Search bioRxiv⌕ Search

Biology subjects

Carson, K. E.

Publications and source records attributed to Carson, K. E..

3 recordsLinked to original sources

Asymmetric blood flow within a shared capillary network links the nucleus of the solitary tract and area postrema

The nucleus of the solitary tract (NTS) and the area postrema (AP) form a tightly coupled dorsal medullary complex that integrates visceral and humoral signals governing autonomic and cardiometabolic regulation. While their neural interconnections are well characterized, the organization and functional significance of their shared vascular network remain poorly understood. Here, we used in vivo two-photon microscopy in rats, combined with fluorescent vascular labeling and retrograde neuronal tracing, to visualize and quantify blood flow within the AP-NTS microcirculation. We identified direct capillary connections between the two regions, confirming a continuous vascular network previously inferred from ex vivo studies. Analysis of red blood cell trajectories revealed that blood flow across these junctions is predominantly unidirectional, from the NTS toward the AP. Morphometric measurements showed that AP capillaries are nearly twice the diameter of those in the NTS, implying a lower local vascular resistance and providing a structural basis for this directionality. Despite these geometric differences, capillary flow velocities were similar between regions, consistent with active regulation that maintains stable perfusion dynamics. Together, these findings uncover a previously unrecognized, functionally asymmetric vascular pathway within the dorsal medulla. By enabling the directed transfer of diffusible neurohumoral signals from the NTS to the AP, this specialized microvascular network adds a novel layer of communication between two key brainstem autonomic centers and may represent an additional mechanism for the integration of visceral and circulating information.

neuroscience↗

Perinatal High Fat Diet Exposure Alters Oxytocin and Corticotropin Releasing Factor Inputs onto Vagal Neurocircuits Controlling Gastric Motility

Perinatal high fat diet (pHFD) exposure alters the development of vagal neurocircuits that control gastrointestinal (GI) motility and reduce stress resiliency in offspring. Descending oxytocin (OXT; prototypical anti-stress peptide) and corticotropin releasing factor (CRF; prototypical stress peptide) inputs from the paraventricular nucleus (PVN) of the hypothalamus to the dorsal motor nucleus of the vagus (DMV) modulate the GI stress response. How these descending inputs, and their associated changes to GI motility and stress responses, are altered following pHFD exposure are, however, unknown. The present study used retrograde neuronal tracing experiments, in vivo recordings of gastric tone, motility, and gastric emptying rates, and in vitro electrophysiological recordings from brainstem slice preparations to investigate the hypothesis that pHFD alters descending PVN-DMV inputs and dysregulates vagal brain-gut responses to stress. Compared to controls, rats exposed to pHFD had slower gastric emptying rates and did not respond to acute stress with the expected delay in gastric emptying. Neuronal tracing experiments demonstrated that pHFD reduced the number of PVNOXT neurons that project to the DMV, but increased PVNCRF neurons. Both in vitro electrophysiology recordings of DMV neurons and in vivo recordings of gastric motility and tone demonstrated that, following pHFD, PVNCRF-DMV projections were tonically active, and that pharmacological antagonism of brainstem CRF1 receptors restored the appropriate gastric response to brainstem OXT application. These results suggest that pHFD exposure disrupts descending PVN-DMV inputs, leading to a dysregulated vagal brain-gut response to stress. Summary Figure O_FIG O_LINKSMALLFIG WIDTH=166 HEIGHT=200 SRC="FIGDIR/small/517564v3_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@7ad6acorg.highwire.dtl.DTLVardef@a3cd04org.highwire.dtl.DTLVardef@1e8dc9borg.highwire.dtl.DTLVardef@eb7c7c_HPS_FORMAT_FIGEXP M_FIG C_FIG KeypointsO_LIMaternal high fat diet exposure is associated with gastric dysregulation and stress sensitivity in offspring C_LIO_LIThe present study demonstrates that perinatal high fat diet exposure downregulates hypothalamic-vagal oxytocin (OXT) inputs but upregulates hypothalamic-vagal corticotropin releasing factor (CRF) inputs C_LIO_LIBoth in vitro and in vivo studies demonstrated that, following perinatal high fat diet, CRF receptors were tonically active at NTS-DMV synapses, and that pharmacological antagonism of these receptors restored appropriate gastric response to OXT C_LIO_LIThe current study suggests that perinatal high fat diet exposure disrupts descending PVN-DMV inputs, leading to a dysregulated vagal brain-gut response to stress. C_LI

neuroscience↗

Liver inflammation before spinal cord injury worsens neuropathology, hepatic injury, metabolic syndrome and locomotor deficits

Liver inflammation can enhance acute leukocyte recruitment to sites of central nervous system (CNS) injury. The consequences of hepatic inflammation on recovery after injury, however, are unknown. Here, we hypothesize that liver inflammation at the time of spinal cord injury (SCI) will exacerbate spinal cord pathology and impair recovery. Rats receiving SCI with concomitant liver inflammation had worse intraspinal pathology and greater locomotor deficits than rats with baseline liver inflammation. Hepatic inflammation also potentiated SCI-induced non-alcoholic steatohepatitis (NASH), endotoxemia, insulin resistance and adiposity. Circulating and cerebrospinal levels of Fetuin-A were higher in SCI rats with liver inflammation. When microinjected into intact spinal cords, Fetuin-A caused robust macrophage activation, iron accumulation and neuron loss. These studies verify that outcomes from CNS injury are worse if the liver is concomitantly inflamed and implicate Fetuin-A as a potential neuropathological mediator. These novel data suggest hepatic inflammation is a potential clinical target for improving recovery from SCI.

neuroscience↗