Biology subjects

Weir, R. F.

Publications and source records attributed to Weir, R. F..

3 recordsLinked to original sources

bioRxiv2026

Multi-site temporal control of optogenetic stimulation enhances firing frequencies in peripheral nerves

We find that multi-site temporal control of optogenetic photostimulation in peripheral nerves can enhance firing rates by overcoming the intrinsic limitation of opsin photophysics. The benefits of multi-site optogenetic stimulation were demonstrated with three approaches: (1) in silico modeling, (2) ex vivo in the sciatic nerve, and (3) in vivo in the vagus nerve. An in silico model of multi-site optogenetic stimulation was developed in two Hodgkin and Huxley type neuron models, that supported our hypothesis. The ex vivo sciatic nerve showed an increase in firing frequency that is physiologically relevant for functional control. The technique was then applied in vivo for optogenetic vagus nerve stimulation resulting in significant changes in heart rate compared with standard methods of single-site stimulation. Improving the control of optogenetically induced neural firing will have broad impacts for future developments in optical nerve interfaces and brain-machine interfaces.

neuroscience↗

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↗