The very special episode of Family Ties that guest starred Tom Hanks as Alex Keaton’s cough syrup-guzzling, alcoholic uncle scarred me for life. Tom Hanks will be happy to know that he has finally been outdone. News reports circulated this week that people are ingesting hand sanitizers to get drunk. Hand sanitizers contain nearly twice the amount of alcohol as vodka and are toxic because they contain isopropanol, not ethanol. So, hand sanitizers make poor beverages.

Perhaps those in search of a quick high should instead open their wallets and inhale. According to Science Daily, 100% of Euro notes tested near Dublin contained traces of cocaine. Approximately 62% of the Euro notes contained in excess of 2 and 5% contained more than 200 nanograms per note, suggesting these bills might have been used during drug inhalation or transactions. Relative to 5 and 10 Euro notes, 20 and 50 Euro notes tended to have more cocaine residue. Previous studies in the U. S. showed that 65% of dollar bills held traces of cocaine. Researchers believe that cocaine adsorbs to bank notes and rubs off on other bills. Are most people, let alone bankers, therefore sensitized to small amounts of cocaine?

How about LSD? Hallucinogens, like LSD, act at 5-HT2a receptors, as do non-hallucinogens, including lisuride, which is used to treat Parkinson disease. How do 5-HT2a receptors differentially respond to different types of ligand? Gonzalez-Maeso et al. report that hallucinogens activate different cell signaling pathways than do non-hallucinogens in an article published yesterday in Neuron. Both LSD and lisuride act at 5-HT2a receptors to activate phospholipase C-beta via Gq/11 proteins. The authors showed that LSD, but not lisuride, increased the expression of the early growth response-2 (egr-2) gene. A phospholipase C-beta inhibitor, a Src inhibitor and pertussis toxin all blocked LSD-induced increases in egr-2. Therefore, the authors concluded that unlike non-hallucinogens, LSD acts at 5-HT2a receptors to activate pertussis toxin-sensitive Gi/o proteins and Src, which may mediate its hallucinogenic effects.

Nicorette be damned! Quitting smoking is easy…if you’ve had a stroke. Naqvi et al. report that stroke-induced damage to the insula associates with smoking cessation in today’s issue of Science.

The insula lies in the pocket separating the temporal lobe from the parietal lobe and is thought to provide emotional context for sensory information. Sixteen of nineteen smokers who suffered strokes that affected the insula quit smoking immediately. Smokers who sustained damage to the insula were more likely to quit than smokers who had sustained damage to other brain regions. Although several of the patients with insular damage also sustained damage to the putamen, which is part of the striatum thought to be involved in learning drug use behaviors, no other brain region associated with smoking cessation in the stroke patients.

Do smokers with insular damage lose pleasure in smoking? After smoking cessation, none of the patients with insular damage reported losing pleasure in eating or drinking, suggesting that they had not lost motivation or the ability to experience pleasure. Do these patients lose other habits? Unfortunately, the authors did not address this possibility.

These findings suggest that the insula is important in experiencing the need to smoke and is therefore a target for smoking cessation therapy. Considering the insula’s proximity to language centers, surgical lesion of the insula is certainly not advisable. However, targeted pharmacological therapy might some day help smokers quit. According to the authors, the efficacy of smoking cessation programs might be determined by imaging insular activation.

Despite my best efforts to stop it, my most productive planning always occurs in the last five minutes of a yoga class. Relax my mind? I don’t think so! What goes on in the brain when we let our minds wander? Mason et al. report that a network of brain structures is active during daydreaming in a recent article in Science.

The authors had people do repetitive (i. e. boring) tasks, like memorizing and rehearsing the same short list of words forward and backward, for 30 minutes each day. The subjects reported that their minds wandered more during this task than when they were given a new task to do. On the fifth day, the subjects did the same task in an MRI machine. The authors identified regions of the brain that were active during this literally mind-numbing activity relative to those that were active when participants worked on a novel task. Then they correlated the activity of these brain regions to the participants’ daydream frequencies. BOLD signal in the medial prefrontal cortex, cingulate, precuneus, right superior frontal gyrus and the left and right insula associated with daydreaming. In addition to daydreaming, the authors believe that these brain regions might be important in ‘housekeeping’ functions or might cause people to be aware of their daydreams.

Why do we daydream? I’ll look that up once I stop thinking about a beach vacation…

Several sources, including news@nature and the Washington Post, reported today that relative to the early 1990s, the average blood level of folate in women is declining. Folate deficiency is associated with neural tube defects during fetal development. So women of child-bearing age are encouraged to take folate supplements even if they are not pregnant or actively trying to get pregnant. Incidence of neural tube defects has declined by approximately 25%, presumably because we are all taking folate.

So why are folate levels declining? It’s not clear, but officials from the U. S. Centers for Disease Control and Prevention have several ideas. Obese individuals metabolize folate differently than thin people and may need to consume more folate than their thin counterparts. Because obesity is on the rise, that may explain the decline in average folate levels. Alternatively, diet trends may be to blame. In the U. S., the Food and Drug Administration requires that enriched flour used in cereals and breads be fortified with folic acid. But in 2003, the Atkins diet craze encouraged us all to trade in our Cheerios for steaks. Now diet gurus are encouraging people to eat whole grains, which unlike their processed counterparts, are not supplemented with folic acid.

So, women should consume far more folate. That is, unless you remember this bizarre news item from last spring, reporting that each generation of obese pregnant mice fed folate and other methyl donors had increasingly heavier offspring.

What’s new in neuroscience? A physical scientist asked me this question at a holiday party last week. I’d already been thinking about the highs and lows (but mainly highs) of what I’ve seen in 2006, so I told him about my favorite group of papers to come out in the last few months.

The genes that make us human are expressed in the brain and may be involved in brain development. This is the basic gist of several recent papers that sit on the fence between evolutionary genetics and neuroscience. Pollard et al. (my favorite of the bunch) report that among all genes, the non-coding gene HAR1F has had the most accelerated changes in the human relative to other species. HAR1F is expressed in Cajal-Retzius cells, which are important in cortical development, and is developmentally regulated. Since the cortex is specifically enlarged in humans relative to other species, these data may suggest that HAR1F is important in the evolutionary expansion of the human brain.

Popesco et al. looked for genes with the biggest copy-number expansion in humans relative to other species. They report that humans have more copies of the MGC8902 gene than other species. Humans have approximately 50 copies, whereas chimps and macaques have 10 and 4 copies, respectively. MGC8902 encodes repeats of a protein domain called DUF1220, whose function is unknown. DUF1220 domains are only found in primates. In humans, DUF1220 is found in neurons in the hippocampus, cortex and cerebellum.

Finally, Prabhakar et al. report that non-coding genes with the most human-specific substitutions are disproportionately involved in neural cell adhesion.

Best wishes for a New Year filled with great neuroscience.

During the holiday season, Tyzio et al. give us one more reason to buy mom a really nice present. They report that maternal oxytocin, which induces uterine contractions during labor, protects the newborn brain from hypoxic/ischemic neuronal cell death in a recent article in Science.

GABA is the major inhibitory neurotransmitter in the adult brain, but it is the major excitatory neurotransmitter in the neonatal brain. The intracellular chloride concentration is elevated in neonatal relative to adult neurons at least in part because the transporter that shuttles chloride out of the cell is not yet expressed. Therefore the reversal potential, the membrane potential at which the concentration gradient driving an ion in one direction is balanced by the electrochemical gradient driving it in the other, is positive relative to the resting membrane potential, so the driving force for chloride is out of the cell, resulting in GABA-mediated depolarization. In the adult, the chloride exporter helps keep the intracellular chloride concentration low. The reversal potential for chloride is negative relative to the resting membrane potential, so the driving force for chloride is into the cell, resulting in GABA-mediated hyperpolarization.

In hippocampal slices from neonatal rats, the authors found that the number of neurons excited by GABA and the reversal potential for GABA neurons declined right around the time of birth, but rebounded shortly thereafter. During this period, the driving force for chloride ions changed from positive to negative, suggesting that GABA was inhibitory. Neurons grown in culture don’t experience this brief period of inhibition, so the authors proposed that a maternal factor might be the cause. Oxytocin reduced the number of hippocampal pyramidal cells excited by GABA and their intracellular chloride concentration relative to untreated cells. Pups from pregnant dams treated with an oxytocin receptor antagonist did not show GABA-mediated inhibition around the time of birth, suggesting that oxytocin is necessary for this short-lived effect.

So, why does GABA flip-flop? Birth can cause hypoxic conditions, which can lead to excitotoxic cell death. If the source for neuronal excitation is suddenly inhibitory, then the chances for cell death should decline. In the presence of an oxytocin receptor antagonist, hippocampal neurons from late embryonic rats were more vulnerable to anoxic depolarization relative to control neurons, suggesting that oxytocin is neuroprotective in the neonate.

What does this mean for babies born by Cesarean Section? I would think C-section avoids the anoxic conditions present in the birth canal. However, I wonder whether oxytocin analogs, like Pitocin and Syntocinon, that are used to induce labor affect fetal brain development or conversely offer extended protection for the neonatal brain.

In the next week, the shopping malls will overflow with people making last-minute holiday gift purchases. What should you get your favorite neuroscientist? Here are a few suggestions brought to you by our friend, the internet. The Unemployed Philosophers Guild has a whole page dedicated to Freudiana for that very special psychologist in your life. Among my favorites are Freudian Slippers, the Tickle Me Freud doll and the Freudian Sips mug. You can also get Freud and Jung finger puppets, but unfortunately no Ramon y Cajal. Made with Molecules features necklace pendants and earrings with the molecular structures of neurotransmitters and neuromodulators, including dopamine, serotonin, estrogen and caffeine. However, I am partial to the oxytocin baby onesie that says ‘Cuddle’ next to the molecular structure of oxytocin. MWM also carries a holiday greeting card with the mythical peptide P-E-A-C-E (proline-glutamic acid-alanine-cysteine-glutamic acid) gracing its cover. Finally, for the purist, the Anatomical Chart Company has a good old brain gelatin mold and a baseball cap covered with an anatomically correct illustration of the brain and the words ‘Think, think, think’ under the brim.

Happy shopping!

Older siblings in large families are at risk for household chores and babysitting duties and, according to a recent article in Neurology, several cancers as well. Altieri et al. examined over 13,000 cases of nervous system tumors, including astrocytomas, meningiomas and neuroblastomas, in the Swedish Family-Cancer Database and found that the incidence of brain cancers was twice as high in people with four or more siblings than in only children. In children under the age of 15, having three or more younger siblings increased a child’s risk of having brain cancers by two to four times relative to only children.

As any parent with a child in daycare knows, the more children that play in one room, the more colds and coughs any one child will get. According to the authors, because crowded houses are linked to increased rates of infections, their data suggest that cancers of the nervous system may be caused by viruses. They think that young immune systems may be strengthened by certain infections, while teenage immune systems are more vulnerable, and the younger siblings may re-expose older siblings to the viruses.

There are several interesting alternative theories. Helen Pearson suggests that the latter-born children may be exposed to different factors in the womb than their older siblings that affect immune system function. Paul Graham Fisher told Yahoo! Health News that the data may simply indicate that it is common for Swedish people to have more children after one child has been ill.

Because brain tumors are rare in children (brain tumors strike 3 children out of 100,000), it is unclear what the small increase in incidence in older siblings of large families means, let alone what impact the present study will have. Considering that cervical cancer is caused by human papillomavirus, it is tempting to pursue viral causes for brain tumors and imagine a world in which all children are immunized against possible infection. Perhaps if other cancers were shown to have viral causes, the public would stop focusing on the sexual transmission of human papillomavirus and start focusing on how to protect their children from cancer.

In good news for a change, the U. S. House of Representatives approved a bill allocating $1 billion for research and treatment for Autism Spectrum Disorders. This week, I saw two reports about the role of the amygdala in autism and Rett syndrome, which has aspects of autism. Because the amygdala is involved in emotions and social behaviors, I got to thinking about whether treating the symptom (abnormal social behavior) cures the disease.

In news@nature.com, Narelle Towie reports on a study of amygdala size in people with autism in Archives of General Psychiatry. According to the article, children with autism tend to have enlarged amygdalas. The authors found that adults with autism who most avoided eye contact (a common symptom in autism) had smaller amygdalas than other adults and children with autism. Therefore, the authors concluded that the amygdala may be hyperexcitable in children with autism, which may lead to amygdalar cell death and symptom progression in adults.

Rett syndrome is a neurodevelopmental disorder marked by mental retardation, seizures and ataxia that is associated with mutations in the methyl-CpG-binding protein MeCP2. People with Rett syndrome commonly show dysfunctional social behavior and aspects of autism as well as increased anxiety. In PNAS, McGill et al. report increased anxiety-like behavior and enhanced physiological response to stress in mice hypomorphic for Mecp2, which is a mouse model of Rett syndrome. Relative to wild-type mice, the ‘Rett’ mice had increased expression of corticotropin-releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus, the central nucleus of the amygdala and the bed nucleus of the stria terminalis, where it is thought to regulate stress, fear and anxiety, respectively. Bound MeCP2 recruits histone acetylases and histone and DNA methyltransferases, which inhibit gene expression. So, does MeCP2 normally bind to the CRH gene and restrict its expression? Yes indeed! The authors found MeCP2 bound to CRH promoters in wild-type, but not MeCP2 hypomorph mice. So, the increased anxiety in people with Rett syndrome may be mediated by excess CRH.

Treatment with CRH inhibitors might help people with Rett syndrome feel less anxious. Is it possible that restraining fear and anxiety would alleviate some of the abnormal social behavior in these patients? For that matter, would treatments to restrain amygdalar activity treat the social symptoms of Autism Spectrum Disorders, or would it help block disease progression altogether?

PKC-1 regulates secretion of neuropeptides

The atypical protein kinase C PKC-1 is required for exocytosis of dense-core neuropeptide vesicles in worm motoneurons, but it is not involved in synaptic neurotransmitter vesicle exocytosis.