Friday, September 21, 2018

Giving Ecstasy to Octopuses

Edsinger and Dölen have found out how to make the normally shy and retiring octopus into a party animal. They found that MDMA (phenethylamine (+/−)-3,4-methylendioxymethamphetamine, also known as Ecstasy) has prosocial effects, just as it does in humans. The indicates that the role of the serotonergic neurotransmission (that MDMA acts on) in regulating social behaviors has been evolutionarily conserved over 500 million years.
Human and octopus lineages are separated by over 500 million years of evolution and show divergent anatomical patterns of brain organization. Despite these differences, growing evidence suggests that ancient neurotransmitter systems are shared across vertebrate and invertebrate species and in many cases enable overlapping functions. Sociality is widespread across the animal kingdom, with numerous examples in both invertebrate (e.g., bees, ants, termites, and shrimps) and vertebrate (e.g., fishes, birds, rodents, and primates) lineages [6]. Serotonin is an evolutionarily ancient molecule that has been implicated in regulating both invertebrate and vertebrate social behaviors, raising the possibility that this neurotransmitter’s prosocial functions may be conserved across evolution. Members of the order Octopoda are predominantly asocial and solitary. Although at this time it is unknown whether serotonergic signaling systems are functionally conserved in octopuses, ethological studies indicate that agonistic behaviors are suspended during mating, suggesting that neural mechanisms subserving social behaviors exist in octopuses but are suppressed outside the reproductive period. Here we provide evidence that, as in humans, the phenethylamine (+/−)-3,4-methylendioxymethamphetamine (MDMA) enhances acute prosocial behaviors in Octopus bimaculoides. This finding is paralleled by the evolutionary conservation of the serotonin transporter (SERT, encoded by the Slc6A4 gene) binding site of MDMA in the O. bimaculoides genome. Taken together, these data provide evidence that the neural mechanisms subserving social behaviors exist in O. bimaculoides and indicate that the role of serotonergic neurotransmission in regulating social behaviors is evolutionarily conserved.

Thursday, September 20, 2018

Building molecular machines.

In an open source PNAS news article, Stephen Ornes describes efforts to build molecular machines modeled on our own biochemical processes - possibly artificial muscles or molecular electronics. It makes a fascinating read. A few clips:
Some of the smallest, most useful machines known to science are the biological molecules that keep living things living. The protein myosin drives the contraction and relaxation of muscle. Kinesin drags cellular cargo around the cell. Motor enzymes unwind, rewind, and maintain DNA, and bacteria use a molecular motor to rotate their whip-like flagella up to 100,000 times per minute, propelling them forward. These machines turn chemical energy into motion. They’re very efficient at their jobs.
The idea of using molecules to build minuscule machines that perform useful tasks dates back at least to a lecture given in 1959 by physicist Richard Feynman titled “There’s Plenty of Room at the Bottom.”* More recently, demonstrations of artificial molecular machines offer good reasons to think that such devices are feasible. Researchers have forged motors, shuttles, elevators, walkers, and pumps out of molecules, and powered them with electrical energy, chemical reactions, or light. Tiny motor by tiny motor, these demonstrations are inching toward future applications that could range from molecular electronics to artificial muscles.
...molecular machines are by nature floppy, like the soft matter that makes up the human body, whereas macroscopic machines are typically made from rigid materials such as metal. But it’s also a consequence of scale. Although the laws of physics don’t change in the nanoworld, their relative influences do. Concepts such as inertia and momentum—critical to the design of machines like cars and planes—become irrelevant. So does gravity, because molecules have such a small mass. Movement at the nanoscale is dominated instead by viscosity and Brownian motion, the random bumbling of individual molecules caused by thermal fluctuations...Katsonis calls this molecular environment a “Brownian storm.” In a 2007 article on the physics of nanoscale machines, physicist R. Dean Astumian at the University of Maine in Orono, ME, likened the challenges to swimming in molasses and walking in a hurricane.
The article gives numerous examples of efforts to develop nanoscale motors driven by electrical energy, chemical energy, or light.

Sunday, September 16, 2018

Mapping our subjective feelings.

Nummenmaa et al.  do a massive job of data gathering whose purpose left me scratching my head on first sight...wondering why such an effort is useful.  But then, if someone asked me how I would describe my subjective experience  I wouldn't know where to start.  In the introduction to their open source article they "use the word feeling to simply refer to the current, subjectively accessible phenomenological state of an individual...Despite the centrality of subjective feelings to ourselves and our conscious well-being, the relative organization and determinants of different feelings have remained poorly understood. "  I pass on their abstract and a summary graphic from the article.

Subjective feelings are a central feature of human life, yet their relative organization has remained elusive. We mapped the “human feeling space” for 100 core feelings ranging from cognitive and affective processes to somatic sensations; in the analysis, we combined basic dimension rating, similarity mapping, bodily sensation mapping, and neuroimaging meta-analysis. All feelings were emotionally loaded, and saliencies of bodily and mental experiences were correlated. Feelings formed five groups: positive emotions, negative emotions, cognitive processes, somatic states, and homeostatic states. Feeling space was best explained by emotionality, mental experience, and bodily sensation topographies. Subjectively felt similarity of feelings was associated with basic feeling dimensions and the bodily sensation maps. This shows that subjective feelings are categorical, emotional, and embodied.
Subjective feelings are a central feature of human life. We defined the organization and determinants of a feeling space involving 100 core feelings that ranged from cognitive and affective processes to somatic sensations and common illnesses. The feeling space was determined by a combination of basic dimension rating, similarity mapping, bodily sensation mapping, and neuroimaging meta-analysis. A total of 1,026 participants took part in online surveys where we assessed (i) for each feeling, the intensity of four hypothesized basic dimensions (mental experience, bodily sensation, emotion, and controllability), (ii) subjectively experienced similarity of the 100 feelings, and (iii) topography of bodily sensations associated with each feeling. Neural similarity between a subset of the feeling states was derived from the NeuroSynth meta-analysis database based on the data from 9,821 brain-imaging studies. All feelings were emotionally valenced and the saliency of bodily sensations correlated with the saliency of mental experiences associated with each feeling. Nonlinear dimensionality reduction revealed five feeling clusters: positive emotions, negative emotions, cognitive processes, somatic states and illnesses, and homeostatic states. Organization of the feeling space was best explained by basic dimensions of emotional valence, mental experiences, and bodily sensations. Subjectively felt similarity of feelings was associated with basic feeling dimensions and the topography of the corresponding bodily sensations. These findings reveal a map of subjective feelings that are categorical, emotional, and embodied.
Here is their two dimensional map of feeling space (click to enlarge, or better, click link to original open source article.)

Thursday, September 13, 2018

Details of how a fear response is unlearned.

Learning requires the formation of new nerve connections. When that learning is extinguished are those connections inhibited or lost? Wan Lai et al. provide evidence for the latter:

Whether learning-induced changes in neuronal circuits are inhibited or erased during the process of unlearning remains unclear. In this study, we examined the impact of auditory-cued fear conditioning and extinction on the remodeling of synaptic connections in the living mouse auditory cortex. We found that fear conditioning leads to cue-specific formation of new postsynaptic dendritic spines, whereas fear extinction preferentially eliminates these new spines in a cue-specific manner. Our findings suggest that learning-related changes of synaptic connections in the cortex are at least partially reversed after unlearning.
Fear conditioning-induced behavioral responses can be extinguished after fear extinction. While fear extinction is generally thought to be a form of new learning, several lines of evidence suggest that neuronal changes associated with fear conditioning could be reversed after fear extinction. To better understand how fear conditioning and extinction modify synaptic circuits, we examined changes of postsynaptic dendritic spines of layer V pyramidal neurons in the mouse auditory cortex over time using transcranial two-photon microscopy. We found that auditory-cued fear conditioning induced the formation of new dendritic spines within 2 days. The survived new spines induced by fear conditioning with one auditory cue were clustered within dendritic branch segments and spatially segregated from new spines induced by fear conditioning with a different auditory cue. Importantly, fear extinction preferentially caused the elimination of newly formed spines induced by fear conditioning in an auditory cue-specific manner. Furthermore, after fear extinction, fear reconditioning induced reformation of new dendritic spines in close proximity to the sites of new spine formation induced by previous fear conditioning. These results show that fear conditioning, extinction, and reconditioning induce cue- and location-specific dendritic spine remodeling in the auditory cortex. They also suggest that changes of synaptic connections induced by fear conditioning are reversed after fear extinction.

Wednesday, September 12, 2018

Exposure to opposing views on social media can increase political polarization.

A sobering study by Bail et al. (open source) shows that just getting us out of our tribes' social media echo chambers does not have the palliative softening effect commonly supposed, but rather increases political polarization:

Social media sites are often blamed for exacerbating political polarization by creating “echo chambers” that prevent people from being exposed to information that contradicts their preexisting beliefs. We conducted a field experiment that offered a large group of Democrats and Republicans financial compensation to follow bots that retweeted messages by elected officials and opinion leaders with opposing political views. Republican participants expressed substantially more conservative views after following a liberal Twitter bot, whereas Democrats’ attitudes became slightly more liberal after following a conservative Twitter bot—although this effect was not statistically significant. Despite several limitations, this study has important implications for the emerging field of computational social science and ongoing efforts to reduce political polarization online.
There is mounting concern that social media sites contribute to political polarization by creating “echo chambers” that insulate people from opposing views about current events. We surveyed a large sample of Democrats and Republicans who visit Twitter at least three times each week about a range of social policy issues. One week later, we randomly assigned respondents to a treatment condition in which they were offered financial incentives to follow a Twitter bot for 1 month that exposed them to messages from those with opposing political ideologies (e.g., elected officials, opinion leaders, media organizations, and nonprofit groups). Respondents were resurveyed at the end of the month to measure the effect of this treatment, and at regular intervals throughout the study period to monitor treatment compliance. We find that Republicans who followed a liberal Twitter bot became substantially more conservative posttreatment. Democrats exhibited slight increases in liberal attitudes after following a conservative Twitter bot, although these effects are not statistically significant. Notwithstanding important limitations of our study, these findings have significant implications for the interdisciplinary literature on political polarization and the emerging field of computational social science.

Tuesday, September 11, 2018

How exercise slows Alzheimer’s disease.

Wow…if I ever needed more encouragement to keep up my exercise routines (mainly swimming, biking, and a few weights) Choi et al. provide it by demonstrating that in a mouse model of Alzheimer's disease, exercise improves memory through a combination of encouraging the generation of new nerve cells in the hippocampus and increasing the levels of brain-derived neurotrophic factor (BDNF) that supports neuronal growth and survival. Their abstract:
Adult hippocampal neurogenesis (AHN) is impaired before the onset of Alzheimer’s disease (AD) pathology. We found that exercise provided cognitive benefit to 5×FAD mice, a mouse model of AD, by inducing AHN and elevating levels of brain-derived neurotrophic factor (BDNF). Neither stimulation of AHN alone, nor exercise, in the absence of increased AHN, ameliorated cognition. We successfully mimicked the beneficial effects of exercise on AD mice by genetically and pharmacologically inducing AHN in combination with elevating BDNF levels. Suppressing AHN later led to worsened cognitive performance and loss of preexisting dentate neurons. Thus, pharmacological mimetics of exercise, enhancing AHN and elevating BDNF levels, may improve cognition in AD. Furthermore, applied at early stages of AD, these mimetics may protect against subsequent neuronal cell death.

Monday, September 10, 2018

Robots R Us

Two recent NYTimes pieces - one by Sherry Turtle (professor in the program in Science, Technology and Society at M.I.T.) and the other by Andy Clark (professor of logic and metaphysics at the University of Edinburgh) - lay out starkly opposing views of the desirability of humans moving toward increased interactions with, and possible enhancements by, robots. You should read both. Turtle sees a potential diminution of our humanity:
The narrative begins with the idea that companionate robots would be “better than nothing,” better because there aren’t enough people to teach, love and tend to people. But that idea quickly shifts into another: robots would be better than most anything. Unlike people, they would not abandon you or get sick and die. They might not be capable of love, but they won’t break your heart. From better than nothing to better than anything. These are stations on our voyage to forgetting what it means to be human. But the forgetting begins long before we have a robot companion in place; it begins when we even think of putting one in place. To build the robots, we must first rebuild ourselves as people ready to be their companions.
Clark looks towards a glorious enhancement of what it means to be human. He begins with a list that includes improving normal mental functioning and generating a wide spectrum of ways of being:
We now glimpse the next steps in human cultural and cognitive evolution, continuing the trend that started with the arrival of human language and the (much later) invention of writing and the external storage and transmission of ideas. The new steps herald an age of fluidity and demand answers to a host of questions…The two most important such questions are simply: How should we negotiate this dauntingly large space of human possibility? And what costs are we willing to tolerate along the way?
The first is a question of practice, the second of ethics. Practically speaking, it will not be easy to decide in a world of so many possible ways of being, so many enhancements and augmentations, and so many social practices, which ones are for us. 
Ethically speaking, we need to ask what new costs and inequalities the freedoms and augmentations of some may mean for others. We need to ask if we are willing to tolerate some inequality as part of the rollout process for a more fluid and interconnected world. Issues of privacy and the right to control (including to trade or sell) our personal information are vividly with us. Not knowing quite where we as protected selves stop and the world around us begins, law and policy struggle to decide if (for example) information stored on our phones is enough like information stored in our heads to warrant the same protections. Law, education and social policy currently lag behind many interacting waves of change. What is up for grabs is what we humans are, and what we will become.