Abstract
Neuromodulation achieved by vagus nerve stimulation (VNS) induces various neuropsychiatric effects whose underlying mechanisms of action remain poorly understood. Innervation of neuromodulators and a microcircuit structure in the cerebral cortex informed the hypothesis that VNS exerts layer-specific modulation in the sensory cortex and alters the balance between feedforward and feedback pathways. To test this hypothesis, we characterized laminar profiles of auditory-evoked potentials (AEPs) in the primary auditory cortex (A1) of anesthetized rats with an array of microelectrodes and investigated the effects of VNS on AEPs and stimulus specific adaptation (SSA). VNS predominantly increased the amplitudes of AEPs in superficial layers, but this effect diminished with depth. In addition, VNS exerted a stronger modulation of the neural responses to repeated stimuli than to deviant stimuli, resulting in decreased SSA across all layers of the A1. These results may provide new insights that the VNS-induced neuropsychiatric effects may be attributable to a sensory gain mechanism: VNS strengthens the ascending input in the sensory cortex and creates an imbalance in the strength of activities between superficial and deep cortical layers, where the feedfoward and feedback pathways predominantly originate, respectively.
Highlights
Vagus nerve stimulation (VNS) that applies electric pulses to the vagus nerve at regular intervals has demonstrated therapeutic efficacy in alleviating refractory epilepsy[1,2] and depression[3,4]
The main experiments consisted of a click sequence and oddball paradigms of tone bursts, where test stimuli were presented at a rate of 1 Hz and auditory-evoked potentials (AEPs) were grand-averaged across trials in each session[53]
Investigating the effects of vagus nerve stimulation (VNS) on AEPs within the cortical layers of the A1, we found that VNS increased AEP amplitudes in the superficial layers (L1–L4) and that this effect diminished with cortical depth (L5 and L6)
Summary
Vagus nerve stimulation (VNS) that applies electric pulses to the vagus nerve at regular intervals has demonstrated therapeutic efficacy in alleviating refractory epilepsy[1,2] and depression[3,4]. The relatively denser innervation of superficial layers by NA, 5-HT and ACh nerve terminals[29,30,31,32,33,34,35,36] and the comparative abundance of DA terminals in deep cortical layers[37,38,39] informs our hypothesis that the neuromodulation of VNS is layer-specific. Such layer-specific neuromodulation might contribute to the balanced integration of bottom-up and top-down sensory inputs[40,41,42], which might underlie various neuropsychiatric effects. We propose that VNS involves a sensory gain control mechanism that enhances ascending cortical inputs
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