Science Society

Nausea is a deeply unpleasant sensation that often proves difficult to control. In this episode, we delve into the world of nausea, gut hormones, and brainstem circuits with Dr. Zhang, whose innovative research provides new insights into how our bodies handle this gut malaise.

Drawing upon a detailed cell atlas of the area postrema (a sensory circumventricular organ in the brain that detects bloodborne factors), Dr. Zhang and his team have identified inhibitory neurons that counteract nausea associated with various visceral poisons. Their findings pivot around the gut hormone glucose insulinotropic peptide (GIP), which activates area postrema inhibitory neurons. These neurons then locally project and elicit inhibitory currents in the nausea-promoting excitatory neurons via γ-aminobutyric acid (GABA) receptors.

Dr. Zhang's study further reveals that GIP can block behavioral responses to poisons in mice, but this protective effect disappears when the targeted area postrema neurons are eliminated. These groundbreaking findings provide valuable insights into the organization of nausea-associated brainstem circuits and suggest that targeting area postrema inhibitory neurons could offer a new pathway for treating nausea.

Tune in as we navigate the intriguing interplay between our gut and brain with Dr. Zhang, revealing new opportunities for nausea intervention.

Keywords: Dr. Zhang, nausea, area postrema, inhibitory neurons, glucose insulinotropic peptide (GIP), γ-aminobutyric acid (GABA) receptors, brainstem circuits, cell atlas, pharmacological target.

https://doi.org/10.1016/j.celrep.2022.110953 Ablating brainstem GIPR neurons removes anti-nausea effects of GIP

The way network activity is coordinated in the basolateral amygdala (BLA) plays a critical role in the expression of fear. While neuromodulatory systems are known to regulate shifts between behavioral states, the underlying mechanisms largely remain a mystery. Dr. Tasker joins us in this episode to discuss his recent findings which shed light on this enigmatic process.

His team used a mouse model to explore the effects of chemogenetic Gq activation and α1 adrenoreceptor activation in BLA parvalbumin (PV) interneurons. The results revealed a stereotyped phasic bursting in PV neurons and time-locked synchronized bursts of inhibitory postsynaptic currents and phasic firing in BLA principal neurons. Interestingly, this activation in PV neurons was found to suppress gamma oscillations in vivo and in an ex vivo slice model, facilitating fear memory recall. This phenomenon aligns with the observed suppression of BLA gamma during the expression of conditioned fear.

Dr. Tasker's research identifies a key neuromodulatory mechanism in PV inhibitory interneurons of the BLA, offering new insights into the regulation of BLA network oscillations and fear memory recall. Tune in as we delve into this exciting area of neuroscience research.

Keywords: Dr. Tasker, Fear Memory Recall, Network Oscillations, Basolateral Amygdala, Neuromodulatory Systems, Parvalbumin Interneurons, Gamma Suppression.

Gq neuromodulation of BLA parvalbumin interneurons induces burst firing and mediates fear-associated network and behavioral state transition in mice. (2022). https://doi.org/10.1038/s41467-022-28928-y

Cryopreservation has underpinned several scientific advancements, including assisted reproductive technology, stem cell therapies, and species preservation. However, current cryoprotective agents like dimethylsulfoxide and glycerol have notable limitations, including toxicity and inefficacy for numerous cell types and tissues. In this episode, we host Dr. Bryant, who has recently made a groundbreaking stride towards developing more effective cryoprotectants.

Dr. Bryant's team has been investigating the use of deep eutectic solvents as cryoprotective agents, and their research has provided promising results. They examined six deep eutectic solvents for their cryoprotective abilities for mammalian cells, studying their thermal properties, toxicity, and cell permeability. The researchers found a deep eutectic solvent made from proline and glycerol to be a particularly effective cryoprotective agent for all tested cell types, even with extended pre-freeze incubation.

The success of this solvent represents a significant leap forward in cryopreservation, as it exhibited less toxicity and higher effectiveness than its individual components, underlining the value of multi-component systems. The post-thaw cells were characterized using atomic force microscopy and confocal microscopy, with molecular dynamics simulations corroborating the biophysical parameters obtained experimentally.

Join us as Dr. Bryant walks us through the exciting potential of deep eutectic solvents in cryopreservation, opening doors for the development of thousands of new cryoprotective agents and potential advancements in organ and tissue preservation.

Keywords: Cryopreservation, Deep Eutectic Solvents, Dr. Bryant, Cryoprotective Agents, Proline, Glycerol, Organ Preservation, Tissue Preservation.

https://doi.org/10.1039/D2TB00573E

The ability to engineer biosensors for user-specified molecules could significantly advance numerous biological applications. In this episode, we have the privilege of hosting Dr. Whitehead, who has made strides towards a method for rapidly engineering such biosensors.

The team used PYR1, a plant abscisic acid (ABA) receptor known for its adaptable ligand-binding pocket and a requirement for ligand-induced heterodimerization, which aids in constructing sense-response functions. The researchers successfully evolved 21 sensors with sensitivities ranging from nanomolar to micromolar for various small molecules, including structurally diverse natural and synthetic cannabinoids and multiple organophosphates.

Through X-ray crystallography analysis, they revealed the mechanistic basis for new ligand recognition by an evolved cannabinoid receptor. Furthermore, the team demonstrated that the PYR1-derived receptors could be effectively ported to various ligand-responsive outputs, including ELISA-like assays, luminescence by protein-fragment complementation, and transcriptional circuits, all with picomolar to nanomolar sensitivity.

Join us as we dive into Dr. Whitehead's fascinating work with the PYR1 scaffold and how it could revolutionize the creation of new biosensors for a broad spectrum of sense-response applications.

Keywords: Biosensors, Engineering, Dr. Whitehead, PYR1, Abscisic Acid, Cannabinoids, Organophosphates, Ligand-responsive Outputs, ELISA, Protein-fragment Complementation, Transcriptional Circuits.

Beltrán, J., Steiner, P.J., Bedewitz, M. et al. Rapid biosensor development using plant hormone receptors as reprogrammable scaffolds. Nat Biotechnol (2022). https://doi.org/10.1038/s41587-022-01364-5

The multifaceted relationship between crime, policing, and society has long been a subject of controversy, particularly with the advent of artificial intelligence (AI) algorithms in crime prediction and predictive policing. In this intriguing episode, we have the pleasure of hosting Dr. Ishanu Chattopadhyay, whose work demonstrates how predictive models can do more than just enhance state power—they can offer an unprecedented insight into systemic biases in crime enforcement.

Dr. Chattopadhyay and his team introduce a novel stochastic inference algorithm that learns spatio-temporal dependencies from crime reports, allowing for impressive accuracy in crime forecasting. Yet, this breakthrough in prediction has far-reaching implications beyond law enforcement efficacy. It offers a powerful tool for social analysis, uncovering evidence of bias in the response to crime based on neighborhood socio-economic status. This can divert policy resources away from disadvantaged areas, perpetuating social inequality—an alarming trend observed across eight major US cities.

Join us as we delve into Dr. Chattopadhyay's transformative work, which stands at the intersection of advanced predictive technology and social justice. Discover how AI can be used not only as a surveillance tool for crime but also as a mirror reflecting societal biases in crime enforcement.

Keywords: Predictive Policing, Crime, Artificial Intelligence, Systemic Bias, Socio-economic Status, Surveillance, Dr. Ishanu Chattopadhyay.

Rotaru, V., Huang, Y., Li, T. et al. Event-level prediction of urban crime reveals a signature of enforcement bias in US cities. Nat Hum Behav (2022). https://doi.org/10.1038/s41562-022-01372-0

Despite glia playing a pivotal role in the pathophysiology of psychiatric and neurodegenerative disorders, current methods for imaging these cells in vivo present a myriad of limitations. In this episode, we are joined by Dr. Silvia de Santis, who introduces a game-changing, noninvasive method for imaging changes in glia morphology using diffusion-weighted magnetic resonance imaging (MRI).

Dr. De Santis and her team have validated this method in rat models of neuroinflammation, degeneration, and demyelination, demonstrating that diffusion-weighted MRI can provide insights into microglia and astrocyte activation. More importantly, this method has the sensitivity to detect changes in glia morphology and proliferation, enabling a quantitative evaluation of neuroinflammation that is independent of neuronal loss or demyelinating injury.

Extending the findings to humans, they have shown significant associations between MRI and histological microglia markers, proving the translational value of this novel approach. Join us as we explore how this groundbreaking work by Dr. De Santis can revolutionize both basic and clinical research, providing valuable insights into the role of inflammation in health and disease.

Keywords: Glia Morphology, Diffusion-weighted MRI, Neuroinflammation, Neurodegeneration, Demyelination, Microglia, Astrocyte, Noninvasive Imaging, Dr. Silvia de Santis.

Mapping microglia and astrocyte activation in vivo using diffusion MRI https://doi.org/10.1126/sciadv.abq2923 Science

The benefits of exercise in mitigating obesity, type 2 diabetes, and other cardiometabolic diseases are well-established, but the underlying molecular and cellular mechanisms remain elusive. Join us in this episode as we explore these mechanisms with Dr. Long, whose research has led to the discovery of N-lactoyl-phenylalanine (Lac-Phe), a metabolite stimulated by exercise that suppresses feeding and obesity.

Dr. Long's team found that Lac-Phe is synthesized from lactate and phenylalanine in CNDP2+ cells, including macrophages, monocytes, and other immune and epithelial cells found in various organs. In diet-induced obese mice, an increase in Lac-Phe levels reduced food intake, leading to decreased adiposity and body weight, and improved glucose homeostasis. They further discovered that ablation of Lac-Phe biosynthesis resulted in increased food intake and obesity post-exercise training.

Importantly, the research also demonstrated that circulating Lac-Phe levels rise considerably with physical activity in humans and racehorses, indicating its role as a conserved molecular effector across different mammalian species. Tune in as we delve into how Dr. Long's pioneering work could redefine our understanding of exercise's role in metabolic health.

Keywords: Exercise, Obesity, Type 2 Diabetes, N-lactoyl-phenylalanine, Metabolic Health, Dr. Long.

Li, V.L., He, Y., Contrepois, K. et al. An exercise-inducible metabolite that suppresses feeding and obesity. Nature (2022). https://doi.org/10.1038/s41586-022-04828-5

The value of Magnetoencephalography (MEG) in detecting and localizing focal interictal epileptiform discharges (IEDs) in epilepsy patients is undisputed. However, current cryogenic MEG systems present limitations, particularly for pediatric patients, due to their rigid helmet design. In this episode, we discuss these challenges and potential solutions with Dr. Feys, whose research focuses on on-scalp MEG technology using optically pumped magnetometers (OPMs).

Dr. Feys' team conducted a single-center study on school-aged children with either self-limited idiopathic or refractory focal epilepsy. The researchers compared IED detection and localization using traditional cryogenic MEG and the new on-scalp MEG method. Their results showed that the on-scalp MEG provided higher IED amplitudes, a better signal-to-noise ratio, and similar localization value, even with a limited number of sensors and scalp coverage.

Despite occasional motion artifacts from head movements, this pioneering study suggests that on-scalp MEG could alleviate the main limitations of cryogenic MEG, particularly in pediatric settings. Tune in as Dr. Feys takes us through his groundbreaking research and its potential implications for epilepsy treatment in children.

Keywords: Magnetoencephalography, Epilepsy, Pediatric Neurology, Dr. Feys, On-Scalp MEG, Optically Pumped Magnetometers, Interictal Epileptiform Discharges.

On-Scalp Optically Pumped Magnetometers versus Cryogenic Magnetoencephalography for Diagnostic Evaluation of Epilepsy in School-aged Children https://doi.org/10.1148/radiol.212453

Aggression is a common behavioral response within rival groups, and while psychological and socio-ecological factors have been studied extensively, the neuroscience behind this phenomenon still has much to uncover. Dr. Chester is at the forefront of this exploration, specifically examining the neural correlates of outgroup versus ingroup aggression.

In this episode, we delve into Dr. Chester's study which involved 35 healthy young male participants who were either current or former students of the same university. The study participants underwent functional MRI while participating in an aggression task against both an ingroup and outgroup opponent. This task involved the participants being repeatedly provoked by their opponents, followed by the opportunity to retaliate.

Dr. Chester's findings revealed that aggression towards outgroup members was associated with activity in the ventral striatum both before and after social exclusion by outgroup members. Additionally, outgroup aggression was linked to greater activity in the rostral and dorsal medial prefrontal cortex post-exclusion.

Join us as we discuss these compelling findings with Dr. Chester and explore the critical role of frontostriatal mechanisms in motivating outgroup aggression.

Keywords: Aggression, Intergroup Conflict, Functional MRI, Neuroscience, Dr. Chester, Ventral Striatum, Medial Prefrontal Cortex.

Lasko EN, Dagher AC, West SJ, Chester DS. Neural mechanisms of intergroup exclusion and retaliatory aggression. Soc Neurosci. 2022 Jun 14:1-13. doi: 10.1080/17470919.2022.2086617. PMID: 35658812.

Adolescent binge drinking has been identified as a significant risk factor for the development of psychiatric disorders later in life, including alcohol use disorder. One of the key findings of Dr. Pandey's research is the epigenetic reprogramming that occurs at the enhancer region of the immediate-early gene, activity-regulated cytoskeleton-associated protein (Arc), known as synaptic activity response element (SARE), in the amygdala of both rodents and humans following adolescent alcohol exposure.

In this episode, we discuss Dr. Pandey's fascinating research that demonstrated that the use of dCas9-P300 was able to increase histone acetylation at the Arc SARE, thus normalizing deficits in Arc expression. This led to the reduction of anxiety and excessive alcohol drinking in an adolescent alcohol exposure rat model. Conversely, the use of dCas9-KRAB increased repressive histone methylation at the Arc SARE, reduced Arc expression, and resulted in anxiety and alcohol drinking in control rats.

Join us as we dive into these important findings with Dr. Pandey and explore how epigenomic editing in the amygdala can potentially reduce adult psychopathology following adolescent alcohol exposure.

Keywords: Epigenomics, Adolescent Binge Drinking, Alcohol Use Disorder, Dr. Pandey, dCas9-P300, dCas9-KRAB, Arc SARE, Anxiety, Alcohol Drinking.

Targeted epigenomic editing ameliorates adult anxiety and excessive drinking after adolescent alcohol exposure https://doi.org/10.1126/sciadv.abn2748