The smell of an alpha male....

Pheromones influence sexual behavior and reproduction in rodents. Mak et al report that:

...the pheromones of dominant (but not subordinate) males stimulate neuronal production in both the olfactory bulb and hippocampus of female mice, which are independently mediated by prolactin and luteinizing hormone, respectively. Neurogenesis induced by dominant-male pheromones correlates with a female preference for dominant males over subordinate males, whereas blocking neurogenesis with the mitotic inhibitor cytosine arabinoside eliminated this preference. These results suggest that male pheromones are involved in regulating neurogenesis in both the olfactory bulb and hippocampus, which may be important for female reproductive success.

I keep wondering if we won't be finding evidence for a version of this effect (perhaps more subtle) in humans... would the cheerleader, like the female rat in the box below, be more likely to hang out with the star quarterback if she had smelled his sweaty jersey a day earlier??

An illustration from the summary review by DiRocco and Xia:

Figure legend: Dominant male pheromones stimulate neurogenesis in females.
(a) Female mice exposed to dominant male pheromones spent more time sniffing the dominant male, whereas females exposed to subordinate male pheromones did not show any preference. (b) Exposing female mice to pheromones from dominant males led to increased neurogenesis in the subventricular zone (SVZ) and dentate gyrus (DG). Pheromones signal the main olfactory epithelium (MOE)–main olfactory bulb (MOB) axis, which relays the signal to the hypothalamus (HYP)–pituitary (PIT) axis, leading to the release of luteinizing hormone (LH) and prolactin (PRL). LH appeared to stimulate neurogenesis in the dentate gyrus of the hippocampus, whereas prolactin induced neurogenesis in the SVZ and MOB. It is hypothesized that pheromone-induced neurogenesis may underlie female mating preference for the dominant male. NC, nasal cavity; RMS, rostral migratory stream; green circles, newborn neurons.

Mistakes were made...Cognitive Dissonance Theory

William Swann reviews the book by Tavris and Aronson "Mistakes Were Made (But Not By Me): Why We Justify Foolish Beliefs, Bad Decisions, and Hurtful Acts." On cognitive dissonance theory:

..the authors' version is that people's brains are wired to find consistency between what they do and their positive images of themselves. Presumably this is why people engage in a wide array of mental gymnastics to salvage their self-esteem rather than own up to their mistakes. The typical outcome is that people twist the truth to make it seem kinder or more flattering than it actually is. In extreme cases, they may engage in distortion and denial of objective reality...dissonance theory can explain many laboratory findings and elements of many naturally occurring phenomena. For example, the authors maintain that when ordinary people blithely agreed to administer dangerously strong electric shocks to hapless learners in Stanley Milgram's classic experiments, the subjects' penchant for self-justification ("the experimenter told me to continue") was a key contributor to their complicity. Similarly, in instances in which prosecutors have refused to back down when DNA evidence has revealed that a defendant was wrongfully sentenced for a crime, Tavris and Aronson attribute theprosecutors' refusal to admit error to pernicious self-justification processes. The authors also maintain that most champions of the repressed-memory movement, when confronted with information suggesting that the "memories" of alleged victims are false, simply dismiss the evidence as being a form of backlash against child victims and incest survivors...As the book's title suggests, one of the topics touched on is contemporary politics. Tavris and Aronson mention in the endnotes that many U.S. presidents have used the phrase "mistakes were made," including Bill Clinton, Ronald Reagan and Richard Nixon. Although Alberto Gonzales's use of the phrase a few months ago ("I acknowledge that mistakes were made here") occurred too recently to make it into the book, the authors do discuss some of the self-justifications and self-deceptions of the current administration. For example, they characterize George W. Bush as "the poster boy for 'tenacious clinging to a discredited belief.'"

The evil that men do - The Lucifer Effect

Robert Levine reviews the recent book "The Lucifer Effect: Understanding How Good People Turn Evil," by Philip Zimbardo, the man who did the famous Stanford Prison Experiment that has become a cornerstone of social psychology (PDF of review here).

The 1971 Stanford Prison Experiment, in which subjects (ordinary college-age men) were assigned to play the role of a prisoner or guard, demonstrated that situations may be more powerful than personality traits in affecting behavior. Subjects playing the role of guards in the Stanford Prison Experiment were quickly transformed into abusers. This scene eerily evokes the photos taken decades later by the guards at Abu Ghraib prison in Iraq.

A clip from the review:

What, Zimbardo asks, leads ordinary people to do bad things, things they never would have imagined doing? Most evildoing, it becomes depressingly clear, is driven by rather ordinary social-psychological reactions. Zimbardo offers an extensive list and discussion of the toxic situational forces and normal psychological reactions to them that tend to activate the Lucifer effect. He provides a detailed, intelligent and workable program for resisting unwanted social influence, highlighting dangers and offering tangible prescriptions for neutralizing negative effects. There are, for example, mini-tutorials on how to distinguish between just and unjust authorities, on being careful not to sacrifice one's freedom for the illusion of security, and on learning to recognize when, where and how to stand up to unjust systems.

The final chapter is a gem. Here Zimbardo seamlessly demonstrates how the same social psychology that may exploit our worst instincts can be reconstrued to cultivate the best in ourselves. Altruism, like evil, is readily responsive to situational forces, and Zimbardo suggests strategies for tapping into these potentialities. He also presents a provocative, multidimensional taxonomy of heroism that I hope will stimulate long-overdue research and education in this area.

Why Men Matter: Mating Patterns Drive Evolution of Human Lifespan

Tuljapurkar et al. present an interesting model for why human lifespan continues well past the age of menopause in women.. even though women no longer reproduce, older men still mate with younger women, and natural selection favors survival for as long as men reproduce (that is, there is a selective force against deleterious autosomal mutations at ages well past menopause). Here is their abstract, you should check the figures in the paper....

Evolutionary theory predicts that senescence, a decline in survival rates with age, is the consequence of stronger selection on alleles that affect fertility or mortality earlier rather than later in life. Hamilton quantified this argument by showing that a rare mutation reducing survival is opposed by a selective force that declines with age over reproductive life. He used a female-only demographic model, predicting that female menopause at age ca. 50 yrs should be followed by a sharp increase in mortality, a “wall of death.” Human lives obviously do not display such a wall. Explanations of the evolution of lifespan beyond the age of female menopause have proven difficult to describe as explicit genetic models. Here we argue that the inclusion of males and mating patterns extends Hamilton's theory and predicts the pattern of human senescence. We analyze a general two-sex model to show that selection favors survival for as long as men reproduce. Male fertility can only result from matings with fertile females, and we present a range of data showing that males much older than 50 yrs have substantial realized fertility through matings with younger females, a pattern that was likely typical among early humans. Thus old-age male fertility provides a selective force against autosomal deleterious mutations at ages far past female menopause with no sharp upper age limit, eliminating the wall of death. Our findings illustrate the evolutionary importance of males and mating preferences, and show that one-sex demographic models are insufficient to describe the forces that shape human senescence.

Male fertility in 1980 France (black), Pakistan 1984 (blue dots) and Cameroon 1964 (red dashes). Cameroon's distribution is common of high-fertility polygynous societies. The Y-axis shows age-specific fertility rates as a fraction of the total fertility rate.

Chicago Art Institute - Garden Restaurant

I thought I would say hello from the middle of an annual mini-vacation to Chicago, staying with old friends and visiting the Art Institute.

More on "The Political Brain"

As a followup on my Oct. 23 and July 11 posts on neuroimaging during political decisions I would like to point out David Brooks' review of Westen's book "THE POLITICAL BRAIN - The Role of Emotion in Deciding the Fate of the Nation." He suggests that Westen - even granted that he does a convincing job of showing how emotions can color political decisions - goes overboard in essentially suggesting that appeals to rationality should be thrown out altogether.

Westen:

...assert(s) that Democrats have been losing because they have been appealing to the rational part of the mind. They issue laundry lists of policies and offer arguments with evidence. They don’t realize how the images they are presenting set off emotional cues that undermine their own campaigns...For example, the right side of John Edwards’s mouth tends to curl up. “Humans innately dislike facial asymmetries,” Westen observes, “and this should have caught the eye of his advisers.” In Connecticut, Ned Lamont ran a commercial showing Joe Lieberman morphing into George Bush, but in the ad Lieberman was smiling. “Smiling faces innately activate parts of the brain (and facial mimicry on the part of the observer) that reinforce happiness, not distaste.”..Republicans...,are brilliant at using words and images that set off emotional cascades. Ronald Reagan used the word “confiscation” in reference to taxation, and was able to persuade people to agree to lower taxes. He called Nicaraguan contras “freedom fighters” and was able to secure them funding.

Brooks suggests:

The core problem with Westen’s book is that he doesn’t really make use of what we know about emotion. He builds on the work of Antonio Damasio, without applying Damasio’s conception of how emotion emerges from and contributes to reason...In this more sophisticated view, emotions are produced by learning. As we go through life, we learn what cause leads to what effect. When, later on, we face similar situations, the emotions highlight possible outcomes, drawing us toward some actions and steering us away from others...In other words, emotions partner with rationality. It’s not necessary to dumb things down to appeal to emotions. It’s not necessary to understand some secret language that will key certain neuro-emotional firings. The best way to win votes — and this will be a shocker — is to offer people an accurate view of the world and a set of policies that seem likely to produce good results.

Discontinuities between Human and Animal Cognition

Premack offers a stimulating brief essay (PDF here) pointing out that recent cognitive studies finding abilities in animals once thought unique to humans should not lead us to confuse similarity with equivalence, for the human brain has nerve cell types and connections not found in any other animals. He examines eight cognitive areas to argue that dissimilarities are large. Here is his abstract:

Microscopic study of the human brain has revealed neural structures, enhanced wiring, and forms of connectivity among nerve cells not found in any animal, challenging the view that the human brain is simply an enlarged chimpanzee brain. On the other hand, cognitive studies have found animals to have abilities once thought unique to the human. This suggests a disparity between brain and mind. The suggestion is misleading. Cognitive research has not kept pace with neural research. Neural findings are based on microscopic study of the brain and are primarily cellular. Because cognition cannot be studied microscopically, we need to refine the study of cognition by using a different approach. In examining claims of similarity between animals and humans, one must ask: What are the dissimilarities? This approach prevents confusing similarity with equivalence. We follow this approach in examining eight cognitive cases—teaching, short-term memory, causal reasoning, planning, deception, transitive inference, theory of mind, and language—and find, in all cases, that similarities between animal and human abilities are small, dissimilarities large. There is no disparity between brain and mind.

Another major article on this topic is in draft form for Brain and Behavioral Sciences: "Darwin’s mistake: explaining the discontinuity between human and nonhuman minds," by Derek C. Penn, Keith J. Holyoak and Daniel J. Povinelli.
Their abstract:

Over the last quarter-century, the dominant tendency in comparative cognitive psychology has been to emphasize the similarities between human and nonhuman minds and to downplay the differences as “one of degree and not of kind” (Darwin 1871). In the present paper, we argue that Darwin was mistaken: the profound biological continuity between human and nonhuman animals masks an equally profound discontinuity between human and nonhuman minds. To wit, there is a significant discontinuity in the degree to which human and nonhuman animals are able to approximate the higher-order, systematic, relational capabilities of a physical symbol system (Newell 1980). We show that this symbolic-relational discontinuity pervades nearly every domain of cognition and runs much deeper than even the spectacular scaffolding provided by language or culture alone can explain. We propose a representational-level specification of where human and nonhuman animals’ abilities to approximate a PSS are similar and where they differ. We conclude by suggesting that recent symbolic-connectionist models of cognition shed new light on the mechanisms that underlie the gap between human and nonhuman minds.

Evolution of the upturned palm

Tierney writes a brief article in the Aug. 28 NYTimes science section on thinking about ancient origins of the "can you spare me a dime" upturned palm, noting that the upturned palm is a submissive gesture:

...a “gestural byproduct” of the circuits in the brain and spinal cord that protected vertebrates hundreds of millions of years ago..Confronted with a threat, ancient lizards would instinctively bend their spine and limbs to press their bodies closer to the ground, protecting the neck and head and signaling submission to a larger animal. This crouch display is the opposite of the high-stand display, the aggressive posture of a stallion or a gorilla raising its chest and head to appear larger...The human remnant of the crouch display is a shrug of the shoulders, which lowers the head and rotates the forearms outwards so that the palms face up. Conversely, the high-stand display persists in humans as a rotation of the forearms and palms in the opposite direction, producing the domineering palm-down gesture used by a boss slapping the conference table or an orator commanding quiet from his audience.

The Emory University group (Franz de Waal et al.) have found that Chimps and Bonobos use the palm-up gesture in a much more flexible way (depending on the situation and group) that vocalizations and facial expression (more strongly tied to emotions). This leads to speculation that gestures may have served as the steppingstone for early hominid communication and, possibly, language.

fMRI feedback for pain reduction

Jason Pontin discusses Omneuron and other start-ups that propose to teach sufferers to think away their pain...and... similarly treat addiction, depression and other intractable neurological and psychological conditions (PDF here).

Prokofiev Ballade for Cello and Piano

In this video Sonny Enslen (cello) and I are doing a final rehearsal before doing this piece for two amateur music performance groups in Madison Wisconsin: Carnaval and Allegro. The piano is a Steinway B at my Twin Valley, Middleton WI, home, freshly tuned and voiced.

Calisthenics for the aging mind.

I'll pass on this reasonably written NYTimes article by Christine Larson (PDF here) about software products promising brain enhancement for those of us who fret about our aging brains.

Permanent amygdala changes in people close to 9/11 attack

I'm passing on this brief piece pointed out to me by blog reader Scott Rosenblum, from Scientific American Mind. Readers will recall that the amygdala is the part of the brain that regulates emotional intensity and creates emotional memories. One clip:

In the Cornell study, functional magnetic resonance imaging (fmri) scans showed that people within two miles of the site that day have a hyperactive amygdala as compared with people who lived 200 miles away, even though those nearby were seemingly resilient and show no signs of mental disorder. The N.Y.U. team similarly found that when asked to recall the events of 9/11, twice as many people who were near Ground Zero had elevated amygdala activity as compared with people who were five miles away in midtown Manhattan. Slow recovery of a highly active amygdala, the Cornell researchers say, could increase susceptibility to mental health problems later in life.

By the way, Scientific American Mind is issued monthly, some of the brief articles you can read, others require a digital subscription (which I have been too stingy to spring for.)

The topography of fear

Mobbs and colleagues have devised an ingenious experiment to evaluate how different neural circuits in the human brain are engaged by distal and proximal threats. From the review of this work by Maren:

Mobbs and colleagues developed a computerized virtual maze in which subjects are chased and potentially captured by an "intelligent" predator. During the task, which was conducted during high-resolution functional magnetic resonance imaging (fMRI) of cerebral blood flow (which reflects neuronal activity), subjects manipulated a keyboard in an attempt to evade the predator. Although the virtual predator appeared quite innocuous (it was a small red circle), it could cause pain (low- or high-intensity electric shock to the hand) if escape was unsuccessful. Brain activation in response to the predatory threat was assessed relative to yoked trials in which subjects mimicked the trajectories of former chases, but without a predator or the threat of an electric shock....the prefrontal cortex and lateral amygdala were strongly activated when the level of threat was low, and this activation shifted to the central amygdala and periaqueductal gray when the threat level was high.

Models of consciousness at ASSC

By now I've made a number of references to the June 22-25 meeting of the Association for the Scientific Study of Consciousness in Las Vegas. Stuart Hameroff has just offered a report (PDF here) on the conference in the Journal of Consciousness Studies. His discussion of 'local' versus 'global' connection models of consciousness is worth excerpting here:

Dennett...reiterated one key feature of his multiple drafts model, that
activity anywhere in the brain could elicit consciousness, as long as
that particular activity was more than activity in any other brain area at
that moment. When asked precisely what type of neural activity did
the trick, Dennett passed. Put both Gazzaniga and Dennett in the ‘local’
camp (apparently with Christof Koch, who took that position in
last year’s ASSC debate). The globalists came later.

Koch (ASSC’s scientific compass) and most neuroscientists
assume axonal firings, or spikes are the bit-like currency underlying
the NCC. Gamma synchrony (coherent 30 to 90 Hz EEG, a.k.a.
‘coherent 40 Hz’) and other EEG are generated not by spikes, but by
dendritic local field potentials (LFPs), a distinction addressed in two
excellent posters from David Leopold’s NIMH group. Recording both
spikes and LFPs in monkey cortex and thalamus, they found that subjective
awareness correlates with dendritic LFPs rather than axonal
spikes.

Are dendrites and gamma synchrony outside ASSC’s narrow
focus? After Singer discovered gamma correlations with consciousness
in the 1980s, Francis Crick and Christof Koch helped launch the
gamma synchrony NCC bandwagon. But they later jumped ship,
along with many others, related to an influential analysis by Shadlen
and Movshon which rejected gamma synchrony. Gamma synchrony
was rejected not because it doesn’t correlate with consciousness — it
clearly does — but because it doesn’t jive with axonal spikes, the
anointed currency of the NCC. Gamma synchrony EEG derives from
LFPs, in turn derived from post-synaptic dendritic potentials. Forced
to choose between dendritic synchrony and axonal spikes as the NCC,
Shadlen and Movshon, Crick and Koch and many others chose spikes,
and ASSC followed. Too bad.

LFPs and gamma synchrony occur both locally and globally,
compatible with both local origin theories, and global/hierarchical
views like Global Workspace (GW) and HOT. With GW guru Bernie
Baars in the house, global hierarchies surfaced in the superb session
‘Cortical Networks and Conscious Awareness’ with Alumit Ishai
(Zurich), Rafael Malach (Israel) and Giulio Tononi (Wisconsin).

Tononi, more suave than even Koch, claimed that effective connectivity
(measurable through EEG/LFPs) in thalamocortical circuits
correlates with consciousness. Tononi used transcranial magnetic
stimulation on himself, among others, to see how it disrupted normal
sleep. (What an interesting college roommate he could have been!)
Put Tononi in the globalist camp.

Alumit Ishai used fMRI to study face recognition. She found
activity in a feed-forward (posterior to frontal) hierarchical network,
including posterior visual, limbic/emotional and frontal cortex. Put
Ishai in the globalist camp (along with Koch — now in both camps —
whose tutorial covered ‘top-down’, frontal to posterior, attention
mechanisms).

So … does consciousness require hierarchical organization as the
globalists and HOT proponents advocate? Or are the localists correct
in that consciousness can erupt in any sufficiently active brain region?
Rafael Malach from the Weizman Institute in Israel addressed this
issue. He studied continuous fMRI in subjects watching Sergio
Leone’s epic spaghetti Western The Good, the Bad and the Ugly,correlating
specific fMRI activity with precise movie scenes and frames.
While viewing the film, all above-baseline fMRI activity remained
posterior in the subjects’ visual cortical areas, with occasional snippets
of activity in sensory cortex. Malach showed that the appearance
of faces in the film (Clint Eastwood, Lee van Cleef, Eli Wallach) corresponded
with activity in viewers’ posterior visual cortex face
regions. Activity in the ‘hand’ area of sensory homunculi occurred
precisely during scenes/frames showing characters’ hands gripping a
gun, cigar or dealing cards.

Without posterior-frontal connections, Malach suggested lateral
links among basal dendrites of layer 5 pyramidal cells and cortical
interneurons worked in a distributed, rather than hierarchical,
LFP-friendly architecture to produce conscious experience. Put
Malach in his own camp — not local but not necessarily global. Call it
lateral/distributed.

Could local, global and/or lateral/distributed neuronal organizations
each support different modes of consciousness in different circumstances?
When we are passively engrossed in a film, brain activity
remains posterior, e.g. in Malach’s lateral/distributed scheme. When
we become introspective or engage in command-and-control modes,
frontal cortex kicks in and more global GW/HOT networks take over.
Very localized activity could also result in consciousness (e.g. Zeki’s
famous colour consciousness in isolated V4 activity, or Damasio’s or
Panksepp’s emotional core suggestions).

So the question becomes not so much where, but precisely what
type of neural activity distinguishes consciousness from unconscious
processes. The evidence points to synchronized dendritic LFPs rather
than axonal spikes. And if Block and Kouider are correct, neural
activities supporting unconscious processes must be further divided
into (at least) two sub-types: non-conscious and pre-conscious/
access. There’s plenty of need for lower level subtlety.

A Neural Signature of Self-Control

From Brass and Haggard, in a recent issue of the Journal of Neuroscience (PDF here):

Voluntary action is fundamental to human existence. Recent research suggests that volition involves a specific network of brain activity, centered on the fronto-median cortex. An important but neglected aspect of intentional action involves the decision whether to act or not. This decision process is crucial in daily life because it allows us to form intentions without necessarily implementing them. In the present study, we investigate the neural correlates of intentionally inhibiting actions using functional magnetic resonance imaging. Our data show that a specific area of the fronto-median cortex is more strongly activated when people prepare manual actions but then intentionally cancel them, compared with when they prepare and then complete the same actions. Our results suggest that the human brain network for intentional action includes a control structure for self-initiated inhibition or withholding of intended actions. The mental control of action has an enduring scientific interest, linked to the philosophical concept of "free will." Our results identify a candidate brain area that reflects the crucial decision to do or not to do.

Figure: A, Activation in the dFMC for the contrast of inhibition versus action trials. The z-map is thresholded at z > 3.09 (p <>

Nature's revenge - Cicadas crashing the internet

Because any interruption of my internet connection leaves me feeling as if one of my limbs had been severed, I notice small articles like this from the Aug. 30 Nature Magazine. A clip:

A cicada known as the kumazemi is descending on Japan en masse...cutting households off from their Internet. Apparently mistaking fibre-optic cables for withered branches, they have been punching their one-millimetre-diameter ovipositors into the cables and laying eggs. In at least 1,000 cases over the past two years, the cicadas have either severed the cable or opened up a hole, allowing water to seep in. The Osaka-based Nippon Telephone and Telegraph West Corporation has responded by creating new cables that lack the grooves that the cicadas target with their ovipositors ...

Sexual orientation in women - brain correlates

Ponseti et al. suggest that they can observe a brain correlate of prenatal androgenization in homosexual women - they have less grey matter in their perirhinal cortex than heterosexual women. The article starts with a useful review of the controversial literature on previously suggested brain differences between homosexual and heterosexual individuals of the same sex. Here is their abstract and two figures:

Is sexual orientation associated with structural differences in the brain? To address this question, 80 homosexual and heterosexual men and women (16 homosexual men and 15 homosexual women) underwent structural MRI. We used voxel-based morphometry to test for differences in grey matter concentration associated with gender and sexual orientation. Compared with heterosexual women, homosexual women displayed less grey matter bilaterally in the temporo-basal cortex, ventral cerebellum, and left ventral premotor cortex. The relative decrease in grey matter was most prominent in the left perirhinal cortex. The left perirhinal area also showed less grey matter in heterosexual men than in heterosexual women. Thus, in homosexual women, the perirhinal cortex grey matter displayed a more male-like structural pattern. This is in accordance with previous research that revealed signs of sex-atypical prenatal androgenization in homosexual women, but not in homosexual men. The relevance of the perirhinal area for high order multimodal (olfactory and visual) object, social, and sexual processing is discussed.

Figure 1. Areas of increased GM concentration in heterosexual women compared to homosexual women. Coronal sections from y = 8 to y = −6 (p<0.05;>homosexual) was implicit masked with the contrast heterosexual (women>men). That way the intersection of significant voxels of both contrasts was gathered. As a result we found one cluster that matches both comparisons. That is, this brain area showed both, a lower GM concentration in heterosexual men compared to heterosexual women and a lower GM concentration in homosexual women relative to heterosexual women.

Figure 2. Heterosexual men and homosexual women compared to heterosexual women.
Areas of decreased GM concentration in heterosexual men are shown in blue and areas of decreased GM concentration in homosexual women are shown in yellow. Reduced GM concentration of homosexual women (relative to heterosexual women) is located within a sex dimorphic brain area.

A mouse model for OCD?

An interesting article from Welch et. al. reports finding a mutation that causes mice to display obsessive-compulsive behaviors. From the review of this work by Hyman:

Roughly 2% of humans suffer from obsessive compulsive disorder, but a lack of animal models has impeded research into this condition. Could a genetically engineered mouse model provide an exciting lead?

The mice studied by Welch et al. showed excessive grooming, which resulted in hair loss and skin injuries, as well as anxiety-like traits. These mice lack the gene encoding SAPAP3 — a scaffolding protein that is found in excitatory, glutamate-responsive synapses and is highly expressed only in the striatum region of the brain. The behavioural abnormalities in these mice were reversed by local expression of Sapap3 in the striatal region, which indicates that loss of this gene is responsible for the observed behavioural abnormalities.

The authors also found that a drug from the SSRI class — which selectively enhance serotonin-mediated neurotransmission throughout the brain — that is used to treat OCD in humans decreases both grooming and anxiety in these mice. This is interesting because a condition responsive to an enhancer of serotonin neurotransmission does not signify a primary defect in serotonin-mediated signalling; instead, the defect is in glutamate-responsive synapses. So alterations in serotonin seem to modulate glutamate action. These findings are also noteworthy because Welsh and colleagues have generated a possible mouse model of OCD. Moreover, these observations add to the accumulating, if circumstantial, evidence that OCD and its associated disorders result from abnormalities in neural circuits spanning the frontal, striatal and thalamic regions of the brain.

And, a word of caution:

Even if we can gain assurance with additional research that the behaviours observed in Sapap3-deficient mice reflect abnormalities in circuits that produce human symptoms, we cannot assume that OCD-related conditions in humans involve variations in this gene. These disorders, like other major psychiatric diseases, seem to be heterogeneous with complex underpinnings — probably involving several genes — that, in interaction with developmental and environmental factors, could lead to abnormalities in frontal–striatal–thalamic circuits.

An enzyme that keeps old memories alive

Greg Miller writes a brief review of work by Shema et al. :

Many substances interfere with memory, as any hung-over partygoer can attest. But although booze and drugs can disrupt the making of new memories (such as the embarrassing antics at last night's party), they leave older memories intact. Neuroscientists think this is because, after a time, memories become wired into the brain in a way that makes them harder to wipe out: Long-term memories, in the generally accepted view, are maintained by structural changes to the synaptic connections between neurons.

The study [by Shama et al.] adds to other recent evidence that may challenge, or at least complicate, this view. A team of neuroscientists reports that injecting a drug that blocks an enzyme called protein kinase Mzeta (PKMzeta) into the cerebral cortex of rats makes the animals forget a meal that made them sick weeks earlier. The findings suggest that the continuing activity of PKMzeta is somehow necessary to maintain long-term memory, something that's not predicted by most current hypotheses on the mechanisms of memory. The work also hints at the possibility of future drugs that could tinker with memory--for therapeutic uses or for boosting brainpower.

"This is a somewhat mind-blowing conclusion," says David Glanzman, a neuroscientist at the University of California, Los Angeles. Enzymes similar to PKMzeta are known to be important in early stages of memory formation, Glanzman says, but most researchers had thought that these compounds were not needed to sustain memory once synaptic changes--such as the growth of new synapses or the strengthening of existing ones--had occurred.

...Going forward, it will be important to figure out how specific ZIP's memory-erasing effects are, says Lynn Nadel, a neuroscientist at the University of Arizona in Tucson. "It's possible that ZIP erases all learning, no matter how old," Nadel says. But if the drug works more selectively, it could one day have clinical applications, he says. For example, researchers and clinicians have been looking for compounds capable of eliminating the painful memories of trauma survivors (Science, 2 April 2004, p. 34). The flip side is cognitive enhancement, adds Richard Morris, a neuroscientist at the University of Edinburgh, U.K. "The next step might be to find out whether augmenting the action of PKMzeta can help sustain memories for longer than occurs normally."

Pruning of nerve connections during development.

As we grow from infancy to adulthood, specific connections (synapses) between nerve cells are formed, and excess connections pruned away. Approximately 40% of the connections (synapses) between nerve cells in our brains disappear during development. How does a nerve cell decide which synapses to destroy? Din et al., studying the nematode Caenorhabditis elegans provide evidence that the creation of adult synapses triggers the destruction of developmentally transient synapses forged by the same neuron. David Miller offers a summary figure in his review showing the molecular details of how a primary synapse region matures while a secondary synapse region is eliminated.


Disconnections (Click to enlarge). (Top) The developing HSNL motor neuron initially forms synapses with vulval muscles and motor neurons in two locations. (Bottom) The protein SYG-1 blocks proteolysis of synaptic proteins at primary synapses but allows destruction of secondary synapses. E2, E2 ubiquitin conjugating enzyme; RBX, Ring finger protein.