Biology subjects

Fontaine, A. K.

Publications and source records attributed to Fontaine, A. K..

3 recordsLinked to original sources

bioRxiv2026

Attenuation of Inflammatory Cytokines by Selective Vagal Motor Stimulation via Silicone Spiral Nerve Cuff

ObjectivesTo determine how selective optogenetic vagus nerve stimulation (VNS) of distinct axonal subpopulations modulates systemic inflammatory cytokines in an acute model of endotoxemia. Materials and MethodsA silicone spiral nerve cuff with integrated custom probes including microscale light-emitting diodes (LEDs) was fabricated and implanted on the left cervical vagus nerve of anesthetized transgenic mice expressing ChR2 under cholinergic (ChAT) or glutamatergic (Vglut2) cell promoters. Lipopolysaccharide (3 mg/kg) was administered intraperitoneally to induce endotoxemia, and mice received optical VNS for 2 hours. Blood was collected 30 minutes after VNS termination and quantified via immunoassay for serum inflammatory cytokines (IL-6, IL-1{beta}, TNF-, IL-10) and C-reactive protein (CRP). ResultsChAT-selective optical VNS significantly reduced IL-6 (p = 0.027) and IL-1{beta} (p = 0.026) relative to Cre-negative sham controls. Vglut2-targeted stimulation did not significantly reduce IL-6, IL-1{beta}, or TNF- versus sham. Cytokine levels were significantly reduced with ChAT VNS compared to Vglut2 VNS in all pro-inflammatory cytokines (IL-6: p=0.024, IL-1{beta}: p=0.011, TNF-: p=0.030). The anti-inflammatory cytokine IL-10 was significantly decreased with ChAT versus Vglut2 VNS (p=0.033). CRP levels were not statistically different between groups. ConclusionsOptogenetic VNS targeting cholinergic neurons produced robust suppression of key pro-inflammatory cytokines IL-1{beta} and IL-6, whereas stimulation of glutamatergic neurons did not significantly alter inflammatory cytokine levels, highlighting the importance of pathway selectivity in the inflammatory effects of VNS. These findings highlight cell-type specific optogenetic neuromodulation as a valuable tool for assessing impact of vagal circuits and support preferential targeting of efferent cholinergic neurons in acute systemic inflammation.

bioengineering↗

bioRxiv2020

Selective Modulation of Heart and Respiration by Optical Control of Vagus Nerve Axons Innervating the Heart

Targeting specifics subsets of peripheral pathways of the autonomic nervous system will enable new avenues to study organ control and develop new disease therapies. Vagus nerve stimulation (VNS) has shown many therapeutic benefits but current approaches involve imprecise electrical stimulation that gives rise to adverse effects, and the functionally relevant pathways are poorly understood. One method to overcome these limitations is the use of optogenetic techniques, which facilitate highly specific neural communication with light-sensitive actuators (opsins). Opsins can be targeted to cell populations of interest based on the location of viral delivery and genetic control of expression. Here, we tested whether holographic photostimulation of subsets of axons of the cervical vagus nerve that innervate the heart can be used to modulate cardiac function. Viral injection of retrograde adeno-associated virus (rAAV2-retro) in the heart resulted in robust, primarily afferent, opsin reporter expression in the vagus nerve, nodose ganglion, and brainstem. Selective holographic photostimulation of axons resulted in changes in heart rate, surface cardiac electrogram, and respiratory responses that were different from responses elicited by whole nerve photostimulation.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioengineering↗

bioRxiv2019

Optogenetic Stimulation of Pancreatic Function via Vagal Cholinergic Axons

Previous studies have demonstrated stimulation of endocrine pancreas function by vagal nerve electrical stimulation. While this increases insulin secretion; concomitant reductions in circulating glucose do not occur. A complicating factor is the non-specific nature of electrical nerve stimulation. Optogenetic tools enable high specificity in neural stimulation using cell-type specific targeting of opsins and/or spatially shaped excitation light. Here, we demonstrate light-activated stimulation of the endocrine pancreas by targeting vagal parasympathetic axons. In a mouse model expressing ChannelRhodopsin2 (ChR2) in cholinergic cells, serum insulin and glucose were measured in response to both ultrasound image-guided optical stimulation of axon terminals in the pancreas and optical stimulation of axons of the cervical vagus nerve, together with ultrasound-based measures of pancreas blood flow. Measurements were made in basal-glucose and glucose-stimulated conditions. Significant increases in plasma insulin occurred relative to controls under both pancreas and vagal stimulation, accompanying rapid reductions in glycemic levels. Additionally, a significant increase in pancreatic blood flow was measured following optical stimulation. Together, these results demonstrate the utility of in-vivo optogenetics for studying the neural regulation of endocrine pancreas function and suggest therapeutic potential for the control of insulin secretion and glucose homeostasis.

bioengineering↗