A new animal model has provided insight into the cellular and molecular mechanisms associated with behavioral therapy for depression.  The study, published by Cell Press in the October 9th issue of Neuron, may provide a good model system for testing cellular and molecular interactions between antidepressive medications and behavioral treatments for depression.

Organisms ranging from simple invertebrates to mammals have evolved mechanisms for instinctive and learned fear that are critical for survival.  However, in humans, pathological forms of learned fear can contribute to anxiety disorders, posttraumatic stress, and depression.  “The fact that learned fear can be associated with psychopathologies in humans suggests that this form of learning is not always appropriate and that effective inhibitory constraints are likely to exist,” explains Eric Kandel from Columbia University.

Previous research investigating how learned fear is processed in the brain has made use of a conditioned inhibition learning paradigm wherein an animal is conditioned to associate a target signal with protection from an impending aversive event, resulting in a reduction of conditioned fear.  This process, where an animal learns to take advantage of sources of security in the environment, is thought to represent a form of “learned safety.”

Daniela Pollak in the Kandel lab was interested in attempting to characterize some of the behavioral consequences of learned safety as well as exploring the phenomenon at the molecular level.  She observed that learned safety reduced depression-like behavior in mice in a manner that was comparable to that seen with pharmacological antidepressants.  Consistent with the behavioral antidepressant effects, learned safety also shared neurobiological hallmarks associated with other antidepressant therapies.  Specifically, learned safety promotes the survival of newborn nerve cells and expression of critical growth factors in the hippocampus.

The researchers went on to search for differentially regulated genes in the amygdala of safetyand fear-conditioned mice.  The amygdala is a brain region associated with emotional symptoms that are a hallmark of depression.  Learned safety led to decreased expression of genes involved in dopamine and substance P signaling, but not serotonin signaling.  This is significant because serotonin receptors are a major target of popular antidepressant medications.

“We propose a model in which the stress-reducing and antidepressant effects of learned safety are mediated through the interaction of (at least) two different neurotransmitter systems.  Our findings suggest that learned safety is an animal model of a behavioral antidepressant that shares some of the neuronal modifications typical of pharmacological antidepressant, but is mediated by different molecular pathways,” offers Kandel.

Exposure to Bisphenol A (BPA), phthalates and flame retardants (PBDEs) are strongly associated with adverse health effects on humans and laboratory animals.  A special section in the October 2008 issue of Environmental Research, “A Plastic World” provides critical new research on environmental contaminants and adverse reproductive and behavioral effects.

Plastic products contain “endocrine disrupting chemicals” that can block the production of the male sex hormone testosterone (phthalates used in PVC plastic), mimic the action of the sex hormone estrogen (bisphenol A or BPA used in polycarbonate plastic), and interfere with thyroid hormone (brominated flame retardants or PBDEs used in many types of plastic).

Two articles report very similar changes in male reproductive organs in rats and humans related to fetal exposure to phthalates.  Two articles show that fetal exposure to BPA or PBDEs disrupts normal development of the brain and behavior in rats and mice.  Two other articles provide data that these chemicals are massively contaminating the oceans and causing harm to aquatic wildlife.

The other studies integrate new laboratory research with a broader view reflecting exposures to a variety of chemicals in plastic.  These ubiquitous chemicals found in many plastics act independently and together to adversely affect human, animal and environmental health.

The articles show amongst others the massive contamination of the Pacific Ocean with plastic, and the amount of contamination has increased dramatically in recent years; animal brain structure, brain chemistry and behavioral effects from exposure to BPA and “phthalate syndrome” in rats’ male offspring.

“For the first time a series of articles will appear together that identify that billions of kilograms of a number of chemicals used in the manufacture of different types of plastic can leach out of plastic products and cause harm to the brain and reproductive system when exposure occurs during fetal life or prior to weaning,” emphasized Dr. Frederick vom Saal, Guest Editor of the “Plastic World”.

“Not only are these studies of scientific importance, they also contribute to the ongoing US congressional hearings involving the Food and Drug Administration,” remarked Gert-Jan Geraeds, Publisher of Environmental Research, “As such, “The Plastic World” has a broader societal impact and raises awareness of increasingly important environmental issues”.

Some animal species have developed conspicuous traits produced by melanin pigments (for instance, dark manes in lions, black stripes in some birds and fishes).  These traits are used as signals during contests for resources and/or contribute to increase the mating opportunities.  However, the efficiency of these traits as signals depends on the fact that they transmit honest information about the quality of the bearer.  This would be only assured by the fact that producing or maintaining the signal inevitability implies a cost.  Thus, only those individuals able to afford the cost would also be able to conveniently express the signal.

Signals produced by melanin pigments have challenged our understanding because they are apparently cost-free and strongly controlled by the genotype.  Melanin pigments are not as limited in production as carotenoids, yellow-red pigments common in vertebrates and only obtained from certain food items.  In fact, melanin is constructed from amino acids present in proteins of the organism.  However, recent experimental studies have become to disentangle the cost at the basis of melanin-based signals.

A recent article by Ismael Galván at the Museo Nacional de Ciencias Naturales (CSIC) in Madrid and Carlos Alonso-Alvarez at IREC-CSIC, Spain, published in the online, open-access journal PloS ONE proposes a novel hypothesis suggesting that these traits could indicate the ability of the bearer in fighting free radicals and oxidative damage.  On the basis of medical bibliography, the researchers realized that tissue melanization is constrained in the presence of high enough levels of a key intracellular antioxidant named glutathione, which is considered one of the most powerful antioxidants present in virtually all animal cells.

The scientists hypothesized that low levels of this substance are also required to express melanin-based signals present in many animals.  This implies that individuals able to express these signals should be also able to fight off an oxidative challenge, as a consequence of the low levels of the cited antioxidant.  Only those animals with alternative antioxidant resources would be able to afford the cost of signaling.  By chemically inhibiting the production of glutathione at the red blood cells, authors were able to significantly increase the size of a black stripe present in the feathers of the breast of great tits (a common garden bird).  This stripe is a conspicuous trait playing a significant role during combats for territory, food or mates.

Furthermore, the reduction of glutathione levels also induced a mobilization of other antioxidant molecules to the blood plasma, supporting the cost, such as hypothesized by Alonso-Alvarez and colleagues.

The melodious singing of birds has been long appreciated by humans, and has often been thought to reflect a particularly positive emotional state of the singer.  In a new study published in the online, open-access journal PloS ONE on October 1, researchers at the RIKEN Brain Science Institute in Japan have demonstrated that this can be true.  When male birds sang to attract females, specific “reward” areas of their brain were strongly activated.  Such strong brain activation resulted in a similar change in brain reward function to that which is caused by addictive drugs.

The brain of humans and other animals is programmed to have a positive emotional response to rewarding stimuli, such as food or sex.  A critical part of this reward signal is thought to be provided by increased activity of neurons containing dopamine in the brain ventral tegmental area, VTA.  Along with natural rewards, the same brain circuits can also be strongly activated by artificial rewards such as addictive drugs.  Previous studies in mammals have found that after animals are given drugs such as cocaine or amphetamine, the strength of synaptic connections onto dopamine neurons in VTA is strongly increased, or potentiated.  Such potentiation has been suggested to be an important long-lasting adaptation of brain function caused by drug use, and involved in maintenance of addictive behavior.

Whether such potentiation can also be caused by more natural rewards has been less studied.  Social interactions with others are critical for normal healthy life, and therefore should be rewarding for humans and also for other animals.  In the new study in PloS ONE, Ya-Chun Huang and Neal Hessler of the Vocal Behavior Mechanisms Lab examined one specific social behavior, courtship singing of songbirds.  In the zebra finch, an Australian songbird, males sing in two different situations.  Most importantly, males sing “directed song” during courtship of females.  When males are alone, they produce “undirected song”, possibly for practice or to communicate with birds they can’t see.  A previous study by this research group showed that only when males sang to attract a female, but not when they sang while alone, many unidentified neurons in the VTA were strongly activated.

Huang and Hessler now show, in the current study, that such a natural social interaction, singing to a female, can cause the same kind of synaptic potentiation of VTA dopamine neurons as use of addictive drugs, while singing solo did not affect these neurons.  Further study of this system should give insight into how both natural and artificial rewards interact with each other, and specifically how damage to brain reward systems during addiction can disrupt processing of natural rewards such as social interaction.

This study also provides the clearest evidence so far that singing to a female is rewarding for male birds.  This may not be surprising, as such courtship is a necessary step in producing offspring, and so should be a positive experience.  Other studies have provided some evidence that in mammals, including humans, sexual behavior and attachment (as well as rewarding aspects of video games and chocolate) also depend on the same brain reward areas and dopamine.  So, despite the distant evolutionary relationship between birds and humans, it may be that during such intense social interactions as courtship, both share some similar emotional state.

The way male managers power dress, posture and exercise power is due to humans’ evolutionary biology, according to research from the University of New South Wales (UNSW).

Prehistoric behaviours, such as male domination, protecting what is perceived as their “turf” and ostracising those who do not agree with the group is more commonplace in everyday work situations than many of us want to accept, according to the research which was carried out in hospitals.

“This tribal culture is similar to what we would have seen in hunter gather bands on the savannah in southern Africa,” says the author of the paper, Professor Jeffrey Braithwaite, from UNSW’s Institute for Health Innovation.

“While this research focuses specifically on health care settings, the results can be extrapolated to other workplaces,” says Professor Braithwaite.

“Groups were territorial in the past because it helped them survive.  If you weren’t in a tight band, you didn’t get to pass on your genes,” he says.  “Such tribalism is not necessary in the same way now, yet we still have those characteristics because they have evolved over two million years.

“It’s a surprise just how hard-wired this behaviour is,” says Professor Braithwaite.  “It’s predictable that a group will ostracise a whistleblower, for instance.  It’s not good, but it’s understandable in the tribal framework.  It explains all sorts of undesirable behaviours, including bullying.”

Professor Braithwaite’s research is based on hundreds of interviews and observations of health workers over a 15-year period.  He used an evolutionary psychology approach – incorporating archaeology and anthropology of the earliest known humans – to compare with modern behaviours.

It is hoped the research can be used to develop strategies to encourage clinical professionals to work together more effectively.

“We need to stop being simplistic and realise that changing behaviours and encouraging teamwork is much harder than we think,” says Professor Braithwaite.  “Getting different groups together and talking through some of the differences, and appreciating some of the unwritten rules which drive people, are crucial steps in improving trust.

“We also need to re-think education.  We train doctors in a completely different arena from nurses and allied health staff, then we bring them together in the workplace after they graduate and expect everyone to be team players,” he says.  “We need to bring them together much earlier in the educational process.”

Other features include:

* Meetings are held in the most senior manager’s office, who typically dominates proceedings

* Managers do not spend as much of their time as people think sitting reading quietly, or attending to paperwork in front of a computer.  They are out there manoeuvring and positioning at meetings, one-on-one encounters and coffee cliques.

* Managers rarely take lunch or tea breaks

* Non-managerial staff regularly take an allocated period of time for breaks

We all know that people can be influenced in complex ways by their peers.  But two new studies in the September 11th issue of Current Biology, a Cell Press publication, reveal that the same can also be said of fruit flies.

The researchers found that group composition affects individual flies in several ways, including changes in gene activity and sexual behavior, all mediated by chemical communication.

“Many take for granted that communication among insects is hard-wired,” said Joel Levine of the University of Toronto Mississauga.  “We have observed that communication may be influenced by relationships even in insects like fruit flies, which have not been traditionally considered to be social insects.  We have seen individual responses that appear to be altered quickly–within a day of joining a group.  This level of spontaneity or plasticity is complex because it occurs on many levels: involving neural and non-neural tissues, changes in gene expression and physiology, and changes in behavior, all of which are inter-related.”

That connection between an individual and its environment, both social and otherwise, reveals a depth that is often missing in experiments that focus exclusively on one or the other, he said.

In one study, the researchers reveal that specialized cells of the fly called oenocytes, which produce chemical signals known as pheromones, operate according to an internal circadian clock.  However, the “ticking” of that clock varies depending upon the social environment the flies find themselves in: Males in mixed company—meaning in the company of other flies that were less similar at the genetic level—produced different chemical signals than did males in genetically uniform group, they found.

Those signals had a clear effect on behavior: flies in genetically more mixed social groups had more sex than those in more uniform groups did.

To further explore the connection between chemical communication amongst fruit flies and their physical and social environments, the researchers examined in a second study the chemical composition of pheromones produced by flies in mixed versus homogeneous groups.  Those tests were conducted in flies under conditions of constant darkness and in those under a normal light-dark cycle.

Their results showed important effects on flies of both the physical and social environment.  Moreover, they found a strong interaction between the genetic background of individual flies and their social environments.

“The response of an individual male to others like him depends on his neighbors,” Levine said.  “That response is quite specific because it affects some of the chemicals made by a fly, but not others.”

The results suggest that chemical communications is a rather “fickle” trait, depending heavily on the influence of a fly’s peers.

The findings also challenge the traditional view of the relationship between behavior and the underlying mechanisms that control that behavior, Levine noted.

“The bottom line is that membership in the same social group trumps genotype as a predictor of chemical displays,” he said.  “At a general level the surprise comes from appreciating that molecular function is altered by behavior.  Behavior is not only the product of molecular mechanisms, it is also a player in those mechanisms.”

A new study suggests that although humans may have developed complex thought processes that can help to regulate their emotions, these processes are linked with evolutionarily older mechanisms that are common across species.  The research, published by Cell Press in the September 11th issue of the journal Neuron, provides new insight into way the brain manages fear and may guide exploration of novel pharmacological and therapeutic treatments for anxiety disorders.

“The ability to eliminate, control or diminish negative emotional responses is important for adaptive function and critical in the treatment of psychopathology,” says study author, Dr. Mauricio Delgado from Rutgers University.  “Recent research examining the neural mechanisms for diminishing fears has focused on two techniques: extinction, which has been explored across species, and cognitive emotion regulation strategies, which are unique to humans.”  Previous work in rodents and humans has implicated activity in the amygdala and ventral medial prefrontal cortex (vmPFC) in extinction.  In contrast, neural circuits underlying cognitive strategies to regulate emotions are not as well understood.

Dr. Delgado, Dr. Elizabeth A. Phelps from New York University, and their colleagues were interested in examining the similarities and differences of diminishing fear through both techniques.  They used similar experimental paradigms with different means of controlling fear to directly compare the neural mechanisms that mediate extinction and emotional regulation.  A typical fear conditioning method was paired with a measurement of physiological arousal to examine extinction, while a cognitive emotion regulation strategy was also implemented.  Functional magnetic resonance imaging (fMRI) was used to compare the neural activation patterns of extinction and emotional regulation.

The researchers observed that the lateral prefrontal cortex regions engaged by cognitive emotion regulation strategies influenced the amygdala and diminished fear through similar vmPFC connections that are thought to inhibit the amygdala during extinction.  Taken together, the findings indicate that there is overlap in the neural circuitry of diminishing learned fears through emotion regulation and extinction and that vmPFC may play a general regulatory role in diminishing fear across a range of paradigms.

“Our results suggest that even though humans may have developed unique capabilities for using complex cognitive strategies to control emotion, these strategies may influence the amygdala through phylogenetically shared mechanisms of extinction,” explains Dr. Phelps.  “Extinction and cognitive emotion regulation may be, in part, complementary in that they rely on a common neural circuitry and, perhaps, similar neurophysiological and neurochemical mechanisms.”

New research identifies a few critical neurons that initiate sex-specific behaviors in fruit flies and, when masculinized, can elicit male-typical courtship behaviors from females.  The study, published by Cell Press in the September 11th issue of the journal Neuron, demonstrates a direct link between sexual dimorphism in the brain and gender differences in behavior.

In the fruit fly, Drosophila melanogaster, males display a series of complex and stereotypic behaviors when they are courting a female.  Males chase the female while vibrating their wings, producing a love song that has an aphrodisiac influence on the female, who would otherwise take action to escape the male’s advances.  Later steps in the male courtship behavior involve the initiation and completion of copulation.

“Although previous studies have identified a few key brain areas, such as the dorsal posterior brain, that appear to play a pivotal role in initiating male sexual behavior, nothing is known about the identity of neurons and their circuits in the brain sites which are central to the generation of male courtship behavior,” says lead study author Professor Ken-ichi Kimura of the Hokkaido University of Education in Japan.

Professor Kimura and colleagues made use of a sophisticated technique that allowed them to identify, manipulate, and study small groups of cells in the fruit fly brain.  The researchers focused on neurons that expressed a gene called fruitless (fru), a known sex-determination gene.  The male-specific Fru protein is expressed in the brains of male flies, but not females.  Studies have indicated that fru functions in parallel with another sex-determination gene called doublesex (dsx) and that fru may function as a kind of master control gene to direct organization of brain centers for sexual behavior.

A fru/dsx-expressing cell cluster, known as P1, was identified as an important site for initiating male courtship behavior.  P1 cells are fated to die in females through the action of a feminizing protein called DsxF.  Interestingly, genetic manipulation of females so that they possessed male P1 neurons effectively provoked male-typical courtship behavior in the females, even when other parts of the brain were not masculinized.

“P1 is located in the dorsal posterior brain and is composed of 20 neurons that have projections which communicate with the bilateral protocerebrum,” explains Professor Kimura.  “We found that the masculinizing protein Fru is required in the male brain for correct positioning of the projections from the P1 neurons.”

Taken together, these findings demonstrate that the coordinated action of sex-determination genes dsx and fru confer the unique ability to initiate male-typical sexual behavior on P1 neurons.  This research represents one of only a few examples presenting direct evidence for sexually dimorphic mechanisms that underlie gender-specific behavior and is the first to identify a specific cluster of cells that initiate courtship.

You can tell a lot about people from the way they move alone: their gender, age, and even their mood, earlier studies have shown.  Now, researchers reporting in the September 9th issue of Current Biology, a Cell Press publication, have found that observers perceive masculine motion as coming toward them, while a characteristically feminine walk looks like it’s headed the other way.

Such studies are done by illuminating only the joints of model walkers and asking observers to identify various characteristics about the largely ambiguous figures.

“It’s a really interesting thing,” said Rick van der Zwan of Southern Cross University in Australia.  “If you look at someone with just their joints illuminated when they aren’t moving, it’s difficult to tell what it is you are looking at.  But as soon as they move, instantaneously, you can tell that it’s a person and perceive their nature.  You can tell if it’s a boy or a girl, young or old, angry or happy.… You can discern all these qualities about their state, affect, and actions with no cues at all about what they look like—with no form at all, just motion.”

Many previous studies of biological motion perception have relied on male figures as models, van der Zwan said.  One of those earlier studies had noticed an interesting phenomenon: even though you can’t really tell whether a so-called point-light figure is facing toward you or away, people seemed to perceive those figures always as facing in their direction.

Now, van der Zwan and his colleagues show that this isn’t always true.

In their study, they allowed people to observe point-light figures representing a continuum from an extremely “girly girl” to a “hulking male.”  At the halfway point in between was a gender-neutral walker that observers judged as male half the time and female half the time.

Their results showed that walking male figures did indeed appear to face toward you.  Female figures, on the other hand, seemed as though they faced away.  The results are the first to show a link between the perception of gender from biological motion cues and the perception of orientation.

That same pattern emerged regardless of the gender of the person watching, a finding that van der Zwan considers an important clue about the behavior.

“Our data suggest that biological motion is an important cue for social organisms trying to operate in environments where other cues as to the actions or intentions of other organisms may be ambiguous,” the researchers wrote.  “Whilst the precise role of local cues in mediating these effects requires further explication, it is tempting to speculate that the orientation biases reported here reflect the development of perceptual mechanisms that weigh in the probable cost of misinterpreting the actions and intentions of others.  For example, a male figure that is otherwise ambiguous might best be perceived as approaching to allow the observer to prepare to flee or fight.  Similarly, for observers, and especially infants, the departure of females might signal also a need to act, but for different reasons.”