Development of automated imaging and analysis for zebrafish chemical screens.

We demonstrate the application of image-based high-content screening (HCS) methodology to identify small molecules that can modulate the FGF/RAS/MAPK pathway in zebrafish embryos. The zebrafish embryo is an ideal system for in vivo high-content chemical screens. The 1-day old embryo is approximately 1mm in diameter and can be easily arrayed into 96-well plates, a standard format for high throughput screening. During the first day of development, embryos are transparent with most of the major organs present, thus enabling visualization of tissue formation during embryogenesis. The complete automation of zebrafish chemical screens is still a challenge, however, particularly in the development of automated image acquisition and analysis. We previously generated a transgenic reporter line that expresses green fluorescent protein (GFP) under the control of FGF activity and demonstrated their utility in chemical screens ¹. To establish methodology for high throughput whole organism screens, we developed a system for automated imaging and analysis of zebrafish embryos at 24-48 hours post fertilization (hpf) in 96-well plates ². In this video we highlight the procedures for arraying transgenic embryos into multiwell plates at 24hpf and the addition of a small molecule (BCI) that hyperactivates FGF signaling ³. The plates are incubated for 6 hours followed by the addition of tricaine to anesthetize larvae prior to automated imaging on a Molecular Devices ImageXpress Ultra laser scanning confocal HCS reader. Images are processed by Definiens Developer software using a Cognition Network Technology algorithm that we developed to detect and quantify expression of GFP in the heads of transgenic embryos. In this example we highlight the ability of the algorithm to measure dose-dependent effects of BCI on GFP reporter gene expression in treated embryos.     

Foraging behaviour in fishes: perspectives on variance

Synopsis The positive relationship between size of prey and frequency of ingestion by predators has been a focal point of investigations in foraging ecology. Field studies compare the frequency distribution of prey sizes in the predator's gut with that in the environment. Laboratory and field (enclosure) studies are based upon comparison of the frequency distributions of prey sizes in controlled environments, before and after the introduction of a predator. Optimal caloric return for foraging effort (i.e. the theory of optimal foraging) has been widely used as a guiding principle in attempts to explain what a fish consumes. There is a body of information, however, which seems to indicate that the perceptual potentialities and cognitive abilities of a predator can account for both the direction of the prey size versus ingestion frequency relationship and the variance surrounding it. Part of this variance may be evidence of systematic ambiguity, a property of cognitive skills causing predators to respond to the same stimulus in different ways and to different stimuli in the same way. More extensive examination of cognitive skills (minimally defined as learning, remembering and forgetting) in fish may permit causal interpretations (immediate and ultimate) of variance in predatory skills. In such a paradigm of foraging behaviour, environmental stimulus is not taken as the predator's object of response (percept); a cognitive representation connects mind to stimulus and this is the criterion for the act of perception. Cognition, here considered as a formal system which acts upon representations, connects mind to response and thus to adaptation. Studies of the relationships among rates of learning, long and short-term memory, rates of forgetting, prey behavior, size and population turnover rates, lateralization of brain functions, diel fluctuations in predator activity levels and sleep, experience, and critical periods in the development of the predator's nervous system should be examined in relation to foraging behaviour.     

短时记忆容量与40Hz脑电事件相关电位分维特性的相关性研究

我们采用不同组块数的汉字词组作为刺激事件,研究了在短时记忆过程中４０Ｈｚ脑电事件相关电位（４０Ｈｚ ＥＲＰｓ）的分维特性。通过短时记忆容量与４０Ｈｚ ＥＲＰｓ分维特性的相关分析,发现在测试组块数在７附近时,４０Ｈｚ ＥＲＰｓ分维数分形维数特性发生了突变,表现为左右半球分维数值相对大小的反转和同一半球内分维数的突降。这与心理学分析得到的汉字短时记忆容量在６、７个组块数附近的结合相吻合。     

Towards the therapeutic use of intranasal neuropeptide administration in metabolic and cognitive disorders

The nose provides an effective way for delivering neuropeptides to the central nervous system, bypassing the blood-brain barrier and avoiding systemic side effects. Thereby intranasal neuropeptide administration enables the modulation of central nervous signaling pathways of body weight regulation and cognitive functions. Central nervous control of energy homeostasis is assumed to rely on hypothalamic neuropeptidergic pathways that are triggered by the peripheral adiposity signals insulin and leptin conveying the amount of body fat to the brain. Melanocortins, including alpha-melanocyte stimulating hormone (alpha-MSH), are essential for inducing anorexigenic/catabolic effects, i.e. for inhibiting caloric intake and increasing energy expenditure. Insulin, in addition to its function as an adiposity signal, also influences memory formation. Here we present a series of studies on the intranasal administration of MSH/ACTH(4-10), a melanocortin receptor agonist, and of insulin. Prolonged administration of MSH/ACTH(4-10) induced weight loss in normal-weight, but not in overweight humans. Intranasal insulin reduced body fat and improved memory functions in the absence of adverse peripheral side effects. Our results may contribute to the future development of therapeutic strategies in disorders like obesity and cognitive impairments that derive from dysfunctions of central nervous neuropeptidergic pathways.     

The trait of human language: lessons from the canal boat children of England

To fully understand human language, an evolved trait that develops in the young without formal instruction, it must be possible to observe language that has not been influenced by instruction. But in modern societies, much of the language that is used, and most of the language that is measured, is confounded by literacy and academic training. This diverts empirical attention from natural habits of speech, causing theorists to miss critical features of linguistic practice. To dramatize this point, I examine data from a special population––the canal boat children of early twentieth century England––whose language developed without academic influence, but was evaluated using instruments designed primarily for academic use. These data, taken together with related research, suggest that formal instruction can convert language from a purely biological trait that was selected, to a talent that was instructed, while altering the users of language themselves. I then review research indicating that formal instruction can also mask or distort inter-sexual differences in the social applications of language, a significant handicap to evolutionary theorizing. I conclude that if biological theories of language are to succeed, they must explain the spontaneous speaking practices of naturally behaving individuals.

Estradiol treatment and its interaction with the cholinergic system: effects on cognitive function in healthy young women

The steroid hormone estradiol has been shown to modulate cognitive function in both animals and humans, and although the exact mechanisms associated with these effects are unknown, interactions with the cholinergic system have been proposed. We examined the neurocognitive effects of short-term estradiol treatment and its interaction with the cholinergic system using the muscarinic receptor antagonist scopolamine in healthy young women. Thirty-four participants (Mean age ± SD = 22.4 ± 4.4) completed baseline cognitive assessment and then received either 100 μg/day transdermal estradiol or transdermal placebo for 31 days. On days 28 and 31 of treatment, further cognitive assessment was performed pre- and 90 min post-scopolamine (0.4 mg) or placebo (saline) injection, under a randomized double-blind placebo-controlled design. Short-term estradiol treatment significantly enhanced spatial working memory with a trend for improvement in long-term verbal learning and memory. Overall, estradiol treatment did not protect against or attenuate the scopolamine-induced impairments in the cognitive domains assessed. Findings suggest that estrogen has minimal effects on cholinergic-mediated cognitive processes following short-term treatment. Effects of estradiol treatment may be dependent on age, dose of estradiol, integrity of cholinergic innervation and baseline endogenous estrogen levels, which may in part explain the inconsistent findings in the literature.     

Co-evolution of learning complexity and social foraging strategies

Variation in learning abilities within populations suggests that complex learning may not necessarily be more adaptive than simple learning. Yet, the high cost of complex learning cannot fully explain this variation without some understanding of why complex learning is too costly for some individuals but not for others. Here we propose that different social foraging strategies can favor different learning strategies (that learn the environment with high or low resolution), thereby maintaining variable learning abilities within populations. Using a genetic algorithm in an agent-based evolutionary simulation of a social foraging game (the producer-scrounger game) we demonstrate how an association evolves between a strategy based on independent search for food (playing a producer) and a complex (high resolution) learning rule, while a strategy that combines independent search and following others (playing a scrounger) evolves an association with a simple (low resolution) learning rule. The reason for these associations is that for complex learning to have an advantage, a large number of learning steps, normally not achieved by scroungers, are necessary. These results offer a general explanation for persistent variation in cognitive abilities that is based on co-evolution of learning rules and social foraging strategies.     

A model for tool-use traditions in primates: implications for the coevolution of culture and cognition

Inspired by the demonstration that tool-use variants among wild chimpanzees and orangutans qualify as traditions (or cultures), we developed a formal model to predict the incidence of these acquired specializations among wild primates and to examine the evolution of their underlying abilities. We assumed that the acquisition of the skill by an individual in a social unit is crucially controlled by three main factors, namely probability of innovation, probability of socially biased learning, and the prevailing social conditions (sociability, or number of potential experts at close proximity). The model reconfirms the restriction of customary tool use in wild primates to the most intelligent radiation, great apes; the greater incidence of tool use in more sociable populations of orangutans and chimpanzees; and tendencies toward tool manufacture among the most sociable monkeys. However, it also indicates that sociable gregariousness is far more likely to produce the maintenance of invented skills in a population than solitary life, where the mother is the only accessible expert. We therefore used the model to explore the evolution of the three key parameters. The most likely evolutionary scenario is that where complex skills contribute to fitness, sociability and/or the capacity for socially biased learning increase, whereas innovative abilities (i.e., intelligence) follow indirectly. We suggest that the evolution of high intelligence will often be a byproduct of selection on abilities for socially biased learning that are needed to acquire important skills, and hence that high intelligence should be most common in sociable rather than solitary organisms. Evidence for increased sociability during hominin evolution is consistent with this new hypothesis.