Some feel the need to explore more than others. This apparently random characteristic really makes a difference to personalities, a mice experiment shows. Those that like to be adventurous and have the capacity to do so, develop different brains than those who stay mostly in the same place.... Read more »
Freund, J., Brandmaier, A., Lewejohann, L., Kirste, I., Kritzler, M., Kruger, A., Sachser, N., Lindenberger, U., & Kempermann, G. (2013) Emergence of Individuality in Genetically Identical Mice. Science, 340(6133), 756-759. DOI: 10.1126/science.1235294
Defects of mitochondrial function have been identified in several neurodegenerative diseases. These include abnormalities induced by mutations of mitochondrial DNA (mtDNA) those caused by mutation of nuclear genes encoding mitochondrial proteins, and in some cases, exposure to mitochondrial toxins.MtDNA mutation are associated with a variety of progressive encephalomyopathies inn which there is evidence of neurodegeneration. These include Kearns-Sayre syndrome myopathy, encephalopathy, lactic acidosis and stroke – like episodes (MELAS) and Myoclonic epilepsy with ragged red fibers (MERRF) and Leigh’s syndrome. In Leber’s heredity optic neuropathy (LHON), there is degeneration of retinal ganglion cells. Occasional reports have described mtDNA mutation in association with Parkinson’s Diseases (PD) and amyotrophic lateral sclerosis (ALS).Mutation in the nuclear gene for mtDNA polymerase gamma (POLG) have been found in a range of disorders that include Alper’s Syndrome, progressive external opthalmoplegia (PEO), sensory ataxia, neuropathy, dysarthria and ophthalmoplegia (SANDO) and parkinsonism. Although most cases of Parkinsonism due to POLG mutations have been preceded by PEO, some have been described with only Parkinsonism and neuropathy. The early onset from hepatocerebral mtDNA depletion is associated with mutation in the deoxyguanosine kinase gene and thymidine phosphorylase mutation are a cause of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Mutation have been identified in nuclear genes for mitochondrial protein involved in the assembly and maintenance of cytochrome oxidase including SCO2, SURF1, COX10, COX15 and LRPPRC. These results in autosomal recessive COX deficiency that usually presents in early life with Leigh syndrome, myopathy and encephalopathy, lactic acidosis and a progressive course with early death.There is deficiency in complex I activity in PD substantia nigra and platelets. Complex I is the target of toxin known to produce parkinsonian features in human e.g. MPTP and anonnacin, and animal model of PD e.g. rotenone and tetrahydroisoquinoline. The pathogenesis of PD also includes protein aggregation (Lewy bodies). Mitochondrial dysfunction will contribute to dysfunction of the energy dependent ubiquitin proteasomal system (UPS) and oxidative stress will add to the substrate load. Several of the single gene mutation causing familial PD has been identified as mitochondrial proteins including PINK1, DJ1 and parkin. The cellular disruption of the latter appears to depend upon the stage of cell differentiation. A proportion of LRRK2 is associated with the outer mitochondrial membrane. Mitochondrial dysfunction has also been identifies in AD, ALS and Huntington’s diseases although the relationship to pathogenesis in the respective diseases remain unknown. McFarland R, Taylor RW, & Turnbull DM (2010). A neurological perspective on mitochondrial disease. Lancet neurology, 9 (8), 829-40 PMID: 20650404Venna N (2004). Mitochondrial neurological diseases: a clinician's perspective. Neurology India, 52 (3), 305-6 PMID: 15472416... Read more »
McFarland R, Taylor RW, & Turnbull DM. (2010) A neurological perspective on mitochondrial disease. Lancet neurology, 9(8), 829-40. PMID: 20650404
Venna N. (2004) Mitochondrial neurological diseases: a clinician's perspective. Neurology India, 52(3), 305-6. PMID: 15472416
(source)Hi Julie, WOW!Dogs in clothes. Corgis in bikinis at the beach. Greyhounds in onesies. We people do some weird things to our canine friends, no?! I'm pretty sure I wouldn't enjoy being dressed up in a padded outfit all day long, so I think I'll pass on sharing that experience with my dogs. As you said, cultural perceptions, ethics and expectations add a whole layer of extra consideration. It's not always easy to work out what dogs want or need. That's why I like science. It helps us work this stuff out.I've been super busy this week - working hard (as always!) and still thinking a lot about dogs living in kennel facilities. So I wanted to pull your head away from dogs dressed as flowers, back to dogs getting the opportunity to smell the flowers. No, really. Lavender in fact.(source)Dogs should stop to smell the flowers. Especially lavender.When I talk to people about the body of research that's been conducted in the area of environmental enrichment for dogs housed in kennels, they never fail to be amazed at what has been studied. Or what hasn't. One topic that usually results in a snort, a laugh or a quizzical raised eyebrow is olfactory (smelly) stimulation. Which is kind of weird. Because we know that dogs can smell on a level that's basically in another galaxy compared to our smelling experiences. Research conducted in a rescue shelter kennel in 2005 exposed dogs to five different diffused aromas: - a blank control, or essential oil of- chamomile - lavender - peppermint- rosemary The study showed that olfactory stimulation had a significant effect on behaviour. Dogs were more likely to rest and less likely to bark when exposed to the smells of lavender and chamomile. Peppermint and rosemary exposure resulted in more active and noisy behaviour. The researchers suggested that the welfare of dogs in shelter kennel environments (and also their attractiveness to potential adopters) could be improved by using this kind of aromatherapy. What a dog's nose knows.Further research has shown a similar effect of lavender in effecting the behaviour of dogs with travel-induced excitement in cars: they spent more time sitting, resting and less time vocalising when they were exposed to the smell of lavender.Interestingly, human studies show a similar effect of lavender on us: reduced mental stress.So if a dog is in a kennel environment and can't get out to romp in a field of flowers, or chomp them up (as dogs tend to do!), perhaps we can help them out by giving them something... Read more »
Wells Deborah L. (2009) Sensory stimulation as environmental enrichment for captive animals: A review. Applied Animal Behaviour Science, 118(1-2), 1-11. DOI: 10.1016/j.applanim.2009.01.002
Graham Lynne, Wells Deborah L., & Hepper Peter G. (2005) The influence of olfactory stimulation on the behaviour of dogs housed in a rescue shelter. Applied Animal Behaviour Science, 91(1-2), 143-153. DOI: 10.1016/j.applanim.2004.08.024
Wells Deborah L. (2006) Aromatherapy for travel-induced excitement in dogs. Journal of the American Veterinary Medical Association, 229(6), 964-967. DOI: 10.2460/javma.229.6.964
The range of tools used to study the brain is vast. Neuroscientists toss together ideas from genetics, biochemistry, immunology, physics, computer science, medicine and countless other fields when choosing their techniques. We work on animals ranging from barely-visible worms and the common fruit fly to complicated creatures like mice, monkeys, and men. We record from […]... Read more »
Marder, E. (2011) Colloquium Paper: Variability, compensation, and modulation in neurons and circuits. Proceedings of the National Academy of Sciences, 108(Supplement_3), 15542-15548. DOI: 10.1073/pnas.1010674108
Prefrontal Cortex Highlighted in RedIdentifying valid biomarkers for psychosis and schizophrenia is an active focus in brain research.Tyronne Cannon, Ph.D. from Yale University recently presented a summary of research on this topic at the William K. Warren Neuroscience Symposium in Tulsa, Oklahoma. Here are my notes from his presentation along with related free full-text research references.Biomarker research in psychosis is important because current treatment for psychosis with the antipsychotic drugs is limited by:discovery by serendipity without a specific molecular mechanismabsence of effect on psychosis negative symptoms (anergia, anhedonia and amotivation)poor tolerability of antipsychotic drugs with significant compliance issuesno evidence that antipsychotic drugs modify the progression of the diseaseBiomarker research in psychosis is promising because an extended prodrome period is present in childhood and adolescence. Biomarker research can be divided into markers with a progressively deviant pattern and those with a stable deviant pattern.Two studies are available to summarize current findings: The North American Prodrome Longitudinal Study, parts I and II (NAPLS I and NAPLS II). These studies have identified three biomarker candidate categories:Hormonal disruption involving the hypothalamic-pituitary-adrenal (HPA) axisEvent related potential abnormalities including the p300 marker and an NMDA synapse-related marker identified in a negativity mismatch taskBrain magnetic resonance imaging (MRI) showing a greater cortical gray matter volume decline (primarily in bilateral frontal cortex regions) in high-risk individuals who later convert to psychosisThe first two biomarkers appear to be of the stable deviant type while the gray matter deficit biomarker appears to be a progressive deviant markerAn important potential confounding issue in gray matter deficits is the role of antipsychotic drug exposure in producing gray matter changes. Research to date supports an independent contribution of psychosis progression risk with frontal gray matter reductionProgress in understanding the MRI biomarker changes in psychosis/schizophrenia require a better understanding of the mechanism of this change. At least three avenues of research for a mechanism are promising:Disruption of neuroplasticity: fetal hypoxia environments produce impairment in brain neuroplasticity possibly through disruption of the BDNF systemDisruption of brain inflammation: risk for progression to psychosis is linked to increase blood inflammation using a multiplex composite variable. This variable is associated with 35% of the variance in brain gray matter volumesHPA-Glutamate pathways: The glutamate pathway is known to be involved in psychosis with the psychotic effect produce by PCP and ketamine. It is possible glutamate disruption effects gray matter reduction through effects on the microgliaAlthough not discussed in this lecture, other promising targets for understanding psychosis mechanism and risk include: neuropsychologic deficits, brain white matter abnormalities and fMRI activation abnormalities and resting connectivity deficits.Further identification of biomarkers in psychosis will be key in designing prevention strategies and in smart drug development through understanding the mechanism of risk and progression of the disease.Readers with more interest in this topic are directed to the free full-text citations below.Image of the frontal cortex noted to be a biomarker of psychosis risk above is from a iPad screen shot from the Sun D, van Erp TG, Thompson PM, Bearden CE, Daley M, Kushan L, Hardt ME, Nuechterlein KH, Toga AW, & Cannon TD (2009). Elucidating a magnetic resonance imaging-based neuroanatomic biomarker for psychosis: classification analysis using probabilistic brain atlas and machine learning algorithms. Biological psychiatry, 66 (11), 1055-60 PMID: 19729150... Read more »
Sun D, van Erp TG, Thompson PM, Bearden CE, Daley M, Kushan L, Hardt ME, Nuechterlein KH, Toga AW, & Cannon TD. (2009) Elucidating a magnetic resonance imaging-based neuroanatomic biomarker for psychosis: classification analysis using probabilistic brain atlas and machine learning algorithms. Biological psychiatry, 66(11), 1055-60. PMID: 19729150
Seidman LJ, Giuliano AJ, Meyer EC, Addington J, Cadenhead KS, Cannon TD, McGlashan TH, Perkins DO, Tsuang MT, Walker EF.... (2010) Neuropsychology of the prodrome to psychosis in the NAPLS consortium: relationship to family history and conversion to psychosis. Archives of general psychiatry, 67(6), 578-88. PMID: 20530007
Gee DG, Karlsgodt KH, van Erp TG, Bearden CE, Lieberman MD, Belger A, Perkins DO, Olvet DM, Cornblatt BA, Constable T.... (2012) Altered age-related trajectories of amygdala-prefrontal circuitry in adolescents at clinical high risk for psychosis: a preliminary study. Schizophrenia research, 134(1), 1-9. PMID: 22056201
Different brain areas are activated when we choose to suppress an emotion, compared to when we are instructed to inhibit an emotion, according a new study from the UCL Institute of Cognitive Neuroscience and Ghent University. In this study, published in Brain Structure and Function (citation below), the researchers scanned the brains of healthy participants and … Read More →... Read more »
Kühn, S., Haggard, P., & Brass, M. (2013) Differences between endogenous and exogenous emotion inhibition in the human brain. Brain Structure and Function. DOI: 10.1007/s00429-013-0556-0
The world of parasites is full of incredible tales of manipulation and mind-control as these creatures twist their hosts to …Continue reading »... Read more »
Libersat, F., & Gal, R. (2012) What can parasitoid wasps teach us about decision-making in insects?. Journal of Experimental Biology, 216(1), 47-55. DOI: 10.1242/jeb.073999
Herzner, G., Schlecht, A., Dollhofer, V., Parzefall, C., Harrar, K., Kreuzer, A., Pilsl, L., & Ruther, J. (2013) Larvae of the parasitoid wasp Ampulex compressa sanitize their host, the American cockroach, with a blend of antimicrobials. Proceedings of the National Academy of Sciences, 110(4), 1369-1374. DOI: 10.1073/pnas.1213384110
If Valium makes you groggy, and Ambien makes you sleepwalk…
A compound that blocks a brain receptor you probably have never heard of may hold the key to the next generation of sleeping pills—and there is always a next generation of sleeping pills.
A new class of hypnotic compounds that serve as antagonists for the neurotransmitter orexin may combat insomnia without the “confusional arousals” that have come to plague some users of zolpidem, otherwise known as Ambien. Sleepwalking, sleep driving, and sleep sex are common among the reports. Orexin is involved in central nervous system arousal. So-called DORAs, or dual orexin receptor antagonists, discovered in 1998, are being seen as potential therapies for insomnia, without the daytime drowsiness and rebound insomnia typical of existing treatments. The sleep disorder narcolepsy, which is in many ways the exact opposite of insomnia, is caused by “an autoimmune attack against neurons that express orexin,” according to Emmanuel Mignot of Stanford’s Center for Sleep Sciences, in an article for Science magazine.
If these drugs are already being thought of as potential insomnia therapies, their addiction potential will have to be much lower than that of earlier generations of sleep medications. But that just might be the case, since DORA-style drugs don’t appear to promote sleep by inhibiting brain activity through neurotransmitter systems for GABA, as most existing treatments do. A study last month in Science Translational Medicine by J.M. Uslaner and coworkers asserted that DORA-type drugs caused less cognition and memory impairment in rats than Valium or Ambien, and are effective at lower doses. With drugs that modulate the orexin system, the hope is that there would be less rebound insomnia, less memory loss, less addiction, and less weird wandering around like a zombie in the middle of the night.
The search for safer sleep drugs was recently given a shot in the arm by a disturbing report from the U.S. Substance Abuse & Mental Health Services Administration (SAMHSA). Emergency room visits caused by Ambien more than doubled from 2005 to 2010, and patients 45 years and up accounted for 74% of adverse zolpidem reactions. Overall, male ER visits went up by 144%, whereas female ER visits went up almost twice as much. Overall, women made up two-thirds of all Ambien-related emergency visits—a bald fact that led the Food & Drug Administration (FDA) in January 2013 to cut the recommended dose for females in half. Lower doses were also recommended for men as well.
But a closer look at the report shows the typical confusion of polydrug use: 50% of emergency department visits for Ambien involved its use in combination with other drugs. And in 37% of cases, Ambien was used specifically in combination with other central nervous system depressants. “Although short-term medications can help patients,” SAMSHA Administrator Pamela Hyde said in a prepared statement, “it is exceedingly important that they be carefully used and monitored.”
A new class of medications based on orexin-active drugs would follow three earlier generations of sleeping pills. And each new generation of sleeping pills seems to bring its own history of unintended consequences.
In the beginning, there was meprobamate, the postwar tranquilizer known as Miltown. In additional, powerful barbiturates like phenobarbital were marketed as miracle drugs for the anxious insomniac. By the 1950s, it had become clear that these drugs were seriously addictive, and dangerous in overdose. Emmanuel Mignot noted that in high doses, barbiturates “lead to pulmonary arrest and death, outcomes that gained further notoriety with the deaths of celebrities Marilyn Monroe and Jimi Hendrix.” Barbiturates do their work by activating chloride channel receptors for the inhibitory neurotransmitter GABA. In addition, strong sedatives were increasingly being used on psychotic patients in the 1950s, and found their way into the treatment of insomnia.
The continued promise of a safe and effective hypnotic for insomnia drove research that led to the development of the first benzodiazepines, and eventually to Valium. The benzodiazepines like Valium were safer in overdose, came in a bewildering variety of flavors, and found widespread use for sleep induction—but also as anticonvulsants, anti-anxiety agents, and muscle relaxers. The benzos bound to GABA receptor sites just like the barbiturates, but the effects were less extensive. Still, it was not long before Valium, another “perfect” drug, showed it’s adverse side, in the form of sedation, memory problems, and addiction.
Then, in 2007 came the 3rd generation, in the form of the now wildly popular “Z-drugs”—zolpidem, (Ambien) zopiclone (used overseas), and zaleplon (Sonata). And again, the side effect profiles looked better in testing, the effective dose was lower, and the binding site—GABA again—looked like the right place to bring on slower brain activity and more inclination toward sleep without the “knockout effect” of earlier barbiturates and benzos. These drugs are now the default treatment for insomnia. But over time, predictably, problems revealed themselves: “Occasional problems with dependence, tolerance, and ‘confusional arousals’ are still reported with Z-drugs…. And viewed with some suspicion by doctors and patients,” writes Mignot.
Put simply, any sleep treatment that relies on the broad-brush inhibition of GABA will likely produce a range of unwelcome side effects. There are only about 70,000 orexin-producing neurons in the hypothalamus, researchers have found. But this small band of neurons has projections to histamine systems, as well as “the adrenergic locus coeruleus, and various cholinergic and aminergic cell groups,” as Mignot sums up the research. “Blocking orexin may thus be closer to treating the underlying issue of excess alertness in insomnia compared to promoting sleep by inhibiting brain activity.”
That’s the idea, at least. And it may represent a change in thinking. Researchers are no longer looking for a better knockout drug by bludgeoning the brain into inactivity. Instead, they are looking for ways to combat hyper-alertness as a key component of insomnia.
Uslaner J.M., Tye S.J., Eddins D.M., Wang X., Fox S.V., Savitz A.T., Binns J., Cannon C.E., Garson S.L. & Yao L. & (2013). Orexin Receptor Antagonists Differ from Standard Sleep Drugs by Promoting Sleep at Doses That Do Not Disrupt Cognition, Science Translational Medicine, 5 (179) 179ra44-179ra44. DOI: 10.1126/scitranslmed.3005213
Photo Credit: F Delventhal under license from Creative Commons.
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Uslaner J. M., Tye S. J., Eddins D. M., Wang X., Fox S. V., Savitz A. T., Binns J., Cannon C. E., Garson S. L., & Yao L. (2013) Orexin Receptor Antagonists Differ from Standard Sleep Drugs by Promoting Sleep at Doses That Do Not Disrupt Cognition. Science Translational Medicine, 5(179), 179-179. DOI: 10.1126/scitranslmed.3005213
A particularly sinister aspect of drug addiction is relapse. To the ex-addict, environmental cues, life stressors and even the drug itself serve as the sirens’ call, beckoning them back into the deadly realm of abuse. Currently, doctors battle heroin temptations with psychotherapy and replacement opioid drugs, such as methadone. While effective, these treatments rely heavily [...]... Read more »
Schlosburg, J., Vendruscolo, L., Bremer, P., Lockner, J., Wade, C., Nunes, A., Stowe, G., Edwards, S., Janda, K., & Koob, G. (2013) Dynamic vaccine blocks relapse to compulsive intake of heroin. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1219159110
photo: jagaro.netLack of awareness of illness, poor insight or ‘denial’ are regarded as fundamental problems in neurology and psychiatry. The ‘object’ of the awareness differs in different conditions. For example a stroke patient may deny their hemiplegia (anosognosia) – a deficit which is visible and objective; a person with Alzheimer’s disease may be unaware of memory problems – which though measurable, are not readily apparent to the observer. Finally, a schizophrenic patient with hallucinations may or may not accept that the ‘voices’ that they alone hear are part of a mental illness. In neuropsychiatry the discrepancy between the patients’ and the relatives’ ratings provide a useful measure of ‘insight’. In psychiatry, it is more common to use a clinician rating and to consider separate domains. It has been have suggested that insight in psychosis concerns 3 domains: (1) awareness of mental disorder, (2) ability to re-label psychotic phenomena as pathological, (3) compliance with treatment. This last dimension is obviously important clinically. One question for research is whether these different types of lack of awareness share a common aetiology. Within schizophrenia, insight appears to be correlated with general intellectual functioning. However, this does not explain why many patients are able to detect signs of mental disorder in another person but not themselves. There is some evidence that additional executive or ‘frontal lobe’ deficits contribute to lack of insight. More recently neuroimaging studies using MRI and voxel-based morphometric techniques have shown areas of reduced grey matter density that correlate with loss of various components of insight. Hence insight in psychiatry and neurology has come together thanks to advances in brain imaging.Pijnenborg GH, van Donkersgoed RJ, David AS, & Aleman A (2013). Changes in insight during treatment for psychotic disorders: a meta-analysis. Schizophrenia research, 144 (1-3), 109-17 PMID: 23305612... Read more »
Pijnenborg GH, van Donkersgoed RJ, David AS, & Aleman A. (2013) Changes in insight during treatment for psychotic disorders: a meta-analysis. Schizophrenia research, 144(1-3), 109-17. PMID: 23305612
Scientists have successfully tested the “dynamic” vaccine against heroin in rats that prevents the heroin and its metabolic products in the body from reaching the brain. This vaccine is ready to be tested in human beings.
Proceedings of the National Academy of Sciences (PNAS)
Heroin addiction affects more than 10 million people globally and the development of such vaccine is really a part of success against such addition.
“The effects of the heroin vaccine are more dramatic than any we’ve ever seen and have been tested more rigorously in an animal model,” said George Koob, the study’s senior author.
Kim Janda, senior study author, said that the vaccine produces antibodies and these antibodies move in the bloodstream and deactivate the heroin and the related breakdown products.
“It’s like the old ’80s game Pac-Man,” Janda said. “They immediately seek out the target and sequester it.”
Although the vaccine worked well in rats but still the studies are needed on human beings and the researchers are looking for a drug company or a philanthropist for the funds for the clinical trials.
However, researchers said that after the success of heroin vaccine on human beings, it could become a part of therapy for heroin addiction.
“Our vaccine represents a promising adjunct therapy for heroin addiction, providing continuous heroin antagonism, requiring minimal medical monitoring and patient compliance,” Researchers wrote
The Scripps Research Institute, U-T San Diego
Schlosburg, J., Vendruscolo, L., Bremer, P., Lockner, J., Wade, C., Nunes, A., Stowe, G., Edwards, S., Janda, K., & Koob, G. (2013). Dynamic vaccine blocks relapse to compulsive intake of heroin Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1219159110... Read more »
Schlosburg, J., Vendruscolo, L., Bremer, P., Lockner, J., Wade, C., Nunes, A., Stowe, G., Edwards, S., Janda, K., & Koob, G. (2013) Dynamic vaccine blocks relapse to compulsive intake of heroin. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1219159110
It struck me recently that one of the key differences between economists and neuroscientists studying decision-making is their interest in dynamics. Economists seem more interested in explaining how behavior operates (or should operate) on average whereas neuroscientists would like to explain trial-to-trial variability. Decisions are rarely made just once in a lifetime, but are instead made repeatedly. [...]... Read more »
Hampton, A., Bossaerts, P., & O'Doherty, J. (2008) Neural correlates of mentalizing-related computations during strategic interactions in humans. Proceedings of the National Academy of Sciences, 105(18), 6741-6746. DOI: 10.1073/pnas.0711099105
Zhu, L., Walsh, D., & Hsu, M. (2012) Neuroeconomic Measures of Social Decision-Making Across the Lifespan. Frontiers in Neuroscience. DOI: 10.3389/fnins.2012.00128
Four years ago, neuroscientists became aware of an ominous-sounding manuscript entitled “Voodoo Correlations In Social Neuroscience”. This piece was eventually published under a more prosaic name but it still hit home, with nearly 500 citations so far. To me, this paper marked the start of a new era of ‘critical’ (in the proper sense of [...]... Read more »
Kilner, J. (2013) Bias in a common EEG and MEG statistical analysis and how to avoid it. Clinical Neurophysiology. DOI: 10.1016/j.clinph.2013.03.024
While male birds are singing elaborate arias and flashing their feathers, it's easy to imagine their female counterparts are unimportant actors. Duller and quieter, all a lady bird has to do is hold still and let one of these frantic performers mate with her. Yet in brown-headed cowbirds, at least, the quiet female keeps the whole society in order. Scientists discovered this by targeting a tiny portion of the female brain and frying it.
Males of the species Molothrus ater use their songs to compete with each other and to woo females. Once a a mating pair forms, they stay faithful to each other for the whole mating season, the male guarding his partner from rivals.
Near the top of the bird brain, a region called nucleus HVC controls females' choosiness toward their potential mates. Scientists at the University of Pennsylvania and Wilfrid Laurier University performed brain surgery on female cowbirds, carefully destroying only this region. Then they put their lobotomized females back into the dating arena to see what would happen.
First, the ladies listened to recordings of male songs. The researchers played tunes sung by a variety of males and observed the females' responses. (When they like what they hear, female cowbirds show it by crouching down in a copulation-ready pose.)
Normal females were choosy, only responding to the highest-quality male songs. Females who'd had brain surgery, though, responded positively to every song.
The researchers wanted to see what effect the females' new, lax attitude would have in cowbird society. So they put post-surgery females, normal females, and males in one big group together. Then they watched.
At first, it looked like nothing was different. Females missing their HVC seemed to act the same as females with intact brains; once they were all together in the aviary, there was no clear difference in how often females approached male birds or in how they "chattered" back at males to encourage their singing.
Nevertheless, something had changed. The other birds in the aviary treated post-surgery females differently. For one thing, females missing their HVC were serenaded by a greater variety of males, even once they'd chosen a mate. Normally, a female who's bonded with a male hears his song almost exclusively. This is a measure of how strong the bond between partners is, says study author David White. Now, with more males bending a female's ear, her pair bond was weaker.
There were other changes too. With the altered females introduced into the group, female birds competed more for mates. And the whole hierarchy of male birds, which is established before the breeding season starts, was disrupted. Male cowbirds sing at each other to show who's dominant. After the HVC-less females came to live with them, the rules about which males were dominant singers shifted significantly.
"The result in this paper turned everything around for us," White says.
Previously, it had seemed to be the male cowbird's responsibility to create a strong bond with his partner. Females appeared to be passive agents in the group. "They don't sing, they don't fight," White says. "They don't, to our eye, do much of anything." Yet when the choosiness was erased from females' brains, the whole group dynamic changed. "Now we could see that it was the female that was playing a much more active role in pair-bonding, and in all sorts of other roles within the social network," White says. Everything depended on her song preferences.
Incidentally, it's not clear why female cowbirds bond with males at all.
Females have likely evolved to pick mates whose songs demonstrate—somehow—that they have the best genes. Then the males keep singing to the females throughout the breeding season, strengthening the bond between them.
Usually, White says, bird couples only form strong bonds when both parents will need to care for the young. But cowbirds "are very bad parents overall" who abandon their eggs in the nests of other birds. The powerful bond between cowbird partners "really makes no sense," White says.
Yet once they're bonded, males direct almost all their singing to their partner and never try to mate with other birds. "They follow each other around, they eat together, he comes when she calls him," White says. If a female dies or disappears, he adds, "her pairmate just becomes a wreck. We call it the widowed male phenomenon."
After the loss of his mate, the male gives up for the season. "He flies around looking for her," White says. To him, at least, the quiet female never seemed unimportant.
Maguire, S., Schmidt, M., & White, D. (2013). Social Brains in Context: Lesions Targeted to the Song Control System in Female Cowbirds Affect Their Social Network PLoS ONE, 8 (5) DOI: 10.1371/journal.pone.0063239
Image: female brown-headed cowbird by JanetandPhil (via Flickr)
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Maguire, S., Schmidt, M., & White, D. (2013) Social Brains in Context: Lesions Targeted to the Song Control System in Female Cowbirds Affect Their Social Network. PLoS ONE, 8(5). DOI: 10.1371/journal.pone.0063239
We've been talking about some of the most cutting edge intracellular visualization techniques lately. Array tomography and Serial block-face electron microscopy have been featured. Today we'll talk about STORM imaging. STORM imaging (Xu et al., 2013)STORM stands for Stochastic Optical Reconstruction Microscopy. While Array tomography and Serial block-face EM are both revolutionary in that they can combine very high resolution imaging with relatively large volumes of tissue, STORM is an advancement that lets you see tiny tiny little molecules within the cell. The problem with 'normal' imaging is that molecules are smaller than the diffraction of light. Example of the STORM resolution (from Zhuang lab's webpage)In the figure above, imaging some tiny molecules next to each other is impossible with traditional fluorescence microscopy, but with STORM, you can resolve 10s of nanometers (nm).To do this, STORM uses photoswitchable dyes, which means that the dye can be turned on or off. This allows researchers to turn on tiny little areas and then turn them off. If all the dye is turned on all at once, the image will look like a big mess because the signals will all overlap each other. But turning on only a few at a time allows you to estimate where the actual protein or molecule is."The imaging process consists of many cycles during which fluorophores are activated, imaged, and deactivated. In each cycle only a subset of the fluorescent labels are switched on, such that each of the active fluorophores is optically resolvable from the rest. This allows the position of these fluorophores to be determined with nanometer precision." -Zhuang lab webpage So what amazing things can they do with this STORM?A recent paper by Xu et al. (2013) found that the actin which plays a huge role in the intracellular structure of a neuron, has a specific ring-like structure along the axons.Xu et al., 2013 Figure 4FThis is the kind of research that will immediately go into neuroscience and cell biology textbooks. Xu et al. discovered how actin was structured along the axon simply by being able to 'see it'. Not only did they discover the structure of actin and spectrin (magenta above) in the axon, but they also found some other interesting molecular patterns that appear to relate to the actin ring structure. The sodium channels, which control action potential propagation down the axon, are concentrated about half way between the ends of the spectrin tetramers. The potential for super-resolution microscopy like STORM is huge. The location of molecules with relation to one another probably plays a huge role in the function of cells and now we have the tools to map them.© TheCellularScaleXu K, Zhong G, & Zhuang X (2013). Actin, spectrin, and associated proteins form a periodic cytoskeletal structure in axons. Science (New York, N.Y.), 339 (6118), 452-6 PMID: 23239625... Read more »
Xu K, Zhong G, & Zhuang X. (2013) Actin, spectrin, and associated proteins form a periodic cytoskeletal structure in axons. Science (New York, N.Y.), 339(6118), 452-6. PMID: 23239625
Components of Brain Limbic SystemAdvances in the diagnosis and treatment of brain disorders like bipolar disorder, schizophrenia and autism are a public health priority.Dr. Thomas Insel, director at NIMH recently presented a TED talk that emphasized the need to rethink how we conceptualize and study these types of disorders. He argues for a need to redefine mental disorders as brain disorders. Advances in brain research tools are likely to provide improvements in early diagnosis and early treatment to reduce the morbidity and mortality of these brain disorders.I am posting my notes on Dr. Insel's presentation, as well as the fifteen minute YouTube video of the presentation.Additionally, I have provided links to two free full-text manuscripts on this topic for readers with more interest.MY NOTES on TED presentation Mental Disorders as Brain Disorders: Dr. Thomas InselScience can save lives-evidenced by many startling advances in medicine over the last 20 to 30 yearsChildhood cute lymphoblastic leukemia mortality decreased dramatically (90% to 10%)63% reduction in mortality due to heart diseaseAIDS mortality decliningStroke mortality decreasing due to early intervention programsEarly detection and early intervention are keyHowever, some areas are not improvingOne example of this is suicide--38,000 suicides per year in U.S., one every 15 minutesSuicide rates have not declined over the last 20 to 30 years90% of suicides linked to diagnosable mental disorders, depression, bipolar disorder, schizophreniaDisability is also common in mental disorders30% of all disability can be traced to disorders of the brain or neuropsychiatric disordersDisability in mental disorders due to fact many have early age of onsetMany are chronic disorder beginning in adolescents and young adultsNew terminology needed to change our thinking and research focusThese diseases are not mental disorders or behavioral disorders but brain disordersHuman brain complex 100 billion neurons, 100 trillion synapsesEvidence these are disorders of the human connectome (wiring circuites of the brain)Depression, OCD, PTSD show evidence of connectivity deficitsSchizophrenia: early deficits in brain gray matter volume of brain cortexGray matter pruning excess in schizophrenia crosses the threshold for psychosisBehavior often the last thing to to change in brain disordersNew tools are emerging in brain disordersThese tools promise early detection and early intervention in brain disordersHow soon with this occur? We don't know but the following quote is relevant:"We always overestimate the change that will occur in the next two years and underestimate the change that will occur in the next ten." quote by Bill Gates, Jr.MY COMMENTS: I agree with the need to redefine many disorders previously defined as mental disorders as brain disorders. The motto of this blog with continue to be "Translating neuroscience research into better care for brain disorders". I believe new brain research tools can lead the way to early diagnosis and treatment. Brain image is an iPad screen shot from the Brain Tutor app.Collins, P., Insel, T., Chockalingam, A., Daar, A., & Maddox, Y. (2013). Grand Challenges in Global Mental Health: Integration in Research, Policy, and Practice PLoS Medicine, 10 (4) DOI: 10.1371/journal.pmed.1001434 Insel, T. (2011). A bridge to somewhere Translational Psychiatry, 1 (4) DOI: 10.1038/tp.2011.4... Read more »
Collins, P., Insel, T., Chockalingam, A., Daar, A., & Maddox, Y. (2013) Grand Challenges in Global Mental Health: Integration in Research, Policy, and Practice. PLoS Medicine, 10(4). DOI: 10.1371/journal.pmed.1001434
hypothesis: Use of recovery periods between weight sets can be used for vision work as form of active recovery to improve strength, vision and recovery technique. ... Read more »
Andersson H, Raastad T, Nilsson J, Paulsen G, Garthe I, & Kadi F. (2008) Neuromuscular fatigue and recovery in elite female soccer: effects of active recovery. Medicine and science in sports and exercise, 40(2), 372-80. PMID: 18202563
Davis WJ, Wood DT, Andrews RG, Elkind LM, & Davis WB. (2008) Elimination of delayed-onset muscle soreness by pre-resistance cardioacceleration before each set. Journal of strength and conditioning research / National Strength , 22(1), 212-25. PMID: 18296978
Micklewright, D., Beneke, R., Gladwell, V., & Sellens, M. (2003) BLOOD LACTATE REMOVAL USING COMBINED MASSAGE AND ACTIVE RECOVERY. Medicine , 35(Supplement 1). DOI: 10.1097/00005768-200305001-01755
Suzuki M, Umeda T, Nakaji S, Shimoyama T, Mashiko T, & Sugawara K. (2004) Effect of incorporating low intensity exercise into the recovery period after a rugby match. British journal of sports medicine, 38(4), 436-40. PMID: 15273179
Globus Pallidus Region of Brain Targeted in DBS in YellowIn a previous post, I summarized some of the highlights of a recent review of Parkinson's disease management by the German neurologists Pedrosa and Timmerman.The first post can be located here and was limited to the drug treatment of the motor symptoms of Parkinson's disease.In part II, I want to focus on deep brain stimulation and the treatment of non-motor symptoms.The authors of the review note the following key points regarding deep brain stimulation:Deep brain stimulation (DBS) therapy for Parkinson's disease is considered most effective when the anatomical target is a small area known as the subthalamic nucleus (STN)STN deep brain stimulation improves all the cardinal symptoms of Parkinson's diseaseHowever, compared to previous DBS targets, STN brings with it new short-term adverse effects including "postoperative dysphoria, hypomania and a higher risk of suicide"Adverse effects of STN-DBS appear greater in older patients making this intervention most effective when used in younger patients with severe motor symptomsAn alternative to STN-DBS is surgery targeting the inferior globus pallidus--this target had been felt by some to be less effective than STN-DBS in treating motor symptomsHowever, globus pallidus DBS is regaining some advocates because it is easier to target and appears to cause less psychiatric and cognitive side effects than STN-DBSGlobus pallidus DBS might be best used in older patients with non-motor symptom predominanceAlthough DBS in Parkinson's disease is generally accepted due to clinical experience with thousands of subjects, there is still some debate on whether to use unilateral or bilateral approaches-the authors favor bilateral treatmentDBS is typically reserved for patients with inadequate response to drug treatment Earlier use of DBS holds promise as a potential boost to quality of lifeA randomized trial of earlier use of DBS, the EARLYSTIM study will soon be published and will be important in providing guidance on the timing of DBSThe decision to use DBS should be made by patients and their families after a comprehensive assessment from an interdisciplinary team of neurologists, neurosurgeons, psychiatrists, physical, occupational and speech therapistsReaders with more interest in DBS for Parkinson's disease may find a recent consensus manuscript on the topic that I have previously reviewed here.The current review also includes a detailed discussion of the treatment of non-motor symptoms including sleep disorders (insomnia, REM sleep behavior disorder and restless leg syndrome), excessive daytime sleepiness, autonomic dysfunction (orthostatic hypotension, gastrointestional motility dysfucntion, and urinary dysfunction), erectile dysfunction, impulse control disorders, medication-induced psychosis, dementia and depression.It outside the scope of this post to review the author's recommendations for management of all of the non-motor symptoms of Parkinson's disease. I did find interesting the author's recommendation for use of low-dose clozapine 12.5 mg to 50 mg or quetiapine 25 to 75 mg at bedtime for the management of psychosis. They also noted donepezil at 5 to 10 mg per day may improve psychosis in patients with Lewy body dementia.Additionally, the review highlighted the use of pramipexole 0.35 to 0.7 mg three times daily for the treatment of depression in Parkinson's disease with lower evidence of the effectiveness for standard tricyclic antidepressants or selective serotonin reuptake inhibitors.Readers with more interest in specific non-motor symptom treatment in Parkinson's disease are directed to the free full text manuscript that can be access by clicking on the reference below.Image of globus pallidus is an iPad screen shot from the app Brain Tutor.Pedrosa, D., & Timmermann, . (2013). Review: management of Parkinson's disease Neuropsychiatric Disease and Treatment DOI: 10.2147/NDT.S32302... Read more »
All you need is love. Or failing that chocolate.And not only because dark chocolate could lower the risk of heart disease, blood pressure and sugar levels. As Dr. Schieberle's team recently discovered that heart could sense and enjoy the sweet smell of chocolate too. When they put small odor-emitting molecules from chocolate on one side of a dish, cells actually moved towards the aroma.The heart, the lungs, the blood, the sperm and testis all have the abilities to recognize chemicals responsible for smells. Genomic studies (Deldmesser et al, 2006) showed that many tissues have working genes responsible for the perception of flavors. Sperm of sea urchines is able to recognize the odor and swim toward the egg. Human sperm might very well be capable of "smelling" their way to the egg too. And white blood cells sense the odors of bacteria to rush to the site of infection in the wound. Unfortunately, cancer cells can also sense their way out of the tumor in the direction of blood vessels, leading to metastasis. Smells can guide social preferences, trigger positive or negative memories, help to lose weight, reduce anxiety or give you nightmares. Smells can make or brake, kill or heal. They can have therapeutic or diagnostic use helping to understand gene-environment health paradigms and paving new avenues for future health care strategies. REFERENCES Feldmesser E, Olender T, Khen M, Yanai I, Ophir R, & Lancet D (2006). Widespread ectopic expression of olfactory receptor genes. BMC genomics, 7 PMID: 16716209Schieberle P, & Molyneux RJ (2012). Quantitation of sensory-active and bioactive constituents of food: A Journal of Agricultural and Food Chemistry perspective. Journal of agricultural and food chemistry, 60 (10), 2404-8 PMID: 22369090Schieberle P., Do cells in the blood, heart and lungs smell the food we eat? 245th Chemistry of Energy and Food, National Meeting & Exposition of the American Chemical Society, New Orleans, LA, April 7-11, 2013... Read more »
Feldmesser E, Olender T, Khen M, Yanai I, Ophir R, & Lancet D. (2006) Widespread ectopic expression of olfactory receptor genes. BMC genomics, 121. PMID: 16716209
Schieberle P, & Molyneux RJ. (2012) Quantitation of sensory-active and bioactive constituents of food: A Journal of Agricultural and Food Chemistry perspective. Journal of agricultural and food chemistry, 60(10), 2404-8. PMID: 22369090
by ebender in Daily Observations
Five psychological scientists, including four APS Fellows, are among the 84 new members and 21 foreign associates elected to the National Academy of Sciences, in recognition of their contributions and The post Four APS Fellows Elected to NAS appeared first on Association for Psychological Science.... Read more »
Aslin, R.N. (2012) Questioning the questions that have been asked about the infant brain using near-infrared spectroscopy. Cognitive Neuropsychology, 29(1-2), 7-33. PMID: 22329690
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