Fiber-based Probes for Electrophysiology, Photometry, Optical and Electrical Stimulation, Drug Delivery, and Fast-Scan Cyclic Voltammetry In Vivo.

Recording and modulation of neuronal activity enables the study of brain function in health and disease. While translational neuroscience relies on electrical recording and modulation techniques, mechanistic studies in rodent models leverage genetic precision of optical methods, such as optogenetics and imaging of fluorescent indicators. In addition to electrical signal transduction, neurons produce and receive diverse chemical signals which motivate tools to probe and modulate neurochemistry. Although the past decade has delivered a wealth of technologies for electrophysiology, optogenetics, chemical sensing, and optical recording, combining these modalities within a single platform remains challenging. This work leverages materials selection and convergence fiber drawing to permit neural recording, electrical stimulation, optogenetics, fiber photometry, drug and gene delivery, and voltammetric recording of neurotransmitters within individual fibers. Composed of polymers and non-magnetic carbon-based conductors, these fibers are compatible with magnetic resonance imaging, enabling concurrent stimulation and whole-brain monitoring. Their utility is demonstrated in studies of the mesolimbic reward pathway by simultaneously interfacing with the ventral tegmental area and nucleus accumbens in mice and characterizing the neurophysiological effects of a stimulant drug. This study highlights the potential of these fibers to probe electrical, optical, and chemical signaling across multiple brain regions in both mechanistic and translational studies.

Identifying Risk Factors for Blindness From Glaucoma at First Presentation to a Tertiary Clinic.

PURPOSE: Glaucoma is the leading cause of irreversible blindness, a crippling disability resulting in higher risks of chronic health conditions. To better understand disparities in blindness risk, we identified risk factors of blindness on first presentation to a glaucoma clinic using a large clinical database. DESIGN: Retrospective cross-sectional study. METHODS: We used electronic health records of glaucoma patients from the Duke Ophthalmic Registry. International Classification of Diseases codes were used to identify glaucoma and exclude concurrent diseases. Blindness classification was based on the definition of legal blindness. Risk factors included gender, race, marital status, age, intraocular pressure, diabetes history, income level, and education. Odds ratios (ORs) and 95% CIs were calculated for risk factors using univariable and multivariable logistic regression. RESULTS: Our cohort consisted of 3753 patients, with 192 (5%) blind on first presentation. In univariable models, African American / Black race (OR 2.48, 95% CI 1.83-3.36), single marital status (1.74, 95% CI 1.25-2.44), prior diabetes diagnosis (2.23, 95% CI 1.52-3.27), and higher intraocular pressure (1.29 per 1 SD higher, 95% CI 1.13-1.46) were associated with increased risk of presenting blind, whereas higher annual income (0.75, 95% CI 0.65-0.86) and education (0.77, 95% CI 0.69-0.85) were associated with lower risk. These associations remained significant and in the same direction in a multivariable model apart from income, which became insignificant. CONCLUSIONS: Using a large real-world clinical database, we identified risk factors associated with presentation with blindness among glaucoma patients. Our results highlight disparities in health care outcomes and indicate the importance of targeted education to reduce disparities in blindness.

A dopamine-gated learning circuit underpins reproductive state-dependent odor preference in Drosophila females.

Motherhood induces a drastic, sometimes long-lasting, change in internal state and behavior in many female animals. How a change in reproductive state or the discrete event of mating modulates specific female behaviors is still incompletely understood. Using calcium imaging of the whole brain of Drosophila females, we find that mating does not induce a global change in brain activity. Instead, mating modulates the pheromone response of dopaminergic neurons innervating the fly's learning and memory center, the mushroom body (MB). Using the mating-induced increased attraction to the odor of important nutrients, polyamines, we show that disruption of the female fly's ability to smell, for instance the pheromone cVA, during mating leads to a reduction in polyamine preference for days later indicating that the odor environment at mating lastingly influences female perception and choice behavior. Moreover, dopaminergic neurons including innervation of the ß'1 compartment are sufficient to induce the lasting behavioral increase in polyamine preference. We further show that MB output neurons (MBON) of the ß'1 compartment are activated by pheromone odor and their activity during mating bidirectionally modulates preference behavior in mated and virgin females. Their activity is not required, however, for the expression of polyamine attraction. Instead, inhibition of another type of MBON innervating the ß'2 compartment enables expression of high odor attraction. In addition, the response of a lateral horn (LH) neuron, AD1b2, which output is required for the expression of polyamine attraction, shows a modulated polyamine response after mating. Taken together, our data in the fly suggests that mating-related sensory experience regulates female odor perception and expression of choice behavior through a dopamine-gated learning circuit.