t necessarily match how patients are feeling.”

In the study, a standardized photo of a youthful face was digitally altered to change a number of variables, including eyebrow shape and position; upper and lower eyelid position; upper eyelid drooping and removal of excess skin; and facial wrinkles. Twenty health care workers were given 16 photos and asked to rate, on a scale of 0 to 5, the presence of seven expressions or emotions: tiredness, happiness, surprise, anger, sadness, disgust, and fear. The results for each altered photo were compared with scores from the original unaltered photo. Overall, eyebrow shape had a greater influence than absolute position on perceived mood.

Tiredness

Drooping of the upper eyelid was the biggest indicator of tiredness, according to the study. Simulating skin removal of the upper eyelid, as performed in some eyelid procedures, but not correcting accompanying eyelid ptosis (drooping), resulted in an increase in the perception of tiredness (and sadness). Photos that included an overall elevation of the eyebrows or an increase in the distance between the eyebrow and upper eyelid also increased the perception of tiredness.

Anger & Disgust

Lowering or slanting the inner corner of the eyebrows towards the nose, as well as adding forehead winkles significantly increased the perceived facial expressions of anger and disgust.

Fear & Surprise

Raising the upper eyelids produced an increase in the perception of surprise and fear. Also, raising the outer corner of the eyebrows produced an increase in the perception of surprise.

Sadness

Raising the inner corner of the eyebrows away from the nose was perceived as a sad facial expression.

Happiness

Happiness was perceived by raising the lower eyelid and the presence of crow’s feet, which, according to the study, seem to simulate the cheek elevation that occurs with smiling.

“The eyes and their related structures nonverbally communicate a wide range of expressions that are universal to all people,” said Dr. Persing. “Therefore facial expression should be a factor in how patients and their plastic surgeons select various rejuvenation procedures. As our findings show, even the slightest modification can elicit profound changes in how others perceive us.”

Plastic & Reconstructive Surgery. 121(5):1793-1802, May 2008.

The Influence of Forehead, Brow, and Periorbital Aesthetics on Perceived Expression in the Youthful Face.

Knoll, Bianca I. M.D.; Attkiss, Keith J. M.D.; Persing, John A. M.D.

Abstract:
Background: The purpose of this study was to characterize the relative influence of eyebrow position and shape, lid position, and facial rhytides on perceived facial expression as related to blepharoplasty, with a specific focus on the perception of tiredness.

Methods: A standardized photograph of a youthful upper face was modified using digital imaging software to independently alter a number of variables: brow position/shape, upper/lower lid position, pretarsal show, and rhytides. Subjects (n = 20) were presented with 16 images and asked to quantify, on a scale from 0 to 5, the presence of each of seven expressions/emotions as follows: “surprise,” “anger,” “sadness,” “disgust,” “fear,” “happiness,” and “tiredness.”

Results: Statistically significant values for tiredness were achieved by changes of increasing and decreasing the pretarsal skin crease, lowering the upper eyelid, and depressing the lateral brow. Happiness was perceived by elevation of the lower lid or the presence of crow’s feet. Brow shape had a greater influence than absolute position on perceived expression. Elevation of the lateral brow was perceived as surprise, whereas depression of the medial brow and rhytides at the glabella were perceived as anger and disgust. Elevation of the medial brow elicited a minimal increase for sadness.

Conclusions: This study showed that the perception of tiredness is most affected by the length of pretarsal lid height (e.g., ptosis). Surprisingly, simulating the skin resection of an upper blepharoplasty results in a paradoxical increase in the perception of tiredness as well. Modifications of brow contour elicit profound changes in perceived facial mood to a greater degree than absolute brow position.

(C)2008American Society of Plastic Surgeons

Written by huehueteotl

May 29, 2008 at 7:44 am

Posted in Psychology

Why Are Some People Unable To Express Their Emotions?

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Italian investigators have published a new study on the neurobiologic correlates of the inability to express emotions (alexithymia).

A deficit in interhemispheric transfer was hypothesized in alexithymia more than 30 years ago, following the observation that split-brain patients manifest certain alexithymic characteristics. However, direct evidence of interhemispheric transfer deficit has never been provided. This study investigated the hypothesis of a transcallosal interhemispheric transfer deficit in alexithymia by means of paired-pulse transcranial magnetic stimulation.

A random sample of 300 students was screened for alexithymia using the Italian version of the 20-item Toronto Alexithymia Scale. Eight right-handed males and eight females with high alexithymic scores and an age- and gender-matched group with low alexithymic scores were selected. A first (conditioning) magnetic stimulus was delivered to one motor cortex followed by a second (test) stimulus to the opposite hemisphere at different interstimulus intervals for both motor cortices. Motor evoked responses were recorded from the abductor digit minimi muscles.

At the end of the investigation, high alexithymic subjects showed reduced transcallosal inhibition as compared to low alexithymic subjects at interstimulus intervals of 10, 12 and 14 ms in the left-to-right and right-to-left interhemispheric transfer directions.

Results point to functional differences in transcallosal interactions in high alexithymic as compared to low alexithymic subjects, supporting the hypothesis of an interhemispheric transfer deficit in alexithymia.

Psychother Psychosom. 2008;77(3):175-81. Epub 2008 Mar 10.

Interhemispheric transfer deficit in alexithymia: a transcranial magnetic stimulation study.

Romei V, De Gennaro L, Fratello F, Curcio G, Ferrara M, Pascual-Leone A, Bertini M.

Department of Psychology, University of Rome La Sapienza, Rome, Italy. Vincenzo.Romei@medecine.unige.ch

BACKGROUND: A deficit in interhemispheric transfer was hypothesized in alexithymia more than 30 years ago, following the observation that split-brain patients manifest certain alexithymic characteristics. However, direct evidence of interhemispheric transfer deficit has never been provided. This study investigated the hypothesis of a transcallosal interhemispheric transfer deficit in alexithymia by means of paired-pulse transcranial magnetic stimulation. METHODS: A random sample of 300 students was screened for alexithymia using the Italian version of the 20-item Toronto Alexithymia Scale. Eight right-handed males and eight females with high alexithymic scores and an age- and gender-matched group with low alexithymic scores were selected. A first (conditioning) magnetic stimulus was delivered to one motor cortex followed by a second (test) stimulus to the opposite hemisphere at different interstimulus intervals for both motor cortices. Motor evoked responses were recorded from the abductor digit minimi muscles. RESULTS: High alexithymic subjects showed reduced transcallosal inhibition as compared to low alexithymic subjects at interstimulus intervals of 10, 12 and 14 ms in the left-to-right and right-to-left interhemispheric transfer directions. CONCLUSIONS: Results point to functional differences in transcallosal interactions in high alexithymic as compared to low alexithymic subjects, supporting the hypothesis of an interhemispheric transfer deficit in alexithymia. Copyright (c) 2008 S. Karger AG, Basel.

Written by huehueteotl

May 27, 2008 at 7:42 am

Posted in Neuroscience

Innate Defense Against HIV That Could Lead To New Treatments

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By identifying a protein that restricts the release of HIV-1 virus from human cells, scientists believe they may be closer to identifying new approaches to treatment. The research is published in the advance online edition of Nature Medicine.

https://i2.wp.com/www.iayork.com/Images/2008/1-14-07/HIV_on_macrophage.png

Scientists have known that most human cells contain a factor that regulates the release of virus particles, but until now they have been uncertain about the factor’s identity. Now a research team from Emory University School of Medicine, Vanderbilt University School of Medicine, and Mayo Medical School has identified CAML (calcium-modulating cyclophilin ligand) as the cellular protein that inhibits the release of HIV particles.

CAML works by inhibiting a very late step in the virus lifecycle, leading to the retention of HIV particles on the membrane of the cell. The virus has developed a means of counteracting CAML, through the action of the viral Vpu protein. When Vpu is absent, HIV particles don’t detach from the plasma membrane and instead accumulate by a protein tether at the cell surface.

When the research team depleted CAML in human cells in the laboratory, they found that Vpu was no longer required for the efficient exit of HIV-1 particles from the cell. When they expressed CAML in cell types that normally allow particles to exit freely, the particles remained attached to the cell surface.

“This research is important because it identifies CAML as an innate defense mechanism against HIV,” says senior author Paul Spearman, professor of pediatrics (infectious diseases) at Emory University School of Medicine. “We are continuing to work on the mechanism that Vpu uses to counteract CAML and on defining exactly how CAML leads to virus particle retention on the infected cell membrane. We hope this will lead us to new treatments.”

Nature Medicine

Identification of calcium-modulating cyclophilin ligand as a human host restriction to HIV-1 release overcome by Vpu

Vasundhara Varthakavi, Ellen Heimann-Nichols, Rita M Smith, Yuehui Sun, Richard J Bram, Showkat Ali, Jeremy Rose, Lingmei Ding & Paul Spearman

Published online: 25 May 2008; | doi:10.1038/nm1778

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May 26, 2008 at 2:27 pm

Posted in HIV

When Your Memories Can No Longer Be Trusted

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You went to a wedding yesterday. The service was beautiful, the food and drink flowed and there was dancing all night. But people tell you that you are in hospital, that you have been in hospital for weeks, and that you didn’t go to a wedding yesterday at all. The experience of false memories like this following neurological damage is known as confabulation.

The reasons why patients experience false memories such as these has largely remained a mystery. Studies in amnesic patients have associated confabulation with damage to the orbital and ventromedial prefrontal cortices. However, neuroimaging studies have associated memory-control processes which are assumed to underlie confabulation with the right lateral prefrontal cortex.

A new study by Dr Martha Turner and colleagues at University College London offers some clues as to what might be going on. They used a confabulation battery to investigate the occurrence and localisation of confabulation in an unselected series of 38 patients with focal frontal lesions.

Twelve patients with posterior lesions and 50 healthy controls were included for comparison. Significantly higher levels of confabulation were found in the frontal group, confirming previous reports. More detailed grouping according to lesion location within the frontal lobe revealed that patients with orbital, medial and left lateral damage confabulated in response to questions probing personal episodic memory (PEM).

Patients with orbital, medial and right lateral damage confabulated in response to questions probing orientation to time (OT). Performance-led analysis revealed that all patients who produced a total number of confabulations outside the normal range had a lesion affecting either the orbital region or inferior portion of the anterior cingulate.

These data provide striking evidence that the critical deficit for confabulation has its anatomical location in the inferior medial frontal lobe. Performance on tests of memory and executive functioning showed considerable variability. Although a degree of memory impairment does seem necessary, performance on traditional executive tests is less helpful in explaining confabulation.

Martha S Turner, Lisa Cipolotti, Tarek A Yousry, Tim Shallice
Institute of Cognitive Neuroscience, University College London, London, UK.

Confabulation: Damage to a specific inferior medial prefrontal system.

Cortex. 2008 Jun ;44 (6):637-48 18472034 (P,S,E,B,D)

Confabulation, the pathological production of false memories, occurs following a variety of aetiologies involving the frontal lobes, and is frequently held to be underpinned by combined memory and executive deficits. However, the critical frontal regions and specific cognitive deficits involved are unclear. Studies in amnesic patients have associated confabulation with damage to the orbital and ventromedial prefrontal cortices. However, neuroimaging studies have associated memory-control processes which are assumed to underlie confabulation with the right lateral prefrontal cortex. We used a confabulation battery to investigate the occurrence and localisation of confabulation in an unselected series of 38 patients with focal frontal lesions. Twelve patients with posterior lesions and 50 healthy controls were included for comparison. Significantly higher levels of confabulation were found in the frontal group, confirming previous reports. More detailed grouping according to lesion location within the frontal lobe revealed that patients with orbital, medial and left lateral damage confabulated in response to questions probing personal episodic memory (PEM). Patients with orbital, medial and right lateral damage confabulated in response to questions probing orientation to time (OT). Performance-led analysis revealed that all patients who produced a total number of confabulations outside the normal range had a lesion affecting either the orbital region or inferior portion of the anterior cingulate. These data provide striking evidence that the critical deficit for confabulation has its anatomical location in the inferior medial frontal lobe. Performance on tests of memory and executive functioning showed considerable variability. Although a degree of memory impairment does seem necessary, performance on traditional executive tests is less helpful in explaining confabulation.

Written by huehueteotl

May 22, 2008 at 7:52 am

Posted in Neuroscience

Sleep-deprived Brains Alternate Between Normal Activity And ‘Power Failure’

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Neuroscience researchers at the Duke-NUS Graduate Medical School in Singapore have shown for the first time what happens to the visual perceptions of healthy but sleep-deprived volunteers who fight to stay awake, like people who try to drive through the night.

The scientists found that even after sleep deprivation, people had periods of near-normal brain function in which they could finish tasks quickly. However, this normalcy mixed with periods of slow response and severe drops in visual processing and attention, according to their paper, published in the Journal of Neuroscience on May 21.

“Interestingly, the team found that a sleep-deprived brain can normally process simple visuals, like flashing checkerboards. But the ‘higher visual areas’ — those that are responsible for making sense of what we see — didn’t function well,” said Dr. Michael Chee, lead author and professor at the Neurobehavioral Disorders Program at Duke-NUS. “Herein lies the peril of sleep deprivation.”

The research team, including colleagues at the University of Michigan and University of Pennsylvania, used magnetic resonance imaging to measure blood flow in the brain during speedy normal responses and slow “lapse” responses. The study was funded by grants from the DSO National Laboratories in Singapore, the National Institutes of Health, the National Institute on Drug Abuse, the NASA Commercialization Center, and the Air Force Office of Scientific Research.

Study subjects were asked to identify letters flashing briefly in front of them. They saw either a large H or S, and each was made up of smaller Hs or Ss. Sometimes the large letter matched the smaller letters; sometimes they didn’t. Scientists asked the volunteers to identify either the smaller or the larger letters by pushing one of two buttons.

During slow responses, sleep-deprived volunteers had dramatic decreases in their higher visual cortex activity. At the same time, as expected, their frontal and parietal ‘control regions’ were less able to make their usual corrections.

Scientists also could see brief failures in the control regions during the rare lapses that volunteers had after a normal night’s sleep. However, the failures in visual processing were specific only to lapses that occurred during sleep deprivation.

The scientists theorize that this sputtering along of cognition during sleep deprivation shows the competing effects of trying to stay awake while the brain is shutting things down for sleep. The brain ordinarily becomes less responsive to sensory stimuli during sleep, Chee said.

This study has implications for a whole range of people who have to struggle through night work, from truckers to on-call doctors. “The periods of apparently normal functioning could give a false sense of competency and security when in fact, the brain’s inconsistency could have dire consequences,” Chee said.

“The study task appeared simple, but as we showed in previous work, you can’t effectively memorize or process what you see if your brain isn’t capturing that information,” Chee said. “The next step in our work is to see what we might do to improve things, besides just offering coffee, now that we have a better idea where the weak links in the system are.”

Michael W. L. Chee, Jiat Chow Tan, Hui Zheng, Sarayu Parimal, Daniel H. Weissman, Vitali Zagorodnov, and David F. Dinges
Lapsing during Sleep Deprivation Is Associated with Distributed Changes in Brain Activation
J. Neurosci. 2008 28: 5519-5528; doi:10.1523/JNEUROSCI.0733-08.2008

Lapses of attention manifest as delayed behavioral responses to salient stimuli. Although they can occur even after a normal night’s sleep, they are longer in duration and more frequent after sleep deprivation (SD). To identify changes in task-associated brain activation associated with lapses during SD, we performed functional magnetic resonance imaging during a visual, selective attention task and analyzed the correct responses in a trial-by-trial manner modeling the effects of response time. Separately, we compared the fastest 10% and slowest 10% of correct responses in each state. Both analyses concurred in finding that SD-related lapses differ from lapses of equivalent duration after a normal night’s sleep by (1) reduced ability of frontal and parietal control regions to raise activation in response to lapses, (2) dramatically reduced visual sensory cortex activation, and (3) reduced thalamic activation during lapses that contrasted with elevated thalamic activation during nonlapse periods. Despite these differences, the fastest responses after normal sleep and after SD elicited comparable frontoparietal activation, suggesting that performing a task while sleep deprived involves periods of apparently normal neural activation interleaved with periods of depressed cognitive control, visual perceptual functions, and arousal. These findings reveal for the first time some of the neural consequences of the interaction between efforts to maintain wakefulness and processes that initiate involuntary sleep in sleep-deprived persons.

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May 22, 2008 at 7:48 am

Opium For The People: Burning Incense Is Psychoactive

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Religious leaders have contended for millennia that burning incense is good for the soul. Now, biologists have learned that it is good for our brains too. An international team of scientists, including researchers from Johns Hopkins University and the Hebrew University in Jerusalem, describe how burning frankincense (resin from the Boswellia plant) activates poorly understood ion channels in the brain to alleviate anxiety or depression. This suggests that an entirely new class of depression and anxiety drugs might be right under our noses.

“In spite of information stemming from ancient texts, constituents of Bosweilla had not been investigated for psychoactivity,” said Raphael Mechoulam, one of the research study’s co-authors. “We found that incensole acetate, a Boswellia resin constituent, when tested in mice lowers anxiety and causes antidepressive-like behavior. Apparently, most present day worshipers assume that incense burning has only a symbolic meaning.”

To determine incense’s psychoactive effects, the researchers administered incensole acetate to mice. They found that the compound significantly affected areas in brain areas known to be involved in emotions as well as in nerve circuits that are affected by current anxiety and depression drugs. Specifically, incensole acetate activated a protein called TRPV3, which is present in mammalian brains and also known to play a role in the perception of warmth of the skin. When mice bred without this protein were exposed to incensole acetate, the compound had no effect on their brains.

“Perhaps Marx wasn’t too wrong when he called religion the opium of the people: morphine comes from poppies, cannabinoids from marijuana, and LSD from mushrooms; each of these has been used in one or another religious ceremony.” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “Studies of how those psychoactive drugs work have helped us understand modern neurobiology. The discovery of how incensole acetate, purified from frankincense, works on specific targets in the brain should also help us understand diseases of the nervous system. This study also provides a biological explanation for millennia-old spiritual practices that have persisted across time, distance, culture, language, and religion–burning incense really does make you feel warm and tingly all over!”

Arieh Moussaieff, Neta Rimmerman, Tatiana Bregman, Alex Straiker, Christian C. Felder, Shai Shoham, Yoel Kashman, Susan M. Huang, Hyosang Lee, Esther Shohami, Ken Mackie, Michael J. Caterina, J. Michael Walker, Ester Fride, and Raphael Mechoulam

Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain.

The FASEB Journal. Published online before print May 20, 2008 as doi: 10.1096/fj.07-101865

Burning of Boswellia resin as incense has been part of religious and cultural ceremonies for millennia and is believed to contribute to the spiritual exaltation associated with such events. Transient receptor potential vanilloid (TRPV) 3 is an ion channel implicated in the perception of warmth in the skin. TRPV3 mRNA has also been found in neurons throughout the brain; however, the role of TRPV3 channels there remains unknown. Here we show that incensole acetate (IA), a Boswellia resin constituent, is a potent TRPV3 agonist that causes anxiolytic-like and antidepressive-like behavioral effects in wild-type (WT) mice with concomitant changes in c-Fos activation in the brain. These behavioral effects were not noted in TRPV3-/- mice, suggesting that they are mediated via TRPV3 channels. IA activated TRPV3 channels stably expressed in HEK293 cells and in keratinocytes from TRPV3+/+ mice. It had no effect on keratinocytes from TRPV3-/- mice and showed modest or no effect on TRPV1, TRPV2, and TRPV4, as well as on 24 other receptors, ion channels, and transport proteins. Our results imply that TRPV3 channels in the brain may play a role in emotional regulation. Furthermore, the biochemical and pharmacological effects of IA may provide a biological basis for deeply rooted cultural and religious traditions.—Moussaieff, A., Rimmerman, N., Bregman, T., Straiker, A., Felder, C. C., Shoham, S., Kashman, Y., Huang, S. M., Lee, H., Shohami, E., Mackie, K., Caterina, M. J., Walker, J. M., Fride, E., Mechoulam, R. Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain.

Written by huehueteotl

May 21, 2008 at 7:36 am

Posted in Neuroscience