Neuroecology of Alcohol Preference in Drosophila

In this review, we highlight sources of alcohols in nature, as well as the behavioral and ecological roles that these fermentation cues play in the short lifespan of Drosophila melanogaster. With a focus on neuroethology, we describe the olfactory detection of alcohol as well as ensuing neural signaling within the brain of the fly. We proceed to explain the plethora of behaviors related to alcohol, including attraction, feeding, and oviposition, as well as general effects on aggression and courtship. All of these behaviors are shaped by physiological state and social contexts. In a comparative perspective, we also discuss inter- and intraspecies differences related to alcohol tolerance and metabolism. Lastly, we provide corollaries with other dipteran and coleopteran insect species that also have olfactory systems attuned to ethanol detection and describe ecological and evolutionary directions for further studies of the natural history of alcohol and the fly.

Graded Variation In Cortical T1w/T2w Myelination During Adolescence

Myelination influences brain connectivity during sensitive periods of development by enhancing neural signaling speed and regulating synapse formation to reduce plasticity. However, in vivo studies characterizing the maturational timing of cortical myelination during human development remain scant. Here, we take advantage of recent advances in high-resolution cortical T1w/T2w myelin mapping methods, including principled correction of B1+ transmit field effects, using data from the Human Connectome Project in Development (N=628, ages 8-21) to characterize the maturational timing of myelination from childhood through early adulthood throughout the cerebral neocortex. We apply Bayesian spline models and functional latent clustering analysis to demonstrate graded variation in the rate of cortical T1w/T2w myelin growth in neocortical areas that is strongly correlated with the sensorimotor-association (S-A) axis of cortical organization reported by others. In sensorimotor areas T1w/T2w myelin starts at high levels at early ages, increases at a fast pace, and decelerates at later ages (18-21). In intermediate multimodal areas along the S-A axis, T1w/T2w myelin tends to start at intermediate levels and increase linearly at an intermediate pace. In transmodal/paralimbic association areas high along the S-A axis, T1w/T2w myelin tends to start at low levels and increase linearly at the slowest pace. These data provide evidence for graded variation along the S-A axis in the rate of cortical myelination during adolescence, which could reflect ongoing plasticity underlying the development of complex information processing and psychological functioning.Significance StatementMyelin is a lipid membrane that is essential to healthy brain function. Myelin wraps axons to increase neural signaling speed, enabling complex neuronal functioning underlying learning and cognition. Here we characterize the developmental timing of myelination across the cerebral cortex during adolescence using recent advances in non-invasive myelin mapping. Our results provide new evidence demonstrating graded variation across the cortex in the timing of myelination during adolescence, with rapid myelination in lower-order sensory areas and gradual myelination in higher-order association areas. This spatial pattern of microstructural brain development closely parallels the sensorimotor-to-association axis of cortical organization and plasticity during ontogeny.

Signal Generation, Acquisition, and Processing in Brain Machine Interfaces: A Unified Review

Brain machine interfaces (BMIs), or brain computer interfaces (BCIs), are devices that act as a medium for communications between the brain and the computer. It is an emerging field with numerous applications in domains of prosthetic devices, robotics, communication technology, gaming, education, and security. It is noted in such a multidisciplinary field, many reviews have surveyed on various focused subfields of interest, such as neural signaling, microelectrode fabrication, and signal classification algorithms. A unified review is lacking to cover and link all the relevant areas in this field. Herein, this review intends to connect on the relevant areas that circumscribe BMIs to present a unified script that may help enhance our understanding of BMIs. Specifically, this article discusses signal generation within the cortex, signal acquisition using invasive, non-invasive, or hybrid techniques, and the signal processing domain. The latest development is surveyed in this field, particularly in the last decade, with discussions regarding the challenges and possible solutions to allow swift disruption of BMI products in the commercial market.

Learning to be on time: temporal coordination of neural dynamics by activity-dependent myelination

Activity-dependent myelination is the mechanism by which myelin changes as a function of neural activity, and plays a fundamental role in brain plasticity. Mediated by structural changes in glia, activity-dependent myelination regulates axonal conduction velocity. It remains unclear how neural activity impacts myelination to orchestrate the timing of neural signaling. We developed a model of spiking neurons enhanced with neuron-glia feedback. Inspired by experimental data and use-dependent synaptic plasticity, we introduced a learning rule, called the Activity-Dependent Myelination (ADM) rule, by which conduction velocity scales with firing rates. We found that the ADM rule implements a homeostatic control mechanism that promotes and preserves synchronization. ADM-mediated plasticity was found to optimize synchrony by compensating for variability in axonal lengths by scaling conduction velocity in an axon-specific way. This property was maintained even when the network structure is altered. We further explored how external stimuli interact with the ADM rule to trigger bidirectional and reversible changes in conduction delays. These results highlight the role played by activity-dependent myelination in synchronous neural communication and brain plasticity.

Adrenergic-Angiogenic Crosstalk in Head and Neck Cancer: Mechanisms and Therapeutic Implications

Head and neck squamous cell carcinomas (HNSCC) are loco-regionally aggressive tumors that often lead to debilitating changes in appearance, speech, swallowing and respiratory function in patients. It is therefore critical to develop novel targeted treatment strategies that can effectively target multiple components within the tumor microenvironment. In this regard, there has been an increased recognition of the role of neural signaling networks as mediators of disease progression in HNSCC. Here, we summarize the current knowledge on the mechanisms of adrenergic signaling in HNSCC specifically focusing on neurovascular crosstalk and the potential of targeting the adrenergic-angiogenic axis through repurposing of FDA-approved drugs against HNSCC.

FGF21 Response Varies by Sugar Type and is Associated with Body Weight, Dietary Added Sugar, and Neural Signaling in Humans

Fibroblast growth factor 21 (FGF21) is a liver-derived hormone that regulates energy homeostasis. In humans, few studies have investigated whether FGF21 may act to suppress sugar intake and influence eating behavior, and the effects of adiposity on post-ingestive FGF21 regulation of appetite are unknown. Here, we demonstrate among two cohorts of healthy, young adults that acute oral fructose and sucrose compared to glucose lead to greater circulating FGF21. Moreover, high compared to low dietary added sugar intake is associated with greater sucrose-stimulated FGF21 among participants with healthy weight but attenuated in people with overweight and obesity. In addition, our study is the first to demonstrate associations between circulating FGF21 and neural signaling following an acute sucrose load among humans with healthy weight. Collectively, our results suggest that these potential compensatory relationships between sucrose-stimulated circulating FGF21, habitual sugar intake, and post-ingestive brain responses may be altered among adults with overweight and obesity.

Microbial colonization induces histone acetylation critical for inherited gut-germline-neural signaling

The gut-neural axis plays a critical role in the control of several physiological processes, including the communication of signals from the microbiome to the nervous system, which affects learning, memory, and behavior. However, the pathways involved in gut-neural signaling of gut-governed behaviors remain unclear. We found that the intestinal distension caused by the bacterium Pseudomonas aeruginosa induces histone H4 Lys8 acetylation (H4K8ac) in the germline of Caenorhabditis elegans, which is required for both a bacterial aversion behavior and its transmission to the next generation. We show that induction of H4K8ac in the germline is essential for bacterial aversion and that a 14-3-3 chaperone protein family member, PAR-5, is required for H4K8ac. Our findings highlight a role for H4K8ac in the germline not only in the intergenerational transmission of pathogen avoidance but also in the transmission of pathogenic cues that travel through the gut-neural axis to control the aversive behavior.

Cone mitochondria act as microlenses to enhance light delivery and confer Stiles-Crawford-like direction sensitivity

Sensory systems that efficiently transduce physical energy into neural signaling are advantageous for survival. The vertebrate retina poses a challenge to such efficiency, featuring an inverted structure with multiple neural layers through which photons must pass, risking premature absorption or scattering. Moreover, mammalian photoceptors aggregate an unusual amount of mitochondria in the ellipsoid region immediately before the light-sensitive outer segments (OS). While these mitochondria are required to support the high metabolic demands of phototransduction, it is yet unknown their impact on light transmission. Here we demonstrate via direct live-imaging and computational modeling that such tightly packed mitochondria concentrate light to enter the OS for detection. Intriguingly, this “microlens”-like feature of cone mitochondria delivers light with an angular dependence akin to the Stiles-Crawford effect, an essential visual phenomenon that improves resolution. We thus establish an unconventional optical function for cone mitochondria, energy-producing organelles, providing insight into their role in the interpretation of noninvasive optical tools for vision research and ophthalmology clinics.