Short-term Effects of Vagus Nerve Stimulation on Learning and Evoked Activity in Auditory Cortex

Jesyin Lai, Stephen V. David
2021 eNeuro  
Chronic vagus nerve stimulation (VNS) has been shown to facilitate learning, but effects of acute VNS on neural coding and behavior remain less well understood. Ferrets implanted with cuff electrodes on the vagus nerve were trained by classical conditioning on an auditory tone frequency-reward association. One tone was associated with reward while another tone was not. Tone frequencies and reward associations were changed every 2 days, requiring learning of a new relationship. When tones were
more » ... ired with VNS, animals consistently learned the new association within 2 days. When VNS occurred randomly between trials, learning within 2 days was unreliable. In passively listening animals, neural activity in primary auditory cortex and pupil size were recorded before and after acute VNS-tone pairing. After pairing with a neuron's best-frequency (BF) tone, responses by a subpopulation of neurons were reduced. VNS paired with an off-BF tone or during inter-trial intervals had no effect. The BF-specific reduction in neural responses after VNS remained, even after regressing out changes explained by pupil-indexed arousal. VNS induced brief dilation in the pupil, and the size of this change predicted the magnitude of persistent changes in the neural response. This interaction suggests that fluctuations in neuromodulation associated with arousal gate the long-term VNS effects on neural activity.Significance statementVagus nerve stimulation (VNS) has been demonstrated to facilitate learning of sensory and motor behaviors. It is believed to trigger neuromodulator release that mediates cortical plasticity associated with learning. This study explores short-term VNS effects that can support long-term plasticity in the auditory cortex (A1). Just two days of VNS were adequate to support enhanced learning of an auditory discrimination task. Neural recordings from A1 revealed briefly pairing VNS with a neuron's best-frequency tone reduced responses in a subpopulation of neurons. This reduction persisted even after regressing out responses explained by pupil size, a measure of global arousal. These results support a role for VNS in auditory learning and help establish VNS as a tool to facilitate neural plasticity.
doi:10.1523/eneuro.0522-20.2021 pmid:34088737 fatcat:76aejnd6nvcq7gtfhsfbcb276y