Identification of vagus nerve stimulation parameters affecting rat hippocampal electrophysiology without temperature effects.

BACKGROUND

Recent experiments in rats have demonstrated significant effects of VNS on hippocampal excitability but were partially attributed to hypothermia, induced by the applied VNS parameters.

OBJECTIVE

To allow meaningful preclinical research on the mechanisms of VNS and translation of rodent results to clinical VNS trials, we aimed to identify non-hypothermia inducing VNS parameters that significantly affect hippocampal excitability.

METHODS

VNS was administered in cycles of 30 s including either 0.1, 0.16, 0.25, 0.5, 1.5, 3 or 7 s of VNS ON time (biphasic pulses, 250μs/phase, 1 mA, 30 Hz) and the effect of different VNS ON times on brain temperature was evaluated. VNS paradigms with and without hypothermia were compared for their effects on hippocampal neurophysiology in freely moving rats.

RESULTS

Using VNS parameters with an ON time/OFF time of up to 0.5 s/30 s did not cause hypothermia, while clear hypothermia was detected with ON times of 1.5, 3 and 7 s/30 s. Relative to SHAM VNS, the normothermic 0.5 s VNS condition significantly decreased hippocampal EEG power and changed dentate gyrus evoked potentials with an increased field excitatory postsynaptic potential slope and a decreased population spike amplitude.

CONCLUSION

VNS can be administered in freely moving rats without causing hypothermia, while profoundly affecting hippocampal neurophysiology suggestive of reduced excitability of hippocampal neurons despite increased synaptic transmission efficiency.