Effect of low frequency stimulation of olfactory bulb and olfactory epithelium on epileptiform activity and synaptic plasticity following pentylenetetrazol administration in rats

BACKGROUND: The effect of olfactory bulb (OB) and olfactory epithelium (OE) electrical stimulation on epileptiform activity and seizure-induced impairment on synaptic plasticity and memory was investigated in anesthetized and freely-moving animals. METHODS: Male Wistar rats were anesthetized with urethane (1.5 g/kg). Stimulating electrodes were bilaterally placed in either the OB or the OE. Another electrode was placed in the CA1 area for recording epileptiform discharges (EDs) following a pentylenetetrazol (PTZ, i.v.) injection and evoked field potentials following Schaffer collateral stimulation. Subjects were divided into PTZ and control groups. Each group received a 1 Hz stimulation either in the OB (OBS) or the OE (OES). ED threshold and duration, and the ability to generate long-term potentiation (LTP) were assessed. Finally, the effect of OBS on acute PTZ-induced seizures and working memory was investigated in freely-moving animals. OBS significantly increased the ED threshold when applied at 250 µA and decreased ED duration when applied at 125 and 250 µA. RESULTS: Applying OES had a small effect on the ED threshold but significantly decreased ED duration when applied at 125 and 250 µA. Both OBS and OES mitigated the PTZ-induced increase in basal synaptic transmission. Meanwhile, OBS and OES significantly restored the LTP generation following PTZ injection in anesthetized rats. In addition, applying OBS in freely-moving animals reduced the seizure severity and restored working memory impairment. CONCLUSIONS: OB and OE may be considered effective stimulation targets for the attenuation of epileptiform activity and seizure severity. In addition, both OBS and OES decreased the seizure-induced impairment in LTP generation.