Faculty Bibliography

Reproduction is the biological process by which new individuals are produced by their parents. It is the fundamental feature of all known life and is required for the existence of all species. All mammals reproduce sexually, a process that involves the union of two reproductive cells, one from a male and one from a female. Sexual behaviors are a series of actions leading to reproduction. They are composed of appetitive, action, and refractory phases, each supported by dedicated developmentally-wired neural circuits to ensure high reproduction success. In rodents, successful reproduction can only occur during female ovulation. Thus, female sexual behavior is tightly coupled with ovarian activity, namely the estrous cycle. This is achieved through the close interaction between the female sexual behavior circuit and the hypothalamic-pituitary-gonadal (HPG) axis. In this review, we will summarize our current understanding, learned mainly in rodents, regarding the neural circuits underlying each phase of the female sexual behaviors and their interaction with the HPG axis, highlighting the gaps in our knowledge that require future investigation.

Central metabolism has a profound impact on the clinical phenotypes and penetrance of neurological diseases such as Alzheimer"™s (AD) and Parkinson"™s (PD) diseases, Amyotrophic Lateral Sclerosis (ALS) and Autism Spectrum Disorder (ASD). In contrast to the multifactorial origin of these neurological diseases, neurodevelopmental impairment and neurodegeneration in Familial Dysautonomia (FD) results from a single point mutation in the ELP1 gene. FD patients represent a well-defined population who can help us better understand the cellular networks underlying neurodegeneration, and how disease traits are affected by metabolic dysfunction, which in turn may contribute to dysregulation of the gut"“brain axis of FD. Here, ¹H NMR spectroscopy was employed to characterize the serum and fecal metabolomes of FD patients, and to assess similarities and differences in the polar metabolite profiles between FD patients and healthy relative controls. Findings from this work revealed noteworthy metabolic alterations reflected in energy (ATP) production, mitochondrial function, amino acid and nucleotide catabolism, neurosignaling molecules, and gut-microbial metabolism. These results provide further evidence for a close interconnection between metabolism, neurodegeneration, and gut microbiome dysbiosis in FD, and create an opportunity to explore whether metabolic interventions targeting the gut"“brain"“metabolism axis of FD could be used to redress or slow down the progressive neurodegeneration observed in FD patients.

Memory reactivations and replay, widely reported in the hippocampus and cortex across species, have been implicated in memory consolidation, planning, and spatial and skill learning. Technological advances in electrophysiology, calcium imaging, and human neuroimaging techniques have enabled neuroscientists to measure large-scale neural activity with increasing spatiotemporal resolution and have provided opportunities for developing robust analytic methods to identify memory replay. In this article, we first review a large body of historically important and representative memory replay studies from the animal and human literature. We then discuss our current understanding of memory replay functions in learning, planning, and memory consolidation and further discuss the progress in computational modeling that has contributed to these improvements. Next, we review past and present analytic methods for replay analyses and discuss their limitations and challenges. Finally, looking ahead, we discuss some promising analytic methods for detecting nonstereotypical, behaviorally nondecodable structures from large-scale neural recordings. We argue that seamless integration of multisite recordings, real-time replay decoding, and closed-loop manipulation experiments will be essential for delineating the role of memory replay in a wide range of cognitive and motor functions.

We present a descriptive model of choice derived from neuroscientific models of efficient value representation in the brain. Our basic model, a special case of Expected Utility Theory, can capture a number of behaviors predicted by Prospect Theory. It achieves this with only two parameters: a time-indexed "payoff expectation" (reference point) and a free parameter we call "predisposition". A simple extension of the model outside the domain of Expected Utility also captures the Allais Paradox. Our models shed new light on the computational origins and evolution of risk attitudes and aversion to outcomes below reward expectation (reference point). It delivers novel explanations of the endowment effect, the observed heterogeneity in probability weighting functions, and the Allais Paradox, all with fewer parameters and higher descriptive accuracy than Prospect Theory.

Cystinuria is the most common genetic cause of recurrent kidney stones. As the result of a genetic defect in proximal tubular reabsorption of filtered cystine, increased urine levels of the poorly soluble amino acid result in recurrent cystine nephrolithiasis. Recurrent cystine stones not only adversely affect the quality of patients suffering from cystinuria but also may result in chronic kidney disease (CKD) from recurrent renal injury. Thus, the mainstay of medical management revolves around prevention of stones. Recently published consensus statements on guidelines for managing cystinuria were released from both the United States and Europe. The purpose of this review is to summarize guidelines for medical management of patients with cystinuria, to provide new insight into the utility and clinical significance of cystine capacity"”an assay for monitoring cystinuria, and to discuss future directions for research on treatment of cystinuria. We discuss future directions, including the potential use of cystine mimetics, gene therapy, V2-receptor blockers, and SGLT2 inhibitors, topics which have not appeared in more recent reviews. It is notable that in the absence of randomized, controlled trials, the recommendations cited here and in the guidelines are based on our best understanding of the disorder"™s pathophysiology, observational studies, and clinical experience.

The neuromodulator dopamine (DA) is essential for regulating learning, motivation, and movement. Despite its importance, however, the mechanisms by which DA influences the activity of target cells to alter behavior remain poorly understood. In this review, we describe recent methodological advances that are helping to overcome challenges that have historically hindered the field. We discuss how the employment of these methods is shedding light on the complex dynamics of extracellular DA in the brain, as well as how DA signaling alters the electrical, biochemical, and population activity of target neurons in vivo. These developments are generating novel hypotheses about the mechanisms through which DA release modifies behavior.

A recent study has shown that, in the fly Drosophila, olfactory neurons stop signaling when smells get too strong. This changes the way we think about odor encoding across concentrations.

Insects use their antennae to smell odors,¹

In 2016, China launched long-term care insurance (LTCI) pilot programs in 15 cities across the country. In this Commentary, we provide an overview of these pilots regarding the target insured population, sources of financing, beneficiary eligibility criteria, and benefit design. We offer perspectives on the strengths and limitations, implementation challenges, and future prospects of these ongoing pilots. Also, we highlight the needs for addressing several key policy issues and challenges before further expanding these programs toward national implementation. These include solidifying the LTCI financing pool for independence and self-sustainability, balancing national priorities and local needs in LTCI design, reducing coverage gaps and disparities, ensuring quality of care through pay-for-performance and regulatory oversight, and strengthening independent evaluation of LTCI implementation and impacts.