Biology subjects

Stornetta, D. S.

Publications and source records attributed to Stornetta, D. S..

3 recordsLinked to original sources

bioRxiv2025

Control of Blood Pressure Variability Across Behavioral States by Brainstem Adrenergic Neurons

Short-term blood pressure (BP) variability is increasingly recognized as an independent predictor of cardiovascular and cerebrovascular risk, yet the central mechanisms that govern this variability, particularly across behavioral states, remain poorly defined. In this study, we investigated the role of C1 adrenergic neurons in the rostral ventrolateral medulla (RVLMC1) in the short-term BP regulation during sleep-wake transitions and physical activity in freely behaving rats. Using genetically targeted fiber photometry, we show that RVLMC1 neurons exhibit state-dependent activity, with rapid activation during arousal from non-REM sleep, sustained activity in REM sleep, and further recruitment during physical activity. We further demonstrate that baroreflex input is essential for the dynamic response of RVLMC1 neurons to pharmacological manipulations of BP and transitions to REM sleep. Strikingly, selective ablation of RVLMC1 neurons did not affect mean BP but caused pronounced instability during arousal and movement, underscoring their role in buffering BP fluctuations. These findings demonstrate that RVLMC1 neurons integrate arousal-related central drive with baroreceptor feedback to stabilize BP during changes in behavioral state. These findings suggest that the disruption of RVLMC1 neurons could underlie increased BP variability observed in pathological conditions, such as multiple system atrophy, even when mean BP is preserved.

neuroscience↗

bioRxiv2023

Molecular Disambiguation of Heart Rate Control by the Nucleus Ambiguus

The nucleus ambiguus (nAmb) provides parasympathetic control of cardiorespiratory functions as well as motor control of the upper airways and esophagus. A subset of nAmb neurons innervates the heart through the vagus nerve to control cardiac function at rest and during key autonomic reflexes such as the mammalian diving reflex. Yet, how these cardiovagal nAmb neurons differ from other nAmb neurons in the adult brain remains unclear. We therefore classified adult mouse nAmb neurons molecularly, anatomically, and functionally. First, our integrated analysis of single-nucleus RNA-sequencing data predicted multiple molecular subtypes of nAmb neurons. Mapping the axon projections of one nAmb neuron subtype, Npy2r-expressing nAmb neurons, showed that they innervate cardiac ganglia but not the upper airways or esophagus. Chemogenetically stimulating Npy2r+ nAmb neurons robustly decreased heart rate through peripheral muscarinic acetylcholine receptors. Finally, Npy2r+ nAmb neurons are activated during voluntary underwater diving, consistent with a cardiovagal function for this nAmb subtype. These results together reveal the molecular organization of nAmb neurons and its control of heart rate.

neuroscience↗

bioRxiv2023

Molecular organization of autonomic, respiratory, and spinally-projecting neurons in the mouse ventrolateral medulla

The ventrolateral medulla (VLM) is a crucial region in the brain for visceral and somatic control. It also serves as a significant source of synaptic input to the spinal cord. Experimental studies have shown that gene expression in individual VLM neurons is predictive of their function. However, the organizing principles of the VLM have remained uncertain. This study aimed to create a comprehensive dataset of VLM cells using single-cell RNA sequencing. The dataset was enriched with targeted sequencing of spinally-projecting and adrenergic/noradrenergic VLM neurons. Based on differentially expressed genes, the resulting dataset of 114,805 VLM cells identifies 23 subtypes of neurons, excluding those in the inferior olive, and 5 subtypes of astrocytes. Spinally-projecting neurons were found to be abundant in 7 subtypes of neurons, which were validated through in-situ hybridization. These subtypes included adrenergic/noradrenergic neurons, serotonergic neurons, and neurons expressing gene markers associated with pre-motor neurons in the ventromedial medulla. Further analysis of adrenergic/noradrenergic neurons and serotonergic neurons identified 9 and 6 subtypes, respectively, within each class of monoaminergic neurons. Marker genes that identify the neural network responsible for breathing were concentrated in 2 subtypes of neurons, delineated from each other by markers for excitatory and inhibitory neurons. These datasets are available for public download and for analysis with a user-friendly interface. Collectively, this study provides a fine-scale molecular identification of cells in the VLM, forming the foundation for a better understanding of the VLMs role in vital functions and motor control.

neuroscience↗