Cognition wars

In what kinds of physical systems can cognition be realized? There are currently competing answers among scientists and theorists of cognition. There are many plant scientists who maintain that cognition can be realized in plants. There are biological scientists who maintain that cognition is materially realized in bacteria. In this paper, I will present the basis for such claims and evaluate them and discuss the future for theories of the metaphysical basis of cognition in the cognitive sciences.     

What is a Cognitive Process?

In this commentary to Serrano et al. (2013), I applaud this foundation article for being a breath of fresh air because it addresses the question “What is cognition?” Too often in the cognitive sciences, we leave that question unanswered or worse, unasked. I come not to criticize but to offer a helpful suggestion aimed a pulling together some of the separate strands weaved throughout this article.     

Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells

Our understanding of Alzheimer's disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer's disease, both caused by a duplication of the amyloid-β precursor protein gene (APP; termed APP(Dp)), two with sporadic Alzheimer's disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APP(Dp) patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-β(1-40), phospho-tau(Thr?231) and active glycogen synthase kinase-3β (aGSK-3β). Neurons from APP(Dp) and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with β-secretase inhibitors, but not γ-secretase inhibitors, caused significant reductions in phospho-Tau(Thr?231) and aGSK-3β levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-β, in GSK-3β activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer's disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer's disease, even though it can take decades for overt disease to manifest in patients.     

Patterning organic single-crystal transistor arrays

Field-effect transistors made of organic single crystals are ideal for studying the charge transport characteristics of organic semiconductor materials. Their outstanding device performance, relative to that of transistors made of organic thin films, makes them also attractive candidates for electronic applications such as active matrix displays and sensor arrays. These applications require minimal cross-talk between neighbouring devices. In the case of thin film systems, simple patterning of the active semiconductor layer minimizes cross-talk. But when using organic single crystals, the only approach currently available for creating arrays of separate devices is manual selection and placing of individual crystals-a process prohibitive for producing devices at high density and with reasonable throughput. In contrast, inorganic crystals have been grown in extended arrays, and efficient and large-area fabrication of silicon crystalline islands with high mobilities for electronic applications has been reported. Here we describe a method for effectively fabricating large arrays of single crystals of a wide range of organic semiconductor materials directly onto transistor source-drain electrodes. We find that film domains of octadecyltriethoxysilane microcontact-printed onto either clean Si/SiO(2) surfaces or flexible plastic provide control over the nucleation of vapour-grown organic single crystals. This allows us to fabricate large arrays of high-performance organic single-crystal field-effect transistors with mobilities as high as 2.4 cm(2) V(-1) s(-1) and on/off ratios greater than 10(7), and devices on flexible substrates that retain their performance after significant bending. These results suggest that our fabrication approach constitutes a promising step that might ultimately allow us to utilize high-performance organic single-crystal field-effect transistors for large-area electronics applications.     

NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus

New neurons are continuously integrated into existing neural circuits in adult dentate gyrus of the mammalian brain. Accumulating evidence indicates that these new neurons are involved in learning and memory. A substantial fraction of newly born neurons die before they mature and the survival of new neurons is regulated in an experience-dependent manner, raising the possibility that the selective survival or death of new neurons has a direct role in a process of learning and memory--such as information storage--through the information-specific construction of new circuits. However, a critical assumption of this hypothesis is that the survival or death decision of new neurons is information-specific. Because neurons receive their information primarily through their input synaptic activity, we investigated whether the survival of new neurons is regulated by input activity in a cell-specific manner. Here we developed a retrovirus-mediated, single-cell gene knockout technique in mice and showed that the survival of new neurons is competitively regulated by their own NMDA-type glutamate receptor during a short, critical period soon after neuronal birth. This finding indicates that the survival of new neurons and the resulting formation of new circuits are regulated in an input-dependent, cell-specific manner. Therefore, the circuits formed by new neurons may represent information associated with input activity within a short time window in the critical period. This information-specific addition of new circuits through selective survival or death of new neurons may be a unique attribute of new neurons that enables them to play a critical role in learning and memory.     

A juvenile early hominin skeleton from Dikika, Ethiopia

Understanding changes in ontogenetic development is central to the study of human evolution. With the exception of Neanderthals, the growth patterns of fossil hominins have not been studied comprehensively because the fossil record currently lacks specimens that document both cranial and postcranial development at young ontogenetic stages. Here we describe a well-preserved 3.3-million-year-old juvenile partial skeleton of Australopithecus afarensis discovered in the Dikika research area of Ethiopia. The skull of the approximately three-year-old presumed female shows that most features diagnostic of the species are evident even at this early stage of development. The find includes many previously unknown skeletal elements from the Pliocene hominin record, including a hyoid bone that has a typical African ape morphology. The foot and other evidence from the lower limb provide clear evidence for bipedal locomotion, but the gorilla-like scapula and long and curved manual phalanges raise new questions about the importance of arboreal behaviour in the A. afarensis locomotor repertoire.     

Astroglia induce neurogenesis from adult neural stem cells

During an investigation of the mechanisms through which the local environment controls the fate specification of adult neural stem cells, we discovered that adult astrocytes from hippocampus are capable of regulating neurogenesis by instructing the stem cells to adopt a neuronal fate. This role in fate specification was unexpected because, during development, neurons are generated before most of the astrocytes. Our findings, together with recent reports that astrocytes regulate synapse formation and synaptic transmission, reinforce the emerging view that astrocytes have an active regulatory role--rather than merely supportive roles traditionally assigned to them--in the mature central nervous system.     

Therapeutic approaches to protein-misfolding diseases

Several sporadic and genetic diseases are caused by protein misfolding. These include cystic fibrosis and other devastating diseases of childhood as well as Alzheimer's, Parkinson's and other debilitating maladies of the elderly. A unified view of the molecular and cellular pathogenesis of these conditions has led to the search for chemical chaperones that can slow, arrest or revert disease progression. Molecules are now emerging that link our biophysical insights with our therapeutic aspirations.