Part I. Experimental Studies: 2. Experiment in psychology 3. Experiments on perceiving III Experiments on imaging 4-8. Experiments on remembering: (a) The method of description (b) The method of repeated reproduction (c) The method of picture writing (d) The method of serial reproduction (e) The method of serial reproduction picture material 9. Perceiving, recognizing, remembering 10. A theory of remembering 11. Images and their functions 12. Meaning Part II. Remembering as a Study in Social Psychology: 13. Social psychology 14. Social psychology and the matter of recall 15. Social psychology and the manner of recall 16. Conventionalism 17. The notion of a collective unconscious 18. The basis of social recall 19. A summary and some conclusions.

Remembering. A Study in Experimental and Social Psychology, Cambridge (University Press) 1964.

Trust pervades human societies. Trust is indispensable in friendship, love, families and organizations, and plays a key role in economic exchange and politics. In the absence of trust among trading partners, market transactions break down. In the absence of trust in a country's institutions and leaders, political legitimacy breaks down. Much recent evidence indicates that trust contributes to economic, political and social success. Little is known, however, about the biological basis of trust among humans. Here we show that intranasal administration of oxytocin, a neuropeptide that plays a key role in social attachment and affiliation in non-human mammals, causes a substantial increase in trust among humans, thereby greatly increasing the benefits from social interactions. We also show that the effect of oxytocin on trust is not due to a general increase in the readiness to bear risks. On the contrary, oxytocin specifically affects an individual's willingness to accept social risks arising through interpersonal interactions. These results concur with animal research suggesting an essential role for oxytocin as a biological basis of prosocial approach behaviour.

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Oxytocin increases trust in humans

The blood-brain barrier (BBB) is formed by the brain capillary endothelium and excludes from the brain ∼100% of large-molecule neurotherapeutics and more than 98% of all small-molecule drugs. Despite the importance of the BBB to the neurotherapeutics mission, the BBB receives insufficient attention in either academic neuroscience or industry programs. The combination of so little effort in developing solutions to the BBB problem, and the minimal BBB transport of the majority of all potential CNS drugs, leads predictably to the present situation in neurotherapeutics, which is that there are few effective treatments for the majority of CNS disorders. This situation can be reversed by an accelerated effort to develop a knowledge base in the fundamental transport properties of the BBB, and the molecular and cellular biology of the brain capillary endothelium. This provides the platform for CNS drug delivery programs, which should be developed in parallel with traditional CNS drug discovery efforts in the molecular neurosciences.

https://link.springer.com/content/pdf/10.1602%2Fneurorx.2.1.3.pdf

The Blood-Brain Barrier: Bottleneck in Brain Drug Development

Over more than a century of research has established the fact that sleep benefits the retention of memory. In this review we aim to comprehensively cover the field of "sleep and memory" research by providing a historical perspective on concepts and a discussion of more recent key findings. Whereas initial theories posed a passive role for sleep enhancing memories by protecting them from interfering stimuli, current theories highlight an active role for sleep in which memories undergo a process of system consolidation during sleep. Whereas older research concentrated on the role of rapid-eye-movement (REM) sleep, recent work has revealed the importance of slow-wave sleep (SWS) for memory consolidation and also enlightened some of the underlying electrophysiological, neurochemical, and genetic mechanisms, as well as developmental aspects in these processes. Specifically, newer findings characterize sleep as a brain state optimizing memory consolidation, in opposition to the waking brain being optimized for encoding of memories. Consolidation originates from reactivation of recently encoded neuronal memory representations, which occur during SWS and transform respective representations for integration into long-term memory. Ensuing REM sleep may stabilize transformed memories. While elaborated with respect to hippocampus-dependent memories, the concept of an active redistribution of memory representations from networks serving as temporary store into long-term stores might hold also for non-hippocampus-dependent memory, and even for nonneuronal, i.e., immunological memories, giving rise to the idea that the offline consolidation of memory during sleep represents a principle of long-term memory formation established in quite different physiological systems.

https://www.zora.uzh.ch/id/eprint/77770/1/physiol_rev_93.pdf

About sleep's role in memory

The emergence of publications on extracellular RNA (exRNA) and extracellular vesicles (EV) has highlighted the potential of these molecules and vehicles as biomarkers of disease and therapeutic targets. These findings have created a paradigm shift, most prominently in the field of oncology, prompting expanded interest in the field and dedication of funds for EV research. At the same time, understanding of EV subtypes, biogenesis, cargo and mechanisms of shuttling remains incomplete. The techniques that can be harnessed to address the many gaps in our current knowledge were the subject of a special workshop of the International Society for Extracellular Vesicles (ISEV) in New York City in October 2012. As part of the “ISEV Research Seminar: Analysis and Function of RNA in Extracellular Vesicles (evRNA)”, 6 round-table discussions were held to provide an evidence-based framework for isolation and analysis of EV, purification and analysis of associated RNA molecules, and molecular engineering of EV for therapeutic intervention. This article arises from the discussion of EV isolation and analysis at that meeting. The conclusions of the round table are supplemented with a review of published materials and our experience. Controversies and outstanding questions are identified that may inform future research and funding priorities. While we emphasize the need for standardization of specimen handling, appropriate normative controls, and isolation and analysis techniques to facilitate comparison of results, we also recognize that continual development and evaluation of techniques will be necessary as new knowledge is amassed. On many points, consensus has not yet been achieved and must be built through the reporting of well-controlled experiments. Keywords: extracellular vesicle; exosome; microvesicle; standardization; isolation (Published: 27 May 2013) Citation: Journal of Extracellular Vesicles 2013, 2 : 20360 - http://dx.doi.org/10.3402/jev.v2i0.20360

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Standardization of sample collection, isolation and analysis methods in extracellular vesicle research

Neuropeptides act as neuronal messengers in the brain, influencing many neurobehavioral functions1. Their experimental and therapeutic use in humans has been hampered because, when administered systemically, these compounds do not readily pass the blood–brain barrier, and they evoke potent hormone-like side effects when circulating in the blood2,3. We administered three peptides, melanocortin(4–10) (MSH/ACTH(4–10)), vasopressin and insulin, intranasally and found that they achieved direct access to the cerebrospinal fluid (CSF) within 30 minutes, bypassing the bloodstream.

Sniffing neuropeptides: a transnasal approach to the human brain

Sleep and the circadian system exert a strong regulatory influence on immune functions. Investigations of the normal sleep–wake cycle showed that immune parameters like numbers of undifferentiated naive T cells and the production of pro-inflammatory cytokines exhibit peaks during early nocturnal sleep whereas circulating numbers of immune cells with immediate effector functions, like cytotoxic natural killer cells, as well as anti-inflammatory cytokine activity peak during daytime wakefulness. Although it is difficult to entirely dissect the influence of sleep from that of the circadian rhythm, comparisons of the effects of nocturnal sleep with those of 24-h periods of wakefulness suggest that sleep facilitates the extravasation of T cells and their possible redistribution to lymph nodes. Moreover, such studies revealed a selectively enhancing influence of sleep on cytokines promoting the interaction between antigen presenting cells and T helper cells, like interleukin-12. Sleep on the night after experimental vaccinations against hepatitis A produced a strong and persistent increase in the number of antigen-specific Th cells and antibody titres. Together these findings indicate a specific role of sleep in the formation of immunological memory. This role appears to be associated in particular with the stage of slow wave sleep and the accompanying pro-inflammatory endocrine milieu that is hallmarked by high growth hormone and prolactin levels and low cortisol and catecholamine concentrations.

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Sleep and immune function

Sleep and immunity are bidirectionally linked. Immune system activation alters sleep, and sleep in turn affects the innate and adaptive arm of our body’s defense system. Stimulation of the immune s...

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The Sleep-Immune Crosstalk in Health and Disease

The role of nocturnal sleep for normal immune regulation and its relation to circadian rhythm was examined in 10 men participating in two 51-h sessions One session included two regular wake-sleep cycles; the other included a night of sustained wakefulness followed by a night of recovery sleep Blood was collected every 3 h to determine PBMC counts, including the enumeration of monocytes, NK cells, and lymphocyte subsets (CD19+, CD3+, CD4+, CD8+, HLA-DR+) Production of IL-1beta, TNF-alpha, IL-2, and IFN-gamma was determined after stimulation of whole blood samples with LPS and PHA, respectively Concentrations of IL-6 and cortisol were assessed in plasma Enumeration of cells indicated significant circadian rhythms for all PBMC subsets under conditions of sustained wakefulness Compared with sustained wakefulness, nocturnal sleep acutely reduced the numbers of monocytes, NK cells, and counts of all lymphocyte subsets However, in the afternoon and evening of the day following sleep, counts of NK cells and lymphocytes were significantly higher than after nocturnal wakefulness, indicating that effects of sleep interacted with those of the circadian pacemaker Sleep markedly enhanced production of IL-2 by T cells (CD3+) but did not influence production of IL-1beta and TNF-alpha, or IL-6 concentrations Effects of sleep were not mediated by changes in cortisol The decrease in monocytes, NK cells, and lymphocytes, together with an increased production of IL-2 during sleep, may serve to support ongoing immune defense in extravascular lymphoid tissue during a time of diminished acute Ag challenge

Effects of sleep and circadian rhythm on human circulating immune cells

Many immune parameters show systematic fluctuations over the 24-h day in human blood. Circulating naive T-cells and production of proinflammatory cytokines, like interleukin-12 (IL-12), peak during nighttime, whereas cytotoxic effector leukocytes and production of the anti-inflammatory cytokine IL-10 peak during daytime. These temporal changes originate from a combined influence of the circadian system and sleep. Both brain functions act synergistically and share neuroendocrine effector mechanisms to convey control over immune functions. Sympathetic tone and cortisol levels show a circadian nadir during nighttime and are further suppressed by sleep, whereas growth hormone and prolactin show a circadian peak during nighttime and are further enhanced by sleep. Thus, the circadian system and sleep jointly evoke a unique endocrine constellation that is extremely effective in inducing changes in leukocyte traffic and a shift toward proinflammatory type 1-cytokines during the nocturnal period of sleep, that is, an action with strong clinical implications.

Tanja Lange

Papers

Sniffing neuropeptides: a transnasal approach to the human brain

Sleep and immune function

The Sleep-Immune Crosstalk in Health and Disease

Effects of sleep and circadian rhythm on human circulating immune cells

Effects of sleep and circadian rhythm on the human immune system