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.

Dyslexia and the failure to form a perceptual anchor

Reading appears to be primarily a visual task, but it has been proposed that children suffering from dyslexia may actually have in impairment in auditory processing. This study reports that a set of learning-disabled and dyslexic children had trouble with certain sound discrimination tasks, supporting the idea that the root of dyslexia could lie in auditory cognition.

Propagating waves mediate information transfer in the motor cortex

The authors here trained macaques to reach for a target upon command, then recorded field potential oscillations from their premotor and motor cortices. Just before the monkey made its reaching motion, the cue triggered beta waves whose phase and amplitude correlated with reaching direction.

Simple fall-off pattern of correlated neural activity in the developing lateral geniculate nucleus

Multielectrode recordings from the lateral geniculate nucleus of movie-watching young ferrets reveal an activity pattern that does not agree with theoretical predictions.

Dynorphin A activates bradykinin receptors to maintain neuropathic pain

Opioids usually alleviate pain by acting at opiate receptors, but this study now reports that the opioid dynorphin A can also activate bradykinin receptors, thereby contributing to neuropathic pain.