Chimpanzees and bonobos exhibit divergent spatial memory development.

Spatial cognition and memory are critical cognitive skills underlying foraging behaviors for all primates. While the emergence of these skills has been the focus of much research on human children, little is known about ontogenetic patterns shaping spatial cognition in other species. Comparative developmental studies of nonhuman apes can illuminate which aspects of human spatial development are shared with other primates, versus which aspects are unique to our lineage. Here we present three studies examining spatial memory development in our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (P. paniscus). We first compared memory in a naturalistic foraging task where apes had to recall the location of resources hidden in a large outdoor enclosure with a variety of landmarks (Studies 1 and 2). We then compared older apes using a matched memory choice paradigm (Study 3). We found that chimpanzees exhibited more accurate spatial memory than bonobos across contexts, supporting predictions from these species' different feeding ecologies. Furthermore, chimpanzees - but not bonobos - showed developmental improvements in spatial memory, indicating that bonobos exhibit cognitive paedomorphism (delays in developmental timing) in their spatial abilities relative to chimpanzees. Together, these results indicate that the development of spatial memory may differ even between closely related species. Moreover, changes in the spatial domain can emerge during nonhuman ape ontogeny, much like some changes seen in human children.

Functional neuroimaging of autobiographical memory.

Functional neuroimaging studies of autobiographical memory have grown dramatically in recent years. These studies are important because they can investigate the neural correlates of processes that are difficult to study using laboratory stimuli, including: (i) complex constructive processes, (ii) recollective qualities of emotion and vividness, and (iii) remote memory retrieval. Constructing autobiographical memories involves search, monitoring and self-referential processes that are associated with activity in separable prefrontal regions. The contributions of emotion and vividness have been linked to the amygdala and visual cortex respectively. Finally, there is evidence that recent and remote autobiographical memories might activate the hippocampus equally, which has implications for memory-consolidation theories. The rapid development of innovative methods for eliciting personal memories in the scanner provides the opportunity to delve into the functional neuroanatomy of our personal past.

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.

A Brief Chronicle of CD4 as a Biomarker for HIV/AIDS: A Tribute to the Memory of John L. Fahey.

Foundational cellular immunology research of the 1960s and 1970s, together with the advent of monoclonal antibodies and flow cytometry, provided the knowledge base and the technological capability that enabled the elucidation of the role of CD4 T cells in HIV infection. Research identifying the sources and magnitude of variation in CD4 measurements, standardized reagents and protocols, and the development of clinical flow cytometers all contributed to the feasibility of widespread CD4 testing. Cohort studies and clinical trials provided the context for establishing the utility of CD4 for prognosis in HIV-infected persons, initial assessment of in vivo antiretroviral drug activity, and as a surrogate marker for clinical outcome in antiretroviral therapeutic trials. Even with sensitive HIV viral load measurement, CD4 cell counting is still utilized in determining antiretroviral therapy eligibility and time to initiate therapy. New point of care technologies are helping both to lower the cost of CD4 testing and enable its use in HIV test and treat programs around the world.