Pairing tone trains with vagus nerve stimulation induces temporal plasticity in auditory cortex

The selectivity of neurons in sensory cortex can be modified by pairing neuromodulator release with sensory stimulation. Repeated pairing of electrical stimulation of the cholinergic nucleus basalis, for example, induces input specific plasticity in primary auditory cortex (A1). Pairing nucleus basalis stimulation (NBS) with a tone increases the number of A1 neurons that respond to the paired tone frequency. Pairing NBS with fast or slow tone trains can respectively increase or decrease the ability of A1 neurons to respond to rapidly presented tones. Pairing vagus nerve stimulation (VNS) with a single tone alters spectral tuning in the same way as NBS-tone pairing without the need for brain surgery. In this study, we tested whether pairing VNS with tone trains can change the temporal response properties of A1 neurons. In naïve rats, A1 neurons respond strongly to tones repeated at rates up to 10 pulses per second (pps). Repeatedly pairing VNS with 15 pps tone trains increased the temporal following capacity of A1 neurons and repeatedly pairing VNS with 5 pps tone trains decreased the temporal following capacity of A1 neurons. Pairing VNS with tone trains did not alter the frequency selectivity or tonotopic organization of auditory cortex neurons. Since VNS is well tolerated by patients, VNS-tone train pairing represents a viable method to direct temporal plasticity in a variety of human conditions associated with temporal processing deficits.