Vagus nerve stimulation induces widespread cortical and behavioral activation
| Autor: | Paul J. Steffan, Lindsay Collins, David A. McCormick, Laura J. Boddington |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Vagus Nerve Stimulation medicine.medical_treatment Biology Somatosensory system General Biochemistry Genetics and Molecular Biology Mice Norepinephrine 03 medical and health sciences 0302 clinical medicine Calcium imaging Cortex (anatomy) Neuromodulation medicine Animals Cerebral Cortex Neuronal Plasticity Acetylcholine Electrophysiology 030104 developmental biology medicine.anatomical_structure Excitatory postsynaptic potential Cholinergic Calcium Female Arousal General Agricultural and Biological Sciences Neuroscience 030217 neurology & neurosurgery Vagus nerve stimulation |
| Zdroj: | Current Biology. 31:2088-2098.e3 |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/j.cub.2021.02.049 |
| Popis: | Vagus nerve stimulation (VNS) is used for management of a variety of neurological conditions, although the therapeutic mechanisms are not fully understood. Accumulating evidence suggests that VNS may modulate cortical state and plasticity through activation of broadly projecting neuromodulatory systems. Using a mouse model, we compared arousal-linked behaviors with dorsal cortical activity obtained with widefield and two-photon GCaMP6s calcium imaging and electrophysiological recordings. We observed robust and reliable cortical and behavioral dose-dependent activation in waking mice to VNS, including pupil dilation and, frequently, whisker movements and locomotion. Widefield calcium imaging and multiunit recording during VNS revealed that this observed increase in arousal state is coupled with a rapid and widespread increase in excitatory activity, including, but not limited to, activation of somatosensory, visual, motor, retrosplenial, and auditory cortical regions. Two-photon GCaMP6s calcium imaging of cholinergic and noradrenergic cortical axons revealed that VNS strongly activates these neuromodulatory systems. Importantly, VNS-evoked activation of neuromodulatory axons and excitatory neurons in the cortex persisted in mice under light anesthesia, in the absence of overt movement. Arousal state changes were abolished by vagus nerve transection, confirming that observed VNS effects were specific to nerve stimulation and triggered widespread activity above that which can be explained by motor activity. Taken together, our results support a model of VNS in which activation of subcortical structures leads to widespread activation of cortex and an increase in arousal state, at least partially due to the activation of cholinergic and noradrenergic modulatory pathways. |
| Databáze: | OpenAIRE |
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