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.

Vagus nerve stimulation (VNS) is a therapy on medically refractory epilepsy, and recently reported to improve cognitive function including learning and memory. The thalamo-cortical system may underlie such VNS-induced cognitive improvements. Thus, the present study targeted the auditory cortex and thalamus in rats, and investigated whether and how VNS modulates stimulus-specific adaptation (SSA) of the neural activity in these nuclei. A depth electrode array recorded auditory evoked potentials from the auditory thalamus and cortex under an oddball paradigm either with or without VNS. Consequently, VNS weakened SSA in the cortex, but did not affect that in the thalamus, indicating that VNS has neuromodulatory effects on the cortical inhibitory system and the thalamo-cortical projections, but not on the feedforward projections from the auditory periphery up to thalamus.

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The interaction between the thalamus and sensory cortex plays critical roles in sensory processing. Previous studies have revealed pathway-specific synaptic properties of thalamo-cortical connections. However, few studies to date have investigated how each pathway routes moment-to-moment information. Here, we simultaneously recorded neural activity in the auditory thalamus (or ventral division of the medial geniculate body; MGv) and primary auditory cortex (A1) with a laminar resolution in anesthetized rats. Transfer entropy (TE) was used as an information theoretic measure to operationalize “information flow”. Our analyses confirmed that communication between the thalamus and cortex was strengthened during presentation of auditory stimuli. In the resting state, thalamo-cortical communications almost disappeared, whereas intracortical communications were strengthened. The predominant source of information was the MGv at the onset of stimulus presentation and layer 5 during spontaneous activity. In turn, MGv was the major recipient of information from layer 6. TE suggested that a small but significant population of MGv-to-A1 pairs was “information-bearing,” whereas A1-to-MGv pairs typically exhibiting small effects played modulatory roles. These results highlight the capability of TE analyses to unlock novel avenues for bridging the gap between well-established anatomical knowledge of canonical microcircuits and physiological correlates via the concept of dynamic information flow.

The interaction between the thalamus and sensory cortex plays critical roles in sensory processing. Previous studies have revealed pathway-specific synaptic properties of thalamo-cortical connections. However, few studies to date have investigated how each pathway routes moment-to-moment information. Here, we simultaneously recorded neural activity in the auditory thalamus (or ventral division of the medial geniculate body; MGv) and primary auditory cortex (A1) with a laminar resolution in anesthetized rats. Transfer entropy (TE) was used as an information theoretic measure to operationalize “information flow”. Our analyses confirmed that communication between the thalamus and cortex was strengthened during presentation of auditory stimuli. In the resting state, thalamo-cortical communications almost disappeared, whereas cortico-cortical communications were strengthened. The predominant source of information was the MGv at the onset of stimulus presentation and layer 5 during spontaneous activity. In turn, MGv was the major recipient of information from layer 6. TE suggested that a small but significant population of MGv-to-A1 pairs was “information-bearing,” whereas A1-to-MGv pairs typically exhibiting small effects played modulatory roles. These results highlight the capability of TE analyses to unlock novel avenues for bridging the gap between well-established anatomical knowledge of canonical microcircuits and physiological correlates via the concept of dynamic information flow.