Early Scents Really Do Get 'Etched' In The Brain

Common experience tells us that particular scents of childhood can leave quite an impression, for better or for worse. Now, researchers reporting the results of a brain imaging study online on November 5th in Current Biology, a Cell Press publication, show that first scents really do enjoy a "privileged" status in the brain."We found that the first pairing or association between an object and a smell had a distinct signature in the brain," even in adults, said Yaara Yeshurun of the Weizmann Institute of Science in Israel. "This 'etching' of initial odor memories in the brain was equal for good and bad smells, yet was unique to odor." Sounds did not have the same effect, the research showed.

In the study, the researchers presented adults with a visual object together with one, and later with a second, set of pleasant and unpleasant odors and sounds while their brains were imaged by functional magnetic resonance imaging (fMRI). A week later, the researchers presented the same objects inside the fMRI and tested participants' associations of those images with the scents and smells.

The researchers found that people remembered early associations more clearly when they were unpleasant, regardless of whether they were smelled or heard. The images, however, revealed a unique activation in particular brain regions in the case of their first olfactory (but not auditory) associations. That signature held regardless of whether the odors or sounds were pleasant or unpleasant. The researchers even found that they could predict what a person would remember later based on the activity in their brains on day 1.

Yeshurun explained that it makes good sense to remember unpleasant memories as a kind of evolutionary "risk management." But the findings show that there is also something particularly special about early memories of smells.

That wasn't really unexpected, Yeshurun said -- it is after all a phenomenon that has long fascinated authors, poets, and scientists alike. Still, the results did hold some surprises.

"We expected a unique representation of initial or 'first' olfactory associations but did not expect that it would materialize even in cases where the behavioral evidence did not indicate a stronger memory," Yeshurun said. "In our paradigm, initial and later olfactory associations were remembered equally well, but only first associations had the unique brain representation."

In terms of understanding the brain, the findings suggest that activity in two brain regions, known as the hippocampus and amygdala, together can render a memory "special."

Although any application of the findings would be far off, Yeshurun said the results could suggest ways to strengthen particular memories. "Perhaps more importantly, it may help us generate methods to better forget early and powerful memories, such as trauma," she said.

The researchers include Yaara Yeshurun, Hadas Lapid, Yadin Dudai, and Noam Sobel, of the Weizmann Institute of Science, in Rehovot, Israel.

Babies' Language Learning Starts From The Womb

From their very first days, newborns' cries already bear the mark of the language their parents speak, reveals a new study published online on November 5th in Current Biology, a Cell Press publication. The findings suggest that infants begin picking up elements of what will be their first language in the womb, and certainly long before their first babble or coo."The dramatic finding of this study is that not only are human neonates capable of producing different cry melodies, but they prefer to produce those melody patterns that are typical for the ambient language they have heard during their fetal life, within the last trimester of gestation," said Kathleen Wermke of the University of Würzburg in Germany. "Contrary to orthodox interpretations, these data support the importance of human infants' crying for seeding language development."

Human fetuses are able to memorize sounds from the external world by the last trimester of pregnancy, with a particular sensitivity to melody contour in both music and language, earlier studies showed. Newborns prefer their mother's voice over other voices and perceive the emotional content of messages conveyed via intonation contours in maternal speech (a.k.a. "motherese"). Their perceptual preference for the surrounding language and their ability to distinguish between different languages and pitch changes are based primarily on melody.

Although prenatal exposure to native language was known to influence newborns' perception, scientists had thought that the surrounding language affected sound production much later, the researchers said. It now appears that isn't so.

Wermke's team recorded and analyzed the cries of 60 healthy newborns, 30 born into French-speaking families and 30 born into German-speaking families, when they were three to five days old. That analysis revealed clear differences in the shape of the newborns' cry melodies, based on their mother tongue.

Specifically, French newborns tend to cry with a rising melody contour, whereas German newborns seem to prefer a falling melody contour in their crying. Those patterns are consistent with characteristic differences between the two languages, Wermke said.

The new data show an extremely early impact of native language, the researchers say. Earlier studies of vocal imitation had shown that infants can match vowel sounds presented to them by adult speakers, but only from 12 weeks on. That skill depends on vocal control that just isn't physically possible much earlier, the researchers explain.

"Imitation of melody contour, in contrast, is merely predicated upon well-coordinated respiratory-laryngeal mechanisms and is not constrained by articulatory immaturity," they write. "Newborns are probably highly motivated to imitate their mother's behavior in order to attract her and hence to foster bonding. Because melody contour may be the only aspect of their mother's speech that newborns are able to imitate, this might explain why we found melody contour imitation at that early age."

The researchers include Birgit Mampe, University of Wurzburg, Wurzburg, Germany; Angela D. Friederici, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Anne Christophe, Ecole Normale Superieure/CNRS, Paris, France; and Kathleen Wermke, University of Wurzburg, Wurzburg, Germany.

'Moonlighting' Molecules Discovered; Researchers Uncover New Kink In Gene Control

Since the completion of the human genome sequence, a question has baffled researchers studying gene control: How is it that humans, being far more complex than the lowly yeast, do not proportionally contain in our genome significantly more gene-control proteins?Now, a collaborative effort at the Johns Hopkins School of Medicine to examine protein-DNA interactions across the whole genome has uncovered more than 300 proteins that appear to control genes, a newly discovered function for all of these proteins previously known to play other roles in cells. The results, which appear in the October 30 issue of Cell, provide a partial explanation for human complexity over yeast but also throw a curve ball in what we previously understood about protein functions.

"Everyone knows that transcription factors bind to DNA and everyone knows that they bind in a sequence-specific manner," says Heng Zhu, Ph.D., an assistant professor in pharmacology and molecular sciences and a member of the High Throughput Biology Center. "But you only find what you look for, so we looked beyond and discovered proteins that essentially moonlight as transcription factors."

The team suspects that many more proteins encoded by the human genome might also be moonlighting to control genes, which brings researchers to the paradox that less complex organisms, such as plants, appear to have more transcription factors than humans. "Maybe most of our genes are doing double, triple or quadruple the work," says Zhu. "This may be a widespread phenomenon in humans and the key to how we can be so complex without significantly more genes than organisms like plants."

The team set out to figure out which proteins encoded by the genome bind to which DNA sequences. It had been predicted by examining the human genome sequence that about 1,400 to 1,700 of encoded proteins are so-called transcription factors -- proteins that bind to specific sequences in DNA to turn a gene on or off. The researchers also included in their study, in addition to these proteins, other types that are known to maintain chromosome structure and bind to structurally different RNA. Also included were proteins that normally relay information within a cell and are not thought to directly come in contact with DNA. In total, they collected nearly 4,200 human proteins together on a protein microarray, or protein "chip."

To identify proteins on that chip that bound DNA directly, the group first reviewed previously published scientific literature and catalogued 460 different, short sequences of DNA that are known or predicted to bind proteins.

One at a time, the team tested each of the 460 DNA sequences against the 4,200 protein-containing chip. In addition to finding many protein-DNA interactions for transcription factors, some confirming previously known interactions, the team found 367 new unconventional DNA binding proteins -- proteins known to do other cellular jobs.

"This nearly doubled the number of known protein-DNA interactions," says Jiang Qian, Ph.D., an assistant professor of ophthalmology at Hopkins. "But we only looked at about a fifth of all the proteins in the human genome -- there could be hundreds, even thousands more of these unconventional transcription factors that we don't yet know about."

One of the unconventional transcription factors discovered was the protein MAP Kinase 1, also known as ERK2, a protein long studied for its ability to control cell growth and development via its ability to add phosphate groups to other molecules.

"It's one of the best studied proteins out there, but no one ever thought ERK2 could directly regulate gene expression by actually binding to DNA," says Seth Blackshaw, Ph.D., an assistant professor of neuroscience and a member of the High Throughput Biology Center and the Neuroregeneration Program at the Institute for Cell Engineering.

To be certain that ERK2 really does bind DNA and control genes in living cells, the team tested the protein in human cells. They found that ERK2 mutated to no longer bind DNA causes specific genes to be turned on, while both normal ERK2 and ERK2 that's no longer able to chemically modify proteins turn off those same genes. "It clearly acts to repress specific genes," says Blackshaw. "Maybe this will help clear up some of the puzzles that have arisen in ERK2 experiments over the years."

A central question in understanding how genes are controlled is hich of the 20,000 proteins encoded by our genome act on which segments of DNA. "It's not possible to predict this a priori," Blackshaw says. "Someone has to do the experiment -- because we just don't know enough about how proteins bind to DNA -- patterns have surfaced in this field's 45 year history, but not enough yet to establish any rules."

This study was funded by the National Institutes of Health, a National Eye Institute Vision Core grant, a W. M. Keck Foundation Distinguished Young Investigator in Medical Research Award, a grant from the Ruth and Milton Steinbach Fund and a generous gift from Mr. and Mrs. Robert and Clarice Smith

Authors on the paper are Shaohui Hu, Zhi Xie, Akishi Onishi, Xueping Yu, Lizhi Jiang, Jimmy Lin, Hee-Sool Rho, Crystal Woodard, Hong Wang, Jun-Seop Jeong, Shunyou Long, Xiaofei He, Herschel Wade, Blackshaw, Qian, and Zhu, all of Johns Hopkins.