Rebecca A. Senft

Bio: Rebecca A. Senft is an academic researcher from Harvard University. The author has contributed to research in topics: Dorsal raphe nucleus & Raphe. The author has an hindex of 5, co-authored 9 publications receiving 110 citations. Previous affiliations of Rebecca A. Senft include Howard Hughes Medical Institute & Duke University.

A single-cell transcriptomic and anatomic atlas of mouse dorsal raphe Pet1 neurons.

Abstract: Among the brainstem raphe nuclei, the dorsal raphe nucleus (DR) contains the greatest number of Pet1-lineage neurons, a predominantly serotonergic group distributed throughout DR subdomains These neurons collectively regulate diverse physiology and behavior and are often therapeutically targeted to treat affective disorders Characterizing Pet1 neuron molecular heterogeneity and relating it to anatomy is vital for understanding DR functional organization, with potential to inform therapeutic separability Here we use high-throughput and DR subdomain-targeted single-cell transcriptomics and intersectional genetic tools to map molecular and anatomical diversity of DR-Pet1 neurons We describe up to fourteen neuron subtypes, many showing biased cell body distributions across the DR We further show that P2ry1-Pet1 DR neurons - the most molecularly distinct subtype - possess unique efferent projections and electrophysiological properties These data complement and extend previous DR characterizations, combining intersectional genetics with multiple transcriptomic modalities to achieve fine-scale molecular and anatomic identification of Pet1 neuron subtypes

Best practices and tools for reporting reproducible fluorescence microscopy methods.

Abstract: Although fluorescence microscopy is ubiquitous in biomedical research, microscopy methods reporting is inconsistent and perhaps undervalued. We emphasize the importance of appropriate microscopy methods reporting and seek to educate researchers about how microscopy metadata impact data interpretation. We provide comprehensive guidelines and resources to enable accurate reporting for the most common fluorescence light microscopy modalities. We aim to improve microscopy reporting, thus improving the quality, rigor and reproducibility of image-based science. Comprehensive guidelines and resources to enable accurate reporting for the most common fluorescence light microscopy modalities are reported with the goal of improving microscopy reporting, rigor and reproducibility.

Distribution and Abundance of Glucocorticoid and Mineralocorticoid Receptors throughout the Brain of the Great Tit (Parus major)

Abstract: The glucocorticoid stress response, regulated by the hypothalamic-pituitary-adrenal (HPA) axis, enables individuals to cope with stressors through transcriptional effects in cells expressing the appropriate receptors. The two receptors that bind glucocorticoids-the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR)-are present in a variety of vertebrate tissues, but their expression in the brain is especially important. Neural receptor patterns have the potential to integrate multiple behavioral and physiological traits simultaneously, including self-regulation of glucocorticoid secretion through negative feedback processes. In the present work, we quantified the expression of GR and MR mRNA throughout the brain of a female great tit (Parus major), creating a distribution map encompassing 48 regions. This map, the first of its kind for P. major, demonstrated a widespread but not ubiquitous distribution of both receptor types. In the paraventricular nucleus of the hypothalamus (PVN) and the hippocampus (HP)-the two brain regions that we sampled from a total of 25 birds, we found high GR mRNA expression in the former and, unexpectedly, low MR mRNA in the latter. We examined the covariation of MR and GR levels in these two regions and found a strong, positive relationship between MR in the PVN and MR in the HP and a similar trend for GR across these two regions. This correlation supports the idea that hormone pleiotropy may constrain an individual's behavioral and physiological phenotype. In the female song system, we found moderate GR in hyperstriatum ventrale, pars caudalis (HVC), and moderate MR in robust nucleus of the arcopallium (RA). Understanding intra- and interspecific patterns of glucocorticoid receptor expression can inform us about the behavioral processes (e.g. song learning) that may be sensitive to stress and stimulate future hypotheses concerning the relationships between receptor expression, circulating hormone concentrations and performance traits under selection, including behavior.

Glucocorticoid-Mediated Phenotypes in Vertebrates : Multilevel Variation and Evolution

Abstract: This chapter was originally published in the book Advances in the Study of Behavior, Volume 48. The copy attached is provided by Elsevier for the author's benefit and for the benefit of the author's institution, for non-commercial research, and educational use. This includes without limitation use in instruction at your institution, distribution to specific colleagues, and providing a copy to your institution's administrator.

Dynamics of ACTH and Cortisol Secretion and Implications for Disease.

Abstract: The past decade has seen several critical advances in our understanding of hypothalamic-pituitary-adrenal (HPA) axis regulation. Homeostatic physiological circuits need to integrate multiple internal and external stimuli and provide a dynamic output appropriate for the response parameters of their target tissues. The HPA axis is an example of such a homeostatic system. Recent studies have shown that circadian rhythmicity of the major output of this system-the adrenal glucocorticoid hormones corticosterone in rodent and predominately cortisol in man-comprises varying amplitude pulses that exist due to a subhypothalamic pulse generator. Oscillating endogenous glucocorticoid signals interact with regulatory systems within individual parts of the axis including the adrenal gland itself, where a regulatory network can further modify the pulsatile release of hormone. The HPA axis output is in the form of a dynamic oscillating glucocorticoid signal that needs to be decoded at the cellular level. If the pulsatile signal is abolished by the administration of a long-acting synthetic glucocorticoid, the resulting disruption in physiological regulation has the potential to negatively impact many glucocorticoid-dependent bodily systems. Even subtle alterations to the dynamics of the system, during chronic stress or certain disease states, can potentially result in changes in functional output of multiple cells and tissues throughout the body, altering metabolic processes, behavior, affective state, and cognitive function in susceptible individuals. The recent development of a novel chronotherapy, which can deliver both circadian and ultradian patterns, provides great promise for patients on glucocorticoid treatment.

Population-scale single-cell RNA-seq profiling across dopaminergic neuron differentiation

Abstract: Studying the function of common genetic variants in primary human tissues and during development is challenging. To address this, we use an efficient multiplexing strategy to differentiate 215 human induced pluripotent stem cell (iPSC) lines toward a midbrain neural fate, including dopaminergic neurons, and use single-cell RNA sequencing (scRNA-seq) to profile over 1 million cells across three differentiation time points. The proportion of neurons produced by each cell line is highly reproducible and is predictable by robust molecular markers expressed in pluripotent cells. Expression quantitative trait loci (eQTL) were characterized at different stages of neuronal development and in response to rotenone-induced oxidative stress. Of these, 1,284 eQTL colocalize with known neurological trait risk loci, and 46% are not found in the Genotype-Tissue Expression (GTEx) catalog. Our study illustrates how coupling scRNA-seq with long-term iPSC differentiation enables mechanistic studies of human trait-associated genetic variants in otherwise inaccessible cell states.