Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.

Angelman syndrome (AS) is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG) abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11-q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11-q13. Using a chromosomal engineering strategy, we generated mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m-/p+) were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m-/p+), but not paternal (m+/p-), deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal communication behaviors in human AS patients. Thus, mutant mice with a maternal deletion from Ube3a to Gabrb3 provide an AS mouse model that is molecularly more similar to the contiguous gene deletion form of AS in humans than mice with Ube3a mutation alone. These mice will be valuable for future comparative studies to mice with maternal deficiency of Ube3a alone.

At 6-9 months, human infants know the meanings of many common nouns.

It is widely accepted that infants begin learning their native language not by learning words, but by discovering features of the speech signal: consonants, vowels, and combinations of these sounds. Learning to understand words, as opposed to just perceiving their sounds, is said to come later, between 9 and 15 mo of age, when infants develop a capacity for interpreting others' goals and intentions. Here, we demonstrate that this consensus about the developmental sequence of human language learning is flawed: in fact, infants already know the meanings of several common words from the age of 6 mo onward. We presented 6- to 9-mo-old infants with sets of pictures to view while their parent named a picture in each set. Over this entire age range, infants directed their gaze to the named pictures, indicating their understanding of spoken words. Because the words were not trained in the laboratory, the results show that even young infants learn ordinary words through daily experience with language. This surprising accomplishment indicates that, contrary to prevailing beliefs, either infants can already grasp the referential intentions of adults at 6 mo or infants can learn words before this ability emerges. The precocious discovery of word meanings suggests a perspective in which learning vocabulary and learning the sound structure of spoken language go hand in hand as language acquisition begins.

The acquisition of abstract words by young infants.

Young infants' learning of words for abstract concepts like 'all gone' and 'eat,' in contrast to their learning of more concrete words like 'apple' and 'shoe,' may follow a relatively protracted developmental course. We examined whether infants know such abstract words. Parents named one of two events shown in side-by-side videos while their 6-16-month-old infants (n=98) watched. On average, infants successfully looked at the named video by 10 months, but not earlier, and infants' looking at the named referent increased robustly at around 14 months. Six-month-olds already understand concrete words in this task (Bergelson & Swingley, 2012). A video-corpus analysis of unscripted mother-infant interaction showed that mothers used the tested abstract words less often in the presence of their referent events than they used concrete words in the presence of their referent objects. We suggest that referential uncertainty in abstract words' teaching conditions may explain the later acquisition of abstract than concrete words, and we discuss the possible role of changes in social-cognitive abilities over the 6-14 month period.

Development of hemispheric specialization for lexical pitch-accent in Japanese infants.

Infants' speech perception abilities change through the first year of life, from broad sensitivity to a wide range of speech contrasts to becoming more finely attuned to their native language. What remains unclear, however, is how this perceptual change relates to brain responses to native language contrasts in terms of the functional specialization of the left and right hemispheres. Here, to elucidate the developmental changes in functional lateralization accompanying this perceptual change, we conducted two experiments on Japanese infants using Japanese lexical pitch-accent, which changes word meanings with the pitch pattern within words. In the first behavioral experiment, using visual habituation, we confirmed that infants at both 4 and 10 months have sensitivities to the lexical pitch-accent pattern change embedded in disyllabic words. In the second experiment, near-infrared spectroscopy was used to measure cortical hemodynamic responses in the left and right hemispheres to the same lexical pitch-accent pattern changes and their pure tone counterparts. We found that brain responses to the pitch change within words differed between 4- and 10-month-old infants in terms of functional lateralization: Left hemisphere dominance for the perception of the pitch change embedded in words was seen only in the 10-month-olds. These results suggest that the perceptual change in Japanese lexical pitch-accent may be related to a shift in functional lateralization from bilateral to left hemisphere dominance.