Wearable sensors that detect and quantify biomarkers in retrievable biofluids (e.g., interstitial fluid, sweat, tears) provide information on human dynamic physiological and psychological states. This information can transform health and wellness by providing actionable feedback. Due to outdated and insufficiently sensitive technologies, current on-body sensing systems have capabilities limited to pH, and a few high-concentration electrolytes, metabolites, and nutrients. As such, wearable sensing systems cannot detect key low-concentration biomarkers indicative of stress, inflammation, metabolic, and reproductive status.  We are revolutionizing sensing. Our electronic biosensors detect virtually any signaling molecule or metabolite at ultra-low levels. We have monitored serotonin, dopamine, cortisol, phenylalanine, estradiol, progesterone, and glucose in blood, sweat, interstitial fluid, and tears. The sensors are based on modern nanoscale semiconductor transistors that are straightforwardly scalable for manufacturing. We are developing sensors for >40 biomarkers for personalized continuous monitoring (e.g., smartwatch, wearable patch) that will provide feedback for treating chronic health conditions (e.g., perimenopause, stress disorders, phenylketonuria). Moreover, our sensors will enable female fertility monitoring and the adoption of more healthy lifestyles to prevent disease and improve physical and cognitive performance.

Any sensory experience of the world, from the touch of a caress to the smile on our friend’s face, is embedded in time and it is often associated with the perception of the flow of it. The perception of time is therefore a peculiar sensory experience built without dedicated sensors. How the perception of time and the content of a sensory experience interact to give rise to this unique percept is unclear. A few empirical evidences show the existence of this interaction, for example the speed of a moving object or the number of items displayed on a computer screen can bias the perceived duration of those objects. However, to what extent the coding of time is embedded within the coding of the stimulus itself, is sustained by the activity of the same or distinct neural populations and subserved by similar or distinct neural mechanisms is far from clear. Addressing these puzzles represents a way to gain insight on the mechanism(s) through which the brain represents the passage of time. In my talk I will present behavioral and neuroimaging studies to show how concurrent changes of visual stimulus duration, speed, visual contrast and numerosity, shape and modulate brain’s and pupil’s responses and, in case of numerosity and time, influence the topographic organization of these features along the cortical visual hierarchy.

This course provides a fundamental foundation in the modern techniques of experimental neuroscience. It introduces the essentials of sensors, motor control, microcontrollers, programming, data analysis, and machine learning by guiding students through the “hands on” construction of an increasingly capable robot. In parallel, related concepts in neuroscience are introduced as nature’s solution to the challenges students encounter while designing and building their own intelligent system.

Ali Weber (University of Washington, USA) uses the the hawkmoth as a model system, to investigate how information from a small number of mechanoreceptors on the wings are used in flight control. She employs a combination of experimental and computational techniques to study how these sensors respond during flight and how one might optimally array a set of these sensors to best provide feedback during flight.

Dr. Looger will present updates on a variety of molecular tools for studying & manipulating neural circuits & other preparations. Topics include genetically encoded calcium indicators (including the new ultra-fast jGCaMP8 variants), neurotransmitter sensors (improved versions for following glutamate, GABA, acetylcholine, serotonin), optogenetic effectors including the new “enhanced Magnets” dimerizers, AAV serotypes for retrograde labeling & altered tropism, probes for correlative light-electron microscopy, chemical gene switches, etc. He will make all his slides freely available - so don’t worry about hurriedly taking notes; instead focus on questions and ideas for collaboration. Please bring your suggestions for molecular tools that would be transformative for the field.

Talks and panel discussions around the LifeQ process of moving from the embedded engineering of sensors on edge devices to big health data analysis in the cloud.

I will argue that the circuit architecture of the early olfactory system provides an adaptive, efficient mechanism for compressing the vast space of odor mixtures into the responses of a small number of sensors. In this view, the olfactory sensory repertoire employs a disordered code to compress a high dimensional olfactory space into a low dimensional receptor response space while preserving distance relations between odors. The resulting representation is dynamically adapted to efficiently encode the changing environment of volatile molecules. I will show that this adaptive combinatorial code can be efficiently decoded by systematically eliminating candidate odorants that bind to silent receptors. The resulting algorithm for 'estimation by elimination' can be implemented by a neural network that is remarkably similar to the early olfactory pathway in the brain. Finally, I will discuss how diffuse feedback from the central brain to the bulb, followed by unstructured projections back to the cortex, can produce the convergence and divergence of the cortical representation of odors presented in shared or different contexts. Our theory predicts a relation between the diversity of olfactory receptors and the sparsity of their responses that matches animals from flies to humans. It also predicts specific deficits in olfactory behavior that should result from optogenetic manipulation of the olfactory bulb and cortex, and in some disease states.

A single person can be the source of billions of data points, whether these are generated from everyday internet use, healthcare records, wearable sensors or participation in experimental research. This vast amount of data can be used to make predictions about people and systems: what is the probability this person will develop diabetes in the next year? Will commit a crime? Will be a good employee? Is of a particular ethnicity? Predictions are simply represented by a number, produced by an algorithm. A single number in itself is not biased. How that number was generated, interpreted and subsequently used are all processes deeply susceptible to human bias and prejudices. This session will explore a philosophical perspective of data ethics and discuss practical steps to reducing statistical bias. There will be opportunity in the last section of the session for attendees to discuss and troubleshoot ethical questions from their own analyses in a ‘Data Clinic’.

Coordinated activity across networks of neurons is a hallmark of both resting and active behavioral states in many species, including worms, flies, fish, mice and humans. These global patterns alter energy metabolism in the brain over seconds to hours, making oxygen consumption and glucose uptake widely used proxies of neural activity. However, whether changes in neural activity are causally related to changes in metabolic flux in intact circuits on the sub-second timescales associated with behavior, is unclear. Moreover, it is unclear whether differences between rest and action are associated with spatiotemporally structured changes in neuronal energy metabolism at the subcellular level. My work combines two-photon microscopy across the fruit fly brain with sensors that allow simultaneous measurements of neural activity and metabolic flux, across both resting and active behavioral states. It demonstrates that neural activity drives changes in metabolic flux, creating a tight coupling between these signals that can be measured across large-scale brain networks. Further, using local optogenetic perturbation, I show that even transient increases in neural activity result in rapid and persistent increases in cytosolic ATP, suggesting that neuronal metabolism predictively allocates resources to meet the energy demands of future neural activity. Finally, these studies reveal that the initiation of even minimal behavioral movements causes large-scale changes in the pattern of neural activity and energy metabolism, revealing unexpectedly widespread engagement of the central brain.

Puberty is a brain-driven phenomenon, which is under the control of sophisticated regulatory networks that integrate a large number of endogenous and environmental signals, including metabolic and nutritional cues. Puberty onset is tightly bound to the state of body energy reserves, and deregulation of energy/metabolic homeostasis is often associated with alterations in the timing of puberty. However, despite recent progress in the field, our knowledge of the specific molecular mechanisms and pathways whereby our brain decode metabolic information to modulate puberty onset remains fragmentary and incomplete. Compelling evidence, gathered over the last fifteen years, supports an essential role of hypothalamic neurons producing kisspeptins, encoded by Kiss1, in the neuroendocrine control of puberty. Kiss1 neurons are major components of the hypothalamic GnRH pulse generator, whose full activation is mandatory pubertal onset. Kiss1 neurons seemingly participate in transmitting the regulatory actions of metabolic cues on pubertal maturation. However, the modulatory influence of metabolic signals (e.g., leptin) on Kiss1 neurons might be predominantly indirect and likely involves also the interaction with other transmitters and neuronal populations. In my presentation, I will review herein recent work of our group, using preclinical models, addressing the molecular mechanisms whereby Kiss1 neurons are modulated by metabolic signals, and thereby contribute to the nutritional control of puberty. In this context, the putative roles of the energy/metabolic sensors, AMP-activated protein kinase (AMPK) and SIRT1, in the metabolic control of Kiss1 neurons and puberty will be discussed. In addition, I will summarize recent findings from our team pointing out a role of central de novo ceramide signaling in mediating the impact of obesity of (earlier) puberty onset, via non-canonical, kisspeptin-related pathways. These findings are posed of translational interest, as perturbations of these molecular pathways could contribute to the alterations of pubertal timing linked to conditions of metabolic stress in humans, ranging from malnutrition to obesity, and might become druggable targets for better management of pubertal disorders.

The combination of two-photon microscopy recordings and powerful calcium-dependent fluorescent sensors enables simultaneous recording of unprecedentedly large populations of neurons. While these sensors have matured over several generations of development, computational methods to process their fluorescence are often inefficient and the results hard to interpret. Here we introduce Suite2p: a fast, accurate, parameter-free and complete pipeline that registers raw movies, detects active and/or inactive cells (using Cellpose), extracts their calcium traces and infers their spike times. Suite2p runs faster than real time on standard workstations and outperforms state-of-the-art methods on newly developed ground-truth benchmarks for motion correction and cell detection.

Dr. Stowers obtained her PhD at Harvard University and remained there to undertake the study of olfactory-mediated behavior with Catherine Dulac. During this time she completed experiments identifying vomeronasal organ neurons as sensors for mouse pheromones. In 2002 she began independent work at The Scripps Research Institute where she remains today. Her lab is leveraging the olfactory system to identify and study the information code that underlies emotion-linked innate behavior. She has been a Pew Scholar and a Senior Scholar in Neuroscience from the Ellison Medical Foundation.

During communication, alignment between signals and sensors can be critical. Signals are often best perceived from specific angles, and sensory systems can also exhibit strong directional biases. However, we know little about how animals establish and maintain such signaling alignment during communication. To investigate this, we characterized the spatial dynamics of visual courtship signal- ing in the jumping spider Habronattus pyrrithrix. The male performs forward-facing displays involving complex color and movement patterns, with distinct long- and short-range phases. The female views displays with 2 distinct eye types and can only perceive colors and fine patterns of male displays when they are presented in her frontal field of view. Whether and how courtship interactions pro- duce such alignment between male display and female field of view is unknown. We recorded relative positions and orientations of both actors throughout courtship and established the role of each sex in maintaining signaling alignment. Males always oriented their displays toward the female. However, when females were free to move, male displays were consistently aligned with female princi- pal eyes only during short-range courtship. When female position was fixed, signaling alignment consistently occurred during both phases, suggesting that female movement reduces communication efficacy. When female models were experimentally rotated to face away during courtship, males rarely repositioned themselves to re-align their display. However, males were more likely to present cer- tain display elements after females turned to face them. Thus, although signaling alignment is a function of both sexes, males appear to rely on female behavior for effective communication

My lab seeks to understand how the mammalian brain performs the computations that underlie cognitive functions, including decision-making, short-term memory, and spatial navigation, at the level of the building blocks of the nervous system, cell types and neural populations organized into circuits. We have developed methods to measure, manipulate, and analyze neural circuits across various spatial and temporal scales, including technology for virtual reality, optical imaging, optogenetics, intracellular electrophysiology, molecular sensors, and computational modeling. I will present recent work that uses large scale calcium imaging to reveal the functional organization of the mouse posterior cortex for flexible decision-making during spatial navigation in virtual reality. I will also discuss work that uses optogenetics and calcium imaging during a variety of decision-making tasks to highlight how cognitive experience and context greatly alter the cortical circuits necessary for navigation decisions.

My lab studies the design principles of cytoskeletal materials the drive cellular morphogenesis, with a focus on contractile machinery in adherent cells. In addition to force generation, a key feature of these materials are distributed force sensors which allow for rapid assembly, adaptation, repair and disintegration. Here I will discuss our recent identification of 18 proteins from the zyxin, paxillin, Tes and Enigma families with mechanosensitive LIM (Lin11, Isl- 1 & Mec-3) domains. We developed a screen to assess the force-dependent localization of LIM domain-containing region (LCR) from ~30 genes to the actin cytoskeleton and identified features common to their force-sensitive localization. Through in vitro reconstitution, we found that the LCR binds directly to mechanically stressed actin filaments. Moreover, the LCR from the fission yeast protein paxillin-like 1 is also mechanosensitive, suggesting force-sensitivity is highly conserved. We speculate that the evolutionary emergence of contractile F-actin machinery coincided with, or required, proteins that could report on the stresses present there to maintain homeostasis of actively stressed networks.

My lab studies the design principles of cytoskeletal materials the drive cellular morphogenesis, with a focus on contractile machinery in adherent cells. In addition to force generation, a key feature of these materials are distributed force sensors which allow for rapid assembly, adaptation, repair and disintegration. Here I will describe how optogenetic control of RhoA GTPase is a powerful and versatile force spectroscopy approach of cytoskeletal assemblies and its recent use to probe repair response in actomyosin stress fibers. I will also describe our recent identification of 18 proteins from the zyxin, paxillin, Tes and Enigma families with mechanosensitive LIM (Lin11, Isl- 1 & Mec-3) domains that bind exclusively to mechanically stressed actin filaments. Our results suggest that the evolutionary emergence of contractile F-actin machinery coincided with, or required, proteins that could report on the stresses present there to maintain homeostasis of actively stressed networks.